MANUAL OF PEDIATRIC NEPHROLOGY

2nd Edition
2002
For Residents in the DM Paediatric Program
UWI

Maolynne Miller

To: The Residents

This manual, like the first edition (1988), is dedicated to the hardworking residents in the
DM Paediatrics programme who have been my inspiration throughout the years. I hope it
will be helpful to them in their preparation for paediatric practice, especially in territories
which have no paediatric nephrology services.
I wish to thank the residents who helped with this manual, in particular Dr. Klaas
Wierenga whose computer expertise was indispensable, and Dr. Young who
painstakingly graduated the peritoneal dialysis bags.
This manual has been prepared as a printed record of paediatric nephrology lectures
given over the last two years, and is not intended for commercial distribution. Any cost
affixed to the manual is solely to cover the printing expenses, and not for personal profit.
Every attempt has been made to avoid any errors, but in spite of this, it is possible that
some may have occurred. If any aberrations are noted, please check other references and
bring the matter to the authors attention.
Thank you.
Maolynne Miller. M.B.B.S., F.R.C.P.(C).
January 2002

TABLE OF CONTENTS

Chapter

Title

Start page

Assessment of renal function

Red urine and haematuria

19

Proteinuria

23

Acute glomerulonephritis

27

Nephrotic syndrome

33

Disorders of water and electrolyte balance

38

Urolithiasis and disorders of calcium balance

50

Urinary tract infections

57

Enuresis and other voiding disorders

62

10

Acute renal failure

71

11

Acute peritoneal dialysis

83

12

Chronic renal failure

89

13

Hypertension

95

14

Disorders of acid base balance

106

CHAPTER 1
ASSESSMENT OF RENAL FUNCTION
GLOMERULAR:
Fluid balance : fluid balance, edema
Filtration : wastes - urea, creatinine, creatinine clearance, electrolytes
water - edema, dilutional hyponatremia - electrolytes, specific gravity, osmolality
red cells - urine microscopy
protein - spot urine protein/creatinine, 24 hour urine protein
urinalysis - Labstix/ Uristix - sulfosalycilic acid
Radiology
TUBULAR:
Urine concentrating ability - specific gravity, osmolality
Acid/base balance - urine pH, serum bicarbonate, blood gases
Electrolyte and calcium balance - Na, K,Cl, PO4,Ca - blood and urine
+/- alkaline phosphatase(Alk.phos), serum albumin
ENDOCRINE:
1- hydroxylation of 25 OH vitamin D - Ca, PO4, Alk. phos, albumin
- X ray ( L) wrist - bone age
- X ray (L) hand - penetrated view for renal osteodystrophy
Renin - Blood pressure, electrolytes, plasma renin activity
Erythropoietin - Hb, reticulocyte count
**************************************
HISTORY:
Growth, haematuria, oedema, urinary stream, dysuria, oliguria;
Family history, syndromes
EXAMINATION:
Mucous membranes, growth parameters, edema, blood pressure, abdominal organomegaly, genital
anomalies.
URINE:
Appearance
Pale to dark yellow (normal), red (blood or beets), green (bilirubin), brown or black (old blood or
myoglobin), purple (porphyria).
Salmon coloured powder on diaper (amorphous urates), frothy
(proteinuria), clear and colourless (dilute urine).
Microscopy (see Figure 1)
Uncentrifuged - low power (X 40), and high power (X 500), for epithelial cells, WBC, bacteria, RBC (if
haematuria gross).
Centrifuged - best for RBC, casts, WBC. Ideally 10 - 15 mls freshly voided urine centrifuged at 2000 rpm
for 5 minutes. Invert the tube to remove supernatant and examine residual sediment on a glass slide.
Normal microscopy < 5 rbc/high power field (HPF)
< 5 wbc/ HPF
Hyaline casts and assorted crystals

Figure 1 Microscopic urinary findings

Urine concentrating ability Best assessed on first voided morning urine sample after an overnight fast. Urine should be voided before
retiring the previous night.
Tested by - urine osmolality (UOsm) and urine specific gravity (Usg).
a) Urine osmolality (measured by freezing point depression method).
Normal maximal urine osmolality
(max UOsm)
Age
Max UOsm (mOsm/kg H2O)
Neonate
600 - 700
Child or adult
800 - 1200
Calculate UOsm from Usg as follows:
UOsm = (Usg - 1.000) X 40,000 mOsm/kg H2O
Serum Osm = (2 serum Na) + glucose (mmol/l) + urea (mmol/l)
Hospital for Sick Children Residents Handbook of Pediatrics (1987), 7th edition, p 130. Abelson and Smith
b) USG
Measured by a) refractometer (1 drop of urine) or b) hygrometer (several mls of urine).
Less accurate but more convenient than UOsm. Falsely elevated by - high molecular weight substances
e.g. glucose, protein, radio opaque dyes and mannitol
1 gm glucose/dl in urine - increases USG by .003
1 gm protein/dl in urine - increases USG by .003

In chronic renal failure

In diabetes insipidus

USG = 1.010 (UOsm 300mOsm/kg H 0)

USG < 1.005

URINALYSIS
PROTEIN may be detected - qualitatively by - dipstix (Albustix , Labstix) or
- 3% Sulfosalicylic acid
quantitatively by - timed urine collection
- spot urine protein/creatinine ratio
Dipstix - colour change reflects protein content of urine. i.e. yellow (no protein) to dark green (4+
proteinuria). False positive - alkaline urine. False negative - dilute urine.
3% Sulfosalicylic acid(SSA) method:
Add 0.5ml 3% SSA to 0.5 ml urine in a test tube. The resultant turbidity reflects degree of proteinuria
(see below). False positives - concentrated urine, penicillin, gantrisin, cephalosporins, p Amino -salicylic
acid.
_____________________________________________________________________________
Urine
Reaction
Interpretation
Protein concentration (g/l)
(place print behind test tube)
_____________________________________________________________________________
<5
clear
negative
5 - 10

very faint turbidity-(coconut water)

can read print

trace

10 - 30

turbid - can see line only

1+

30 - 100

white cloud - can't see line

2+

white cloud with fine precipitate

3+

100 - 500

> 500
flocculent precipitate
4+
_____________________________________________________________________________
For home monitoring by out patients - cloudy urine = significant proteinuria (> 2+), and may herald a
relapse of nephrotic syndrome. Clear urine = trace/ negative proteinuria. Proteinuria < 1+ is normal.
BLOOD - may be detected by urine microscopy (only reliable method) and suggested by the Hemastix.
Hemastix also tests positive for blood with myoglobinuria or hemoglobinuria .
pH - determined on a fresh urine sample by dipstix method (accuracy of +/- 0.5 pH units) or by pH
meter on special arrangement with Chemical Pathology (more accurate).
REDUCING SUBSTANCES - not usually present in urine
Clinistix or Dipstix - positive for glucose. Clinitest method - positive for all reducing sugars glucose, galactose, fructose, lactose and other non glucose reducing substances.
Clinitest method - 2 drops urine to 10 drops water, then add clinitest tablet. Colour depends on amount
of reducing substance present.
Colour
[Glucose]
Colour
[Glucose]
blue
blue - green
green

- negative
- trace
- 0.5%

green - brown
yellow
yellow - orange
orange

- 1%
- 2%
- 3%
- 5%

24 HOUR URINE COLLECTIONS

To assess completeness of the collection, always measure on the same collection, the 24-hour creatinine
excretion.
24 hr urine CREATININE = 135 - 175 mol/kg/dy (adult female or child)
= 175 - 220 mol/kg/dy (adult male)
IF RESULT IS < THE ABOVE VALUES, THE COLLECTION IS INCOMPLETE AND THE RESULTS
THEREFORE UNRELIABLE
CREATININE CLEARANCE AND GLOMERULAR FILRATION RATE (GFR) - Both are
indices of glomerular function
Creatinine Clearance (CCr) - measured
-based on timed urine collection ( usually 24 hours )
- may be falsely high when renal function markedly reduced as creatinine secretion occurs
-fairly good measure of GFR if collection complete
Calculation of CCr (from 24 hr urine)
CCr =
uCr X V X 1.73
pCr X t
SA
uCr
pCr
V
t
SA

=
=
=
=
=

= mls/min/1.73 m2

urine concentration of Creatinine (mol/l)

serum concentration of Creatinine (mol/l)
urine volume in timed interval (usually 24 hrs) (ml)
time of collection of urine (24 hr = 1440 mins) (min)
surface area derived from height and weight

ESTIMATED GFR * - from plasma creatinine, and height

GFR
= Ht (cm)
X k
(ml/min/1.73m2)
pCr(mol/l) X .0113
GFR
pCr
k
from

Ht
= height (cm)
= glomerular filtration rate (ml/mim/1.73m2)
= plasma or serum creatinine (mol/l)
= constant of proportionality , a function of urinary creatinine per unit of body size ; may vary
the mean in malnutrition or obesity

Mean k* values at different ages

Age group
(years)
k
low birth weight infants
< 1yr
0.33
full term infants
< 1yr
0.45
children
2-12
0.55
females
13 -21
0.55
males
13-21
0.70
____________________________________________________
*From "The use of plasma creatinine concentration for estimating glomerular filtration rate in infants,
children and adolescents" Pediatric Clinics of North America (1987 ) 34 : 582
CREATININE CLEARANCE (cCr) FROM LABORATORY VALUES
Laboratory units are mls/min
Convert to mls/min/1.73m2 as follows :
cCr = (mls/min) X 1.73
= mls/min/1.73m2
2
body surface area (m )

NORMAL CREATININE CLEARANCE FOR AGE > 2 YEARS SHOULD BE > 90 ml/min/1.73m2
NORMAL SERUM CREATININE (mol/l) for age over 5 years = (< age in years X 10)
For age < 5 years = < 50mol/l
NORMAL GFR AT DIFFERENT AGES ADJUSTED TO 1.73 m2
Age
GFR(ml/min/1.73m2 )
Range (+/- 2SD)
Premature
47
29 -65
2-8 days
38
26-40
4-28 days
48
28-68
35-95 days
58
30-86
1-5.9 months
77
41-103
6-11.9 months
103
49 -157
12-19 months
127
63 - 191
2-12 years
127
89 -165
Adult males
131
88 -174
Adult females
117
87 -147
________________________________________________________________________
From Pediatric Nephrology (Page 288, 1987 Edition), Holliday, Barratt, Vernier -Editors; Williams and
Wilkins -Publishers.
NORMAL 24 HOUR URINE VOLUME
(usually 2 -2.5 ml/kg/hr)
Age
Volume (mls)
1 - 2 days
30 -60
3 - 10days
100 -300
10 - 28 days
250 -450
2mo - 1 year
400 -500
1 - 3 years
500 -600
3 - 5 years
600 -700
5 - 8 years
650 -1000
8 - 14 years
800 1400

Bladder data:
Bladder capacity (mls)
Children < 2 years : bladder capacity (ml) = 7 X weight (kg)
Children 2 11 years : bladder capacity (mls) = (age (years) + 2 X 30)
(Urology 21:248, 1983 From Urological Clinics of North America, 1995, 22: 205 219)
or bladder capacity = (age years +2 ) ounces
Residual volumes:
Age < 1 year usually 5 10 mils
School children usually < 5 mls
(J Urol 1989; 141: 916 917, Scan J Urol 1976; 37 (Suppl): 1- 106 - From Ped Nephrology 1999 edtn.)
Water losses with fever:
Fever increases water loss by 7mls / kg/day for each oF rise in temperature above 99oF , or
10 ml/kg/day for each oC rise above normal (37 oC)

Spot urine protein/ creatinine:

Protein (mg/l X .1)
Urine creatinine (mol/l) X0.0113

= mg/dl
= mg/dl

Normal
< 0.2
Moderate proteinuria 0.51 2.0

Minimal proteinuria 0.21 0.5

Nephrotic range
> 2.0

Tubular reabsorption of phosphate = 1 - [U / P phos mmol/l ]

x100%
[U/P creatinine mol/l]
Normal > 80 %
Low values suggest secondary hyperparathyroidism
Spot urine electrolyte values
Spot urine Na and K values should be interpreted in relation to serum values. Spot urine Na and K should be
< 5 10 mmol in the face of hyponatremia and hypokalemia respectively. If spot urinary losses exceed this,
suspect the kidney as being the source of the serum abnormality.
Normal solute / creatinine ratios
Calcium(mmol/l): creatinine(mol/l)= <.00074
Uric acid(mmol/l):creatinine(mol/l)= <.00067

If increased = hypercalciuria
If increased = hyperuricosuria

For normal 24 -hr urinary solute excretion see Chapter 7

24 urine phosphate

3.87 6.46

Transtubular potassium gradient (TTKG) - mineralocorticoid effect

TTKG = UK // U/ P Osm
SK
SK (serum potassium) (mmol/l)
U Osm urine osmolality (mOsm/kg H20)
POsm - plasma osmolality (mOsm/kg H2O)
> 6
< 4.9 (infant)
< 4.0 (child)

= mineralocorticoid effect
= reduced mineralocorticoid effect
= reduced mineralocorticoid effect

RENAL IMAGING
Renal ultrasonography
Assessment of renal anatomy measurement of renal size, detection of obstruction, cysts, renal or perinephric
abscesses. Hyperechogenicity suggests renal parenchymal disease. Advantage- no radiation.
Disadvantage -Is not sensitive for the detection of pyelonephritis, renal scarring and cannot reliably exclude
vesico-ureteric reflux VUR. Ask for renal measurements and compare with normal values (see below). For
premature infants request transverse renal measurements as well.
Normal renal lengths vs age Table 1
Normal renal lengths vs age, weight, height and BSA Figure 1
Normal renal measurements transverse diameter for premature infants (Table 2)

10

Table 1.

AGE-RELATED MEAN RENAL LENGTHS BY ULTRASONOGRAPHY

Adapted from: American Journal of Roentgenology 142: March, 1983

Average age*
0 mo
2 mo
6 mo
10 mo
1 1/2
2 1/2
3 1/2
4 1/2
5 1/2
6 1/2
7 1/2
8 1/2
9 1/2
10 1/2
11 1/2
12 1/2
13 1/2
14 1/2
15 1/2
16 1/2
17 1/2
18 1/2
* Years unless specified otherwise

Interval*
0-1 wk
1wk-4 mo
4 -8 mo
8mo-1 yr
1-2
2-3
3-4
4-5
5-6
6-7
7-8
8-9
9-10
10-11
11-12
12-13
13-14
14-15
15-16
16-17
17-18
18-19

Mean Renal Length

(cm)
4.48
5.28
6.15
6.23
6.65
7.36
7.36
7.87
8.09
7.83
8.33
8.90
9.20
9.17
9.60
10.42
9.79
10.05
10.93
10.04
10.53
10.81

SD**
0.31
.66
.67
.63
.54
.54
.64
.50
.54
.72
.51
.88
.90
.82
.64
.87
.75
.62
.76
.86
.29
1.13
** +/- 2SD is normal

11

Figure 1 - Normal renal lengths versus age, weight, height and BSA

From: Han BK & Babcock DS. Sonographic Measurements and Appearance of normal kidneys in
children. AJR (1985) 145:611-6

12

Table 2 - Fetal kidney by gestational age group in normal fetuses

Gestational
Age
(wk)

Fetal kidney
measurements
anteroposterior (cm)

Fetal kidney
measurements
transverse (cm)

Fetal kidney
measurements
circumference (cm)

Mean (SD)

Mean (SD)

Mean (SD)

<16
(n=9)

0.84 (0.24)

0.86 (0.14)

2.79 (0.64)

17-20
(n=18)

1.16 (0.24)

1.13 (0.25)

3.80 (0.72)

21-25
(n=7)

1.49 (0.37)

1.64 (0.40)

5.40 (0.68)

26 30
(n=11)

1.93 (0.19)

2.00 (0.28)

6.58 (0.67)

31 35
(n=19)

2.20 (0.32)

2.34 (0.42)

7.86 (0.86)

>36
(n=25)

2.32 (0.32)

2.63 (0.50)

8.42 (1.39)

Adapted from American Journal of Obstetrics and Gynaecology (1980) Vol 136: 253
Assessment of fetal kidney size in normal gestation by comparison of ratio of kidney circumference to
abdominal circumference (Grannum, Bracken, Silverman, Hobbins)

Nuclear scanning
1. Detection of acute pyelonephritis, renal scarring 99mTc DMSA, Glucoheptonate
2. Assessment of renal function and differential renal function 99m Tc DTPA and glucoheptonate, 51
Cr EDTA scan, 99m Tc MAG3
3. Differentiation of obstructive from non obstructive uropathy diuretic renography DTPA and
glucoheptonate
4. Detection of vesico- ureteric reflux direct and indirect cystography
5. Screening test for renal artery stenosis (Captopril enhanced renography) see Chapter 13
(Hypertension)
Types of nuclear scans:
1. 99m Tc DTPA - 99m Technetium labeled diaminotetraethyl pentacetic acid (DTPA) determine renal
morphology and GFR
2. 99m Technetium labeled dimercaptosuccinic acid (DMSA) scan detect renal scarring
3. 99m Tc Glucoheptonate renal scan detect renal scarring and assess renal function
4. 51 Cr EDTA scan determine GFR
5. 123 I OHI iodine labeled orthoiodohippurate measures renal plasma flow excellent renal imaging
6. 99m Tc MAG3 Technetium labeled mercapto acetyl glycylglycine measures effective renal plasma
flow (ERPF) (the proportion of the renal plasma flow presented to the renal secretory tissue) and
renal function - excellent renal imaging expensive.

13

Diagnosis and imaging of acute pyelonephritis (AP) and renal scarring - DMSA or glucoheptonate
scans:
After IV injection 99m Tc-DMSA is taken up by the tubular cells in the cortex. Uptake of DMSA is
dependent on blood flow and intact tubular cell function. AP causes local ischaemia and tubular
dysfunction, so involved areas have decreased uptake of the DMSA.
AP- focal, multifocal, or diffuse areas of decreased tracer uptake in the kidney without volume loss.
Scarring - areas of decreased uptake with volume loss.
Cortical scintigraphy should be performed in children with febrile UTI or those in whom AP is a
possibility, even if there is no demonstrable reflux on the cystogram.
Contrast enhanced computed tomography (CT)1. Diagnose acute pyelonephritis low areas of attenuation in the kidney.
2. CT delineates the perinephric space, and is the study of choice in suspected renal or perinephric abscess
(though ultrasound helpful)
3. Diagnose mass lesions / trauma to kidney
4. Can also assess renal function, but iodinated contrast required allergic risk.
CYSTOGRAPHY
Type of cystograms:
1. Fluoroscopic voiding/ micturating contrast radiography (VCUG / MCUG)
2. Radionucleide (isotope) cystogram (RNC).
MCUG - - very good anatomical resolution highly detailed images of bladder and urethra. Urethral
imaging essential in boys to exclude posterior urethral valves, detect bladder wall abnormalities eg
trabeculation, diverticula, and ureterocoeles. accurate grading of reflux using the International
Classification I- V.
1. Boys - first time work up of UTI urethral evaluation
2. Patients with history of voiding dysfunction to evaluate bladder function
Radionucleide cystography
1. Very sensitive for detection of reflux, because the entire bladder cycle from filling to after voiding is
continuously monitored.
2. Lower spatial resolution than the MCUG so bladder wall abnormalities may be missed. In addition, the
urethra cannot be evaluated.
3. Advantage - lower radiation.
4. Post op follow - up and for screening of asymptomatic siblings of patients with VUR (male or female)
5. Possibly for initial evaluation of girls with UTI because urethral anomalies are rare and significant
bladder wall abnormalities may be detected on ultrasonography.
Indirect nuclear cystography
1. Observed on voiding at the end of the DMSA or glucoheptonate scan.
2. More sensitive than voiding cystography and direct radionucleide cystography in detection of
VUR.
3. Can only be preformed in children who can void on request
Direct nuclear cystography
1. Less radiation than the standard fluoroscopic MCUG.
2. Use for follow up of VUR

14

Timing of cystography
After antibiotic therapy has begun and the urine is sterile. It is not necessary to wait a prolonged period
after treatment. In patients with dysuria or other cystitis symptoms, wait until asymptomatic so adequate
bladder filling may occur. Underfilling of the bladder may result in a false negative result for VUR.
Diuretic renography (DR) (request renal glucoheptonate scan with Lasix)
1. Imaging modality used to differentiate obstructive from non obstructive hydronephrosis / hydroureter
(H/H)
2. Performed using 99m Tc- DTPA or 99m TC MAG3 or glucoheptonate. After injection of the agent
sequential images of the kidney are obtained. Following excretion and maximal filling of the dilated
collecting system or ureter with radioactive tracer, furosemide is injected intravenously (1mg/kg) and
imaging continues. Differential renal function is calculated. The drainage pattern of each kidney is
interpreted using the images and washout half times calculated from computer- generated furosemide
washout curve. In obstruction there is delayed or no washout. In dilatation without obstruction there is
good washout with furosemide.
Intravenous urography (IVU)
For renal structure, and function. Cannot be used in severe renal failure as dye is not excreted and is of
limited usefulness in the neonate as excretion is poor.
Normal kidney length on IVU is 3.5 to 4 vertebral bodies and the sizes of each do not differ by more than
1.5 cm
Retrograde and antegrade pyelography to evaluate the non functional and possibly obstructed kidney
Renal angiography detect malformations of renal vessels, measure renal vein and vena caval renin in the
evaluation of hypertension
Histology renal biopsy for histological evaluation of renal parenchymal disease.

15

BLOOD INVESTIGATIONS
Urea, creatinine, electrolytes, bicarbonate, calcium, phosphate, serum proteins, alkaline phosphatase, uric acid.
Hb. Blood urea is less accurate than creatinine for assessing renal function as it may be increased by many non
renal factors e.g gastrointestinal bleeding, steroids, high protein diets, an reduced in prolonged malnutrition.
Normal values vary with age, sex and size. At birth the urea and creatinine reflect maternal values, but fall to
the paediatric range by 2 weeks.
NORMAL VALUES
Acid -Base status (Blood Gases)
PH
Newborn
1 day
2 days adult

Arterial
7.33- 7.49
7.25- 7.43
7.35- 7.45

Venous
7.32- 7.42

PCO2

Birth 2 years
2 years adult

26 41mmHg
33 46mmHg

40 50mmHg

PO2
(room air)

Newborn
Child adult

65 76mmHg
80 100mmHg

25 47mmHg

Newborn
2 months 2 years
Child
Adult

Actual
Bicarbonate
17 24mmol/l
16 24mmol/l
18 25mmol/l
18 29mmol/l

Plasma Bicarbonate (not by blood gases)

Age

Plasma Bicarbonate (mmol/l)

Term neonate
Preterm neonate
Infants
Children

21 23
19 22
18 - 22
20 26

From Pediatric Nephrology (1987 edition) Holiday, Barratt, Vernier-Editors, Williams

and Wilkins Publishers ( pages 288, 927)
Phosphate (Phosphorus) (mmol/l)

Serum Calcium (mmol/l)

Age

Phosphate

Calcium (total)

Birth 1 mo
1 4 mo
4 mo 1 yr
1 4 yr
4 8 yr
9 14 yr
> 14 yr

1.62 - 3.10
1.55 2.62
1.30 2.20
1.16 - 2.10
1.16 1.81
1.07 1.71
0.87 1.53

Premature (birth 7 days)

Term (birth 7 days)
Child
Adult

1.75 2.5
1.8 3.0
2.25 2.74
2.12 2.62

Calcium (ionized, free) (mmol/l)

> 1 month adult

1.0 1.35

16

Correction of serum calcium for hypoalbuminaemia: (2 methods)

For every 10 g/l serum albumin is below normal (40g/l), serum calcium rises by 0.2 mmol/l
e.g. serum alb = 20g/l, measured serum Ca = 2 mmol/l , true serum Ca = 2.4 mmol/l or

True serum calcium mmol/l = [measured serum calcium (mmol/l) - serum albumin (g/l) ] + 1
[
40
]

Alkaline phosphatase produced by bone, liver, kidney, intestinal mucosa

Male Age
Alkaline phosphatase (IU/l )
Female Age
(years)
Males
Females
(years)
_____________________________________________________________________
<1
175 600
185 555
<1
18
175 400
185 520
12
9 11
180 - 475
185 425
38
12 15
200 630
160 500
9 13
16 17
100 455
90 - 400
14 15
18 19
80 210
45 140
16 18
> 19
60 150
25 100
> 18

Potassium (mmol/l or mEq/l)

Premature infants
Term infants
2 days 2 weeks
2 weeks 3 months
3 months 1 year
1 16 years

Sodium (mmol/l or mEq/l)

4.5 6.5
5.0 6.5
4.0 6.4
4.0 6.2
3.7 - 5.6
3.5 5.2

Premature infant
Term infant
Child
Adult

Correction of serum sodium for hyperglycaemia:

True serum Na (mmol/l) = measured Na (mmol/l ) + blood glucose (mmol/l )
5.5

132 - 140
133 - 142
135 - 143
135 - 145

X 1.5

Creatinine (mol/l). Serum creatinine is reduced in malnourished or small children. In general, the normal
serum creatinine (mol/l) is < [age (yrs) x 10], eg normal Creatinine for a 9 yo is < 90mol/l)
Age (yr)
<5
56
67
78
89
9 10
> 10
adult male
adult female

Creatinine
< 44
< 53
< 62
< 71
< 80
< 88
< 106
<122
< 101

Urea (mmol/l)
Age
Newborn
1 2 years
2 16 years

Urea .
2.9 - 10
1.8 5.4
2.9 7.1

Uric acid (mmol/l)

Any age
0.2 0.47

17

Figure 2 Body surface area nomogram for

children and adults (From Haycock GB,
Schwartz, Wisotsky DH. J Pediatr 1978; 62 66)

Figure 3 Body surface area nomogram for infants

(From Haycock GB, Schwartz GJ, Wisotsky DH. J
Pediatr, 1978; 93: 62 66)

References:
1. Pediatr Clin N Am 1997, 44:1065 1089 Imaging in pediatric urology
2. Am J of Roentgenology 1986, 145: 611 616 Sonography of kidneys in children
3. Pediatr Nephrol TTKG ref (journal)
4. J Pediatr (1990) 116: 243-247 for spot urine prot/creat reference
5. Urolog Clin N Am 1995, 22: 205 219, 1 - 20
6. Pediatric Nephrology, 2nd Edition (1987). Holiday , Barratt, Vernier- editors, Williams and Wilkins
publishers -926 928, 282 299
7. Residents Handbook of Pediatrics 7th Edition (1987). Abelson and Smith - Hospital for Sick Children735 - 797
8. Pediatric Nephrology, 4th Edition,(1999) Barratt, Avner and Hammond-Editors. Clinical methods:
Chapters 18-22, pages 317-390
9. Ped Clin N Am 1987, 34: 571 589, Use of plasma creatinine for estimating glomerular filtration rate in
infants, children, adolescents Schwartz et al
10. Manual of Nephrology Diagnosis and Therapy 3rd Edition, 1980. Shrier RW.
11. Contemporary issues in nephrology Vol 25, 1992 Diagnostic techniques in renal disease (305 330)
12. TTKG reference Pediatr Nephrol (1990) 4: 105 -110

18

CHAPTER 2
RED URINE and HAEMATURIA
Haematuria
Definition:
>5 rbc/ hpf on microscopy of the sediment of a freshly voided urine centrifuged at 1500 3000 rpm for 5
minutes
The diagnosis can only be made by urine microscopy
Not all red or dark urine is true haematuria
Evaluation of patient with red urine
Test with Hemastix/ Labstix
+ blood
centrifuged microscopy

< 5 rbc /hpf

Myoglobinuria

numerous rbc
true haematuria

OR

OR

Haemoglobiuria

no blood
pigments
External- drugs, dilantin, pyridium, rifampin,
senna, beets
Internal pink diaper syndrome (urates)
red diaper syndrome (Serratia)
bilirubin (yellow-brown)
porphyrins (red)
alkaptonuria (black)

external contamination
of urine with blood

Centrifuge patients blood

Clear serum

pink serum

Myoglobinuria

haemoglobinuria
(haemolysis)

Idiopathic

Drugs quinine, sulphonamides

Chemicals carbon monoxide
Fava beans, chloroform
Exercise, cold, intravascular haemolysis
Traumatic

19

TRUE HAEMATURIA
Microscopy
RBC, WBC, bacteria

UTI likely

RBC
Crenated

Not crenated

Glomerular

Non-glomerular

Proteinuria

absent

> 2+ with gross haematuria

> 1+ with micro haematuria

non glomerular

present
glomerular
(rbc casts, smokey urine, painless)

usually painful
bright red

Renal/bladder ultrasound
Abnormal - tumour, obstruction, calculus, clots
Normal - usually non surgical haematuria
Renal function
Abnormal >>>> renal biopsy >>> glomerulonephritis (GN)
Normal >>> check family history
Family history of haematuria/renal disease
>>> present >>> possible renal biopsy (GN)
>>> absent >> exclude hypercalciuria / coagulopathy

Pattern of haematuria
? renal biopsy for GN
Persistent >>>>
Recurrent >>>>
? IgA nephropathy (gross haematuria coincidental with URI)

>>>> observe

Adapted from Pediatric Nephrology 4th Edition 1999, pg 317 318 Editors Barratt, Avner and Harmon

20

Haematuria: aetiology
:
Renal:
trauma, stones, Bergers ( IgA nephropathy), benign essential haematuria
sickle haemoglobinopathy AS, SS, Sthal, - acute papillary necrosis
cysts, tumour
haemangioma, AV malformation
Non- renal (usually painful)
Trauma to genitourinary system
Stones, hypercalciuria, UTI, hyperuricosuria
Lesions of external genitalia
Contamination of urine with menstrual or rectal blood
Systemic disease: Coagulopathy haemophilia V111, 1X, drugs heparin, coumadin, Vit K deficiency;
thrombocytopoenia ITP, drugs eg cyclophosphamide
3 tube test (Gross haematuria)
Initial haematuria (first tube) distal urethra, urethritis, meatal stenosis
Terminal haematuria (third tube) posterior, bladder neck or trigone
History
Symptoms of UTI, glomerulonephritis, trauma, stones. Past history of haematuria, bleeding diathesis,
sickle cell disease /trait. Preceding URI or skin sepsis. Family history of renal disease, haematuria or
deafness or sickle cell disease / trait.
Examination
Growth parameters, BP, temperature, abdomen for masses, trauma, obstructive uropathy, pyelonephritis,
genital area for trauma. Document oedema, skin or throat infection. Actually inspect the diaper for
blood salmon coloured powder which can be scraped from the diaper is amorphous urates. Ask parent
to actually describe the colour and consistency of the material they are calling blood.
Aetiology
In UHWI paediatric population usually acute glomerulonephritis, followed by urinary tract infection
/cystitis, hypercalciuria, trauma , sickle haemoglobinopathy and suspected Ig A nephropathy.
The etiology of haematuria may be determined by the results of urine microscopy and urine tests for
protein. see algorithms.
Investigations
Investigations depend on likely cause.
General :
Urine microscopy, urine culture, urine test for protein
Hb electrophoresis
Coagulation profile PT, PTT, platelet count for gross haematuria
Spot urine calcium: creatinine for hypercalciuria
Mid stream urine for culture and sensitivity
Renal causes:
Blood urea, creatinine and electrolytes, serum albumin, spot urine protein/creatinine if proteinuria
Serum calcium, phosphate, uric acid and alkaline phosphatase if stones suspected
Renal ultrasound obstruction, cysts. CT scan or IVP for trauma
Test urine of first degree relatives for blood
Renal causes continued:

21

Serology ASTO, C3, ANF, VDRL, hepatitis B surface antigen suspected AGN
Immunoglobulins elevated IgA in some patients with IgA nephropathy / Bergers disease
In recurrent gross haematuria, renal biopsy is considered if:
Non glomerular haematuria excluded
Strong family history of nephritis
Recurrent gross haematuria and persistent microhaematuria for > 1 year
Nephrotic syndrome coexistent
Systemic illness
Undiagnosed or progressive glomerulonephritis
Families need for specific diagnosis
Non renal causes
Investigation depends on suspected cause. Urological referral may be necessary. Refer patients to urology
if haematuria heavy with clots.
Treatment and prognosis depend on the cause.
Familial benign essential haematuria FBEH

Familial occurrence of microscopic haematuria

Without proteinuria
Without progression to renal failure
Without hearing defect or other extra renal manifestations
EM diffuse attenuation of glomerular basement membrane (GBM) thin basement membrane disease
is not a specific diagnosis nor is it specific for FBEH.
Autosomal dominant
May be indistinguishable from heterozygotes of autosomal recessive Alports syndrome

IgA nephropathy
Recurrent gross haematuria usually occurring 1 2 days after a respiratory tract infection eg sinusitis
or tonsillitis.
Prognosis variable
Haematuria in the neonate - gross haematuria is rare
Bleeding tendencies Vit K deficiency
Trauma external meatus, urethra, bladder, post bladder tap, bladder haemangioma
UTI
Obstructive / reflux uropathy
Nephritis interstitial nephritis drugs eg aminoglycosides / glomerulonephritis
Vascular disorders ATN, corticomedullary necrosis, renal vein thrombosis, adrenal hemorrhage
Cystic disorders ARPKD (autosomal recessive polycystic kidney disease), MCDK (medullary cystic
disease of the kidneys, cystic dysplasia
Tumours Wilms, mesoblastic nephroma, fetal hamartoma, angioma
References;
1. Pediatric Nephrology (1999) 4th Edition. Barratt, Avner and Harmon Editors: 317-318, 698,700-701,
1053-1054,497 498
2. Ped Clin N Am (1997) 44:1191 1210 Hematuria
3. A practical primary care approach to haematuria in children. Ped Neph (2000) 14: 65-72

22

CHAPTER 3
PROTEINURIA
Definition:
Presence of protein in the urine.
Classification: (temporal)
Persistent
Transient
Intermittent - orthostatic
Classification: (etiological)
Pre glomerular - (overflow) excessive protein production exceeding renal tubular absorptive capacity
e.g. Bence Jones proteinuria
Glomerular - defect in glomerular filtration barrier - glomerulonephritis, microalbuminuria as early
index of glomerular disease in diabetes mellitus
Post glomerular (tubular) failure of absorption of normal filtered low molecular weight proteins
e.g. lysozyme, B2 microglobulin reflects tubular damage
Normal proteinuria
70% - globulins from the kidney, urinary tract, seminal glands. 30% - albumin.
Tamm Horsfall glycoprotein is formed in the kidney and is the main constituent of matrix of urinary casts
Trace/negative proteinuria
Spot urine protein(mg/dl)/creatinine (mg/dl) < 0.2
24 hour urine protein < 150 mg/day
<4mg/m2/hr in 12 24 hour urine collection
MEASUREMENT OF URINARY PROTEIN
QUALITATIVE:
Urine dipstick (albustix) tetrabromophenol blue buffered to alkaline pH to a yellow colour in the
absence of protein. Varying degrees of proteinuria produce increasing shades of green (dark green =
4+ proteinuria).
False positive: concentrated and alkaline urine- pH>8, contamination with chlorhexidine or
benzalkonium
False negative in dilute urine

3% Sulphosalicylic acid (SSA) -

Add 0.5cc of 3% SSA to 0.5cc urine in a test tube. The resultant turbidity reflects the degree of proteinuria
(see below).
False positives - concentrated urine, penicillin, Gantrisin, p Aminosalicylic acid, radiographic contrast
agents, suphonamides, tolbutamine, cephalosporins.
False negative in dilute urine

23

Urine testing with SSA (3%) vs Albustix

Urine protein concentration
(g/l)
<5
5-10
10-30
30 -100
100-500
>500

Reaction
(place print behind test tube)
clear
faint turbidity can read print
turbid can see black lines
white cloud cant see black lines
white cloud with precipitate
Flocculent precipitate -gel

Albustix
negative
trace
1+
2+
3+
4+

SEMIQUANTITATIVE
Spot urine protein (mg/dl)
.
Spot urine creatinine (mol/l) X .0113 (= mg/dl)
Normal < 0.2
Minimal proteinuria 0.2 0.5
Moderate proteinuria 0.5 2.0
Nephrotic proteinuria >2
QUANTITATIVE
Timed urine 12 24 hour urine collection
SIGNIFICANT PROTEINURIA
1+ on 2 of 3 random urines if urine S.G. < 1.015
> 2+ if urine S.G. >1.015
Urine protein/creatinine ratio > 0.2 (on early morning urine)
4 39 mg/m2/hr in 12 24 hour collection
nephrotic range proteinuria
> 40mg/m2/hr in 12 24 hr collection
.05g/kg/day in 24 hr collection
urine protein/creatinine >2.0
Significant proteinuria related to age
AGE
2 12 months
3 4 years
4 10 years
10 16 years

SIGNIFICANT PROTEINURIA mg/day

(>2SD above mean)
>155
>140
>190
> 250

Based on weight at 50th percentile for median age category

EVALUATION OF PROTEINURIA
Ideal sample for testing:
first voided morning urine sample (rule out orthostatic proteinuria)
after cleaning genitalia (rule out contamination with genital mucous)
PROTEINURIA ALONE IS USUALLY BENIGN
PROTEINURIA WITH HEMATURIA IS ALWAYS PATHOLOGICAL

24

IF RANDOM URINE DIPSTIX PROTEIN > 1+

Test sample with SSA a) < 1+ protein /pH >6
b)

> 1+protein / pH < 6

=
=

false positive on dipstix

no further investigation or treatment
positive SSA test for protein
= contamination OR true proteinuria

Positive SSA test

Clean genitalia and collect MSU
a) No proteinuria = false positive = contamination
b) Proteinuria
Proteinuria despite cleaning
a) Culture MSU, urine microscopy (uncentrifuged)
Positive culture / bacteria, WBC on unspun urine
+/- Blood on dipstix
urinary tract infection
b) Repeat test for protein x 2 (total of 3 samples)
c) Test urine for blood (dipstix and centrifuged urine microscopy)
Proteinuria in 1of 3 samples - transient proteinuria- exercise, fever, dehydration
No further investigation
Proteinuria in > 2 samples
a) Proteinuria and haematuria = glomerular / tubulo-interstitial disease >>>>>> investigate
b) Isolated proteinuria (without haematuria)
>>>>> Perform orthostatic test
a) Positive orthostatic proteinuria
b) Negative benign persistent proteinuria,
some glomerular and tubulointerstitial diseases,
reflux nephropathy, renal hypoplasia,
nephrotic syndrome.
HISTORY preceding streptococcal infection, SLE, UTI, oedema, gross haematuria, failure to thrive,
drug ingestion, oliguria, urethral or vaginal discharge. Family history of nephritis, renal failure.
EXAMINATION- growth parameters, BP, oedema, renal masses, obstructive uropathy, signs of collagen
vascular disease, skin or throat sepsis, genital discharge.
LABORATORY INVESTIGATION OF PERSISTENT PROTEINURIA
General:
Qualitative orthostatic test void at bedtime. Collect first void in the morning and last void at night for
3 consecutive days and label a.m. and p.m.. Freeze and test (on return to clinic) for protein.
Trace/ negative proteinuria on recumbent (a.m.) urines and > 1+ on ambulant (p.m.) urines
= orthostatic proteinuria.
Urine microscopy centrifuged and uncentrifuged, MSU for culture.
Urea, creatinine, electrolytes, albumin and total proteins (blood).

25

Spot urine for protein /creatinine (+/- 24 hour urine protein and creatinine collection).
Hb and Hb electrophoresis.

Specific:
For orthostatic proteinuria
If < 12 years and proteinuria <1.0 gm/day - as for general investigations
Follow up yearly examinations and repeat of renal function tests and urine protein quantitation
If >12 years old and proteinuria > 1.0 g/day investigate as for non orthostatic proteinuria (see below)
For persistent non orthostatic proteinuria
ASTO, ANF, C3, VDRL, Hepatitis B surface antigen
Renal ultrasound (renal anatomy) +/- renal glucoheptonate renal scan for scarring
MCUG if reflux nephropathy or obstruction suspected
Renal biopsy may be indicated
INDICATIONS FOR RENAL BIOPSY IN PROTEINURIA
-Atypical nephrotic syndrome
-Failure to thrive, systemic illness
-Haematuria and proteinuria (suggesting nephritis)
-Renal failure
-Family history of chronic nephritis or renal failure
-Increasing proteinuria on follow-up.
If all tests normal and proteinuria is not nephrotic diagnosis is Benign Persistent Proteinuria.
Follow-up as for orthostatic proteinuria
Prognosis:
Benign persistent proteinuria excellent
Orthostatic proteinuria 85 90 % of adults lose their proteinuria over 10 years of observation.
References:
1. Urinary protein excretion in healthy children. Mitenyi M. Clinical Nephrology (1979) 12; 216-221
2. Pediatrics in Review (1984) 8: 248-254
3. An office approach to hematuria and proteinuria . Ped Clin N Am (1987) 34:345-552

26

CHAPTER 4
ACUTE GLOMERULONEPHRITIS (AGN)
Definition:
AGN is acute glomerular inflammation characterized by haematuria, proteinuria, hypertension, oliguria and
azotemia.
Aetiology:
In the local context, acute post infectious GN (most frequently post Streptococcal (PSGN)) is the most
common, followed by Hepatitis B, syphilis, typhoid, leptospirosis, HIV to name a few. Less frequent
causes include:
Multisystem disease eg auto-immune (Systemic Lupus Erythematosus -SLE, polyarteritis nodosa),
Henoch Schonlein Purpura, Haemolytic uraemic syndrome (HUS), Wegener's granulomatosus
Primary glomerular disease e.g. IgA nephropathy (Berger's disease), Good pasture's syndrome,
idiopathic membranoproliferative GN
Drugs e.g. penicillamine
History:
Sore throat, skin sores, arthralgia, arthritis, skin rash, (petechial, prupuric or malar) , systemic symptoms,
preceding diarrhoea (bloody or otherwise) seizures (HUS). Urine: colour and volume; headaches, vomiting.
Previous treatment, family history of nephritis, deafness, haematuria.
Examination:
Height, weight, body surface area (m2) , oedema, skin rash, joint involvement, BP, cardiac failure,
hypertensive encephalopathy, fundoscopy.
Investigations:
Spot urine- microscopy of sediment of fresh centrifuged urine for rbc, WBC, casts (record as # seen/ high power
field)
dipstix for blood, protein, pH
to Chem. Path for protein and creatinine (calculate urine protein/creatinine to quantitate proteinuria
Microbiology- skin and throat swabs if indicated; stool cultures especially in suspected HUS
Blood Hb, Hb electrophoresis, WBC and film (ESR unhelpful), platelet count, PT, PTT, (if gross haematuria
or if HUS suspected,)
also add Fibrinogen and fibrin split products if HUS suspected
blood urea, creatinine, electrolytes and bicarbonate, serum calcium, phosphate and albumin (note
calcium correction for hypoalbuminemia see Chapter 1) (In PSGN blood urea/creatinine ratio is
elevated and cannot be used to determine if renal failure is intrinsic renal or pre-renal.) Estimate GFR
using Schwartz formula using Ht and serum creatinine (Chapter 1)
Serology: C3 (in all patients)
- ASTO, C3 - if history and examination suggest PSGN. ASTO should be repeated in 2
weeks.
- add ANF, VDRL, Hepatitis B surface antigen, Immunoglobulins if cause of nephritis
uncertain from clinical features
- add HIV if features suggestive, and HTV-1 if infective dermatitis
- (WIDAL - if indicated ). Leptospira agglutination tests (to Government Veterinary
Lab)
Early renal biopsy if cause of AGN appears not to be Post Streptococcal- eg SLE, Hepatitis B, or if
renal failure severe or persistent (Nephrology consult)
Late renal biopsy - failure of suspected PSGN to resolve as expected
Haematuria should be diagnosed by urine microscopy (>5rbc/hpf), and not by Labstix or the colour of the
urine

27

Importance of Complement measurement

C3 is diagnostically helpful as it is usually reduced in acute PSGN, membranoproliferative GN (MPGN),
SLE, typhoid, syphilitic and shunt nephritis, cyroglobulinaemia, bacterial endocarditis, some cases of HUS,
but is normal in most other glomerular diseases.
Treatment
1. Admission criteria: oedema, renal impairment, hyperkalemia, oliguria, hypertension, poor likelihood of
out-patient follow-up.
2. Bed rest necessary only if uncontrolled hypertension, or clinically ill
3. Penadur in therapeutic doses for Streptococcal infection (Remember dose adjustment if renal failure)
4. Diet: low sodium - 2mEq/kg/day if normotensive, 1mEq/kg/day if hypertensive; low K (1.00.5mEq/kg/day), low protein 1g/kg/day (or less if uraemic), low phosphate if in renal failure. Maintain
dietary restrictions until oliguria, oedema, hypertension and azotaemia resolve.
5. Fluids; 75% of maintenance for the first 24 hours then 400ml/m2/day (insensible) + previous day's
urine output. More severe fluid overload may require stricter fluid restriction initially. If congestive
cardiac failure - fluids at 400ms/m2 only and consider dialysis (Digoxin ineffective in cardiac failure
due to fluid overload) (See also Capter 6)
6. Hyperkalemia:
(K+) 5-6mEq/l- dietary restriction and Furosemide
(K+) 6-6.5 NaHCO3 and Resonium A (Kayexalate ) - sodium sulfonic polystyrene
(K+) > 6.5 NaHCO3, glucose and insulin, dialysis
7. Blood pressure (BP) every 4 hours
8. Accurate intake and output, daily weight
9. Urinalysis daily - first morning urine, urine microscopy of centrifuged urine at least once per week and
on discharge
10. Blood urea, creatinine, bicarbonate, electrolytes (U+E's) daily until oliguria ceases, renal function is
stable and electrolyte imbalance has resolved, the at least weekly.
The results of U+E's in all renal patients must be reviewed the same day that the sample is collected
11. Note indications for peritoneal dialysis (Chapter 11)
12. For hypertension: (see also Chapter 13)
If intermittent and mild - Hydrallazine 0.2mg/kg IM q4h prn for diastolics > 95th % for age
and height
- Furosemide IV /po (1mg/kg if normal renal function; 2mg/kg (or more) if renal failure)
may be added
- Mild/moderate - Furosemide, Hydrallazine +/- B blocker (if not asthmatic or in heart
failure), Ca channel blocker eg Nifedipine, ACE inhibitor eg. Captopril
- Severe - (see Hypertensive crises) - Furosemide IV / Diazoxide IV / sublingual Nifedipine
/ Minoxidil po, or titrated IV Hydrallazine, Na nitroprusside IV infusion
13. IV Furosemide 1-2 mg/kg/day as as single dose (maximum single dose 10mg/kg) - on admission if
oliguria is marked
14. Discharge when oedema has resolved, hypertension has resolved or is controlled, and azotaemia is
resolving.
15. Treat underlying cause of AGN if evident (eg SLE)
Follow-up of AGN:
If uncomplicated PSGN with normal couse of resolution, follow for at least 2 years or until urinary
abnormalities resolve. (Local data on PSGN in childhood is awaiting analysis). Longer-term follow-up
would be required for: nephrotic proteinuria or nephrotic syndrome, severe renal failure, atypical course for
PSGN (see below)
On each visit - BP, height, weight, and urinalysis for blood and protein, centrifuged urine microscopy if
possible. Always check that results are normal and refer to POPD renal if they are not.
At 6 weeks post AGN in addition: repeat C3 (should be normal), Hb, urea, creatinine, electrolytes,
bicarbonate, albumin, spot urine protein/creatinine to quantitate proteinuria, estimate GFR (Schwartz
formula Chapter 1)
At 6 months post and 1 year post AGN and yearly thereafter - investigate as for 6 weeks post but omit C3.

28

NORMAL COURSE IN ACUTE PSGN

ABNORMALITY

MAXIMUM DURATION

Oliguria
Gross haematuria
Azotaemia
Hypertension
Hypocomplementemia
Haematuria with proteinuria
Isolated microhaematuria or isolated proteinuria (low grade)

2 weeks
4 weeks
4 weeks
4 weeks
6 weeks
6 months
years

Consider renal biopsy / nephrology consultation in patients with suspected acute PSGN who:
1. Fail to respond as above
2. Have nephrotic syndrome
3. Have severe renal failure (estimated GFR < 50% of normal for age)
4. Have rapidly progressive course
5.
RENAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS
Though it is somewhat controversial, some authors recommend, that all children with SLE should have a
renal biopsy as renal pathology may be present even in the absence of clinical renal involvement. Repeat
biopsy may be needed if the clinical presentation changes, or to monitor response to therapy
Histological classification:
Class 1 - normal histology - asymptomatic - no treatment required
Class II - mesangial proliferation- mild proteinuria and microscopic haematuria, usually normal glomerular
function- no specific treatment- careful follow-up as progression is possible
Class III - focal segmental GN
< 20% glomeruli involved - < 5% risk of progression to renal failure within 5 years
> 40% glomeruli involved - more severe - active urine sediment, nephrotic syndrome,
hypertension, +/- moderate renal insufficiency - similar to DPGN (Class IV GN) -same
treatment as Class IV
Class IV - diffuse proliferative GN - severe - haematuria with casts, nephrotic syndrome, hypertension,
moderate to severe renal insufficiency -high risk for end stage renal disease if not treated aggressively
- IV pulse methyl prednisolone 30mg/kg (maximum I gm) daily for 3 doses, followed by IV
Cyclophosphamide monthly for 6 months with daily oral prednisone weaned over several
months. (Nephrology consultation required)
Class V -pure membranous - mild proteinuria, normal renal function,- good prognosis- 5 year survival 85%
- no specific treatment - (?treatment if nephrotic)
-membranous with proliferation - moderate proteinuria +/- haematuria +/- nephrotic syndrome,
moderate renal faiure, hypertension - treatment with IV pulse methyl prednisolone / Chlorambucil / and
oral steroids (Nephrology consultation required)
Class VI - chronic sclerosing GN - end stage renal failure - unlikely to be responsive to treatment
HAEMOLYTIC URAEMIC SYNDROME (HUS)
Definition:
Triad of acute renal failure, microangiopathic haemolytic anaemia (fragmented rbc) and thrombocytopenia.
Thrombocytopenia is not invariable and thrombocytosis may be noted if diagnosis is made late. In North
America, most cases are of classical HUS with the prodrome of bloody diarrhoea (D+ HUS), and are
associated with verotoxin producing E coli (Stx HUS) - Shiga toxin associated HUS). In HUS, diarrhoea
may not be bloody and may even be absent, and it may follow a respiratory prodrome. HUS may occur
with UTI secondary to Stx producing E coli 0103:H2, and with other infections such as Strep pneumonia,

29

Typhoid fever, gram negative septicemia, HIV and HTLV-1. In Jamaica, our cases appear to be triggered
by systemic infections, have severe CNS involvement and guarded outcome, but data are preliminary and
our cases are few. Thrombotic thrombocytopenic purpura (TTP) - another form of thrombotic
microangiopathy (TMA) is similar to HUS, but differs primarily in that it is mainly a disease of adults, and
whereas HUS affects the kidneys predominantly, TTP tends to have more multisystem involvement. The
distinctions are not always clear-cut. Differentials include Viral Haemorrhagic Fevers, Leptospirosis and
DIC.
History:
HUS should be suspected when a patient with diarrhoea develops progressive oliguria despite
correction of dehydration, sudden pallor, mild jaundice (secondary to haemolysis) and petechiae (from
thrombocytopenia).
Diarrhoea (type), haematuria, oedema, cough, myalgia, fever, jaundice, abdominal pain, vomiting,
oliguria, anuria, conjunctivitis, seizures, decreased conscious level, bleeding. Enquire about water
source? boiled, milk source ? pasteurized, presence of mosquitoes (Dengue) and rats ( Leptospirosis) ,
other affected individuals
Past history - previous illnesses, renal disease, sickle cell disease, seizures and drugs. Family history
of renal disease
Examination:
as for acute glomerulonephritis. Note jaundice and eye signs (corneal cloudingobserved in our cases)
Investigations at UHWI
1.

Haematology:
Hb electrophoresis, Hb, WBC, differential, platelet count, reticulocyte count and film - for
fragmented and burr cells and reticulocytosis
PT, PTT ,G6PD screen, fibrinogen and fibrin degradation products (special tubes from
Haematology)
Repeat haematology including film daily or alternate days ,and coagulation screen as indicated
Direct Coomb's test, cross match and reserve 10cc/kg packed cells and 20cc/kg FFP if bleeding or
ill looking
Haematology consult
2. Chem Path:
blood urea, creatinine, electrolytes, bicarbonate, albumin, calcium, phosphate ,alkaline
phosphatase, SGOT.,GGT, LDH, HBD, glucose, amylase (watch for hepatitis and pancreatitis)
spot urine - protein, creatinine, phosphate ( calculate degree of proteinuria and tubular
reabsorption of phosphate), Na, K
urine microscopy (centrifuged)
Estimate GFR using Schwartz formula

daily urinalysis for protein and blood

3.

Serology / virology / microbiology;

C3, ANF, VDRL (+ Hepatitis B surface antigen if jaundiced
Leptospira agglutination test - (clotted sample sent to Government Veterinary Laboratory by
ambulance, WIDAL and clot culture ( if diarrhoeal prodrome), Immunoglobulins, HIV ( if infections
severe)
Acute and convalescent serum - 10 days apart (7.5 -5cc) to Virology, labeled Haemolytic Uraemic
Syndrome. Give details of symptoms on the form
Stool (no preservative) or rectal swab for viral culture
Stool - culture and sensitivity (C&S), and ova and parasites
Swabs of infected lesions for C&S, CSF ( if LP done) , MSU for viral and bacterial cultures, blood C&
S when indicated
ALL VIRAL SWAB CULTURES ARE TO BE SENT IN TRYPTOSE PHOSPHATE BROTHlabeled Haemolytic Uraemic Syndrome

30

NOTE:
For patients with CNS involvement - Cranial CT scan, EEG, Neurology consult
Nephrology consult- all cases, renal ultrasound (+/- Renal biopsy)
Ophthalmology consult within 2 hours if abnormal eye examination eg cloudy cornea
Investigate symptomatic contacts as per index case (1-3 above)
All deaths should have Post Mortem - (contact Nephropathologist) -special attention to kidneys , brain,
lungs, liver, pancreas, heart, GI tract and any skin lesions
Initial treatment protocol
1. Catheterize all anuric/oliguric patients to accurately ascertain urine output. Accurate intake and output
measurements
2. Correct volume depletion of present by boluses of saline or Hartmanns's 20cc/kg over 1-2 hours or less
depending on degree of dehydration. Repeat if necessary.
3. If oliguria /anuria / renal failure persist despite (2) try Furosemide 2-4mg/kg IV push.
4. If still oliguria despite (2) and (3) or if fluid overloaded, uraemic, hyperkalemic, acidotic,
hyponatremic, hypertensive - peritoneal dialysis is indicated.
5. IV-D10W with 2mEq NaHC03 /kg/day at 400ml/m2 fluid /24 hours -till acidosis corrected. Increase
volume of D10 IV or p.o fluids when dialysis started and fluid overload corrected. Replace all losses stool, nasogastric drainage q4 h and urine q 1-4 hourly depending on volume
6. If phosphate elevated- treat with phosphate binders
Preferably Calcium carbonate 20-220mg/kg/day (Tums ) 1 tab = 500mg Ca CO3 in 1-3 divided
doses (with meals if eating)
or Aludrox 5-10 mls q 12 -6 hourly (less ideal)
7. If symptomatically hypocalcemic (serum calcium <1.9mmol/l) despite correction for
hypoalbuminaemia, start calcium infusion of 10% calcium gluconate: 0.2mEq/kg/hr of Ca2+. Repeat
serum calcium q4 h during infusion and adjust rate q4 h to keep serum Calcium 2.25mmol/l 2.75mmol/l. (Check serum phosphate daily, serum albumin alternate days). 1 cc of 10% calcium
gluconate -0.45mEq Ca2+ (See Chapter 7 for dilution of infusion)
8. GI bleed - ice cold saline lavage till clear - NGT on free drainage - aspirate q4 h and replace losses
with D10/ N saline. Calcium carbonate (or other antacid) 5-10 cc q2h via NGT - clamp 1/2 hour after
drug administered. - Dialysis will be required.
9. Seizures (hypertension, hypocalcemia, hyponatremia, uraemia, CNS infarct or bleed)
Abort seizure with conventional anticonvulsants
Treat acute hypertension (Hydrallazine titrated IV, IV push Diazoxide, sublingual Nifedipine, oral
Minoxidil or (in ICU) Na Nitroprusside) and then maintenance antihypertensives (see Chapter 13)
Correct metabolic disorder - Dialysis may be necessary
If seizures refractory to maximum doses of conventional anticonvulsants, may need to add
paraldehyde infusion -5.0 ml (1gm/ml) in 95cc of D5 0.2Ns at 0.5 -2cc/kg/.hr depending on
response
Neurology consult may be necessary
10. Packed cells 5cc/kg slowly e.g .(over 4 - 6 hours) if Hb < 6g/l and active haemolysis or bleeding. More
rapid infusion if shock or active bleeding. Risk of worsening hypertension and seizures during or after
transfusion if blood administered too quickly.
11. Platelets 0.2units /kg UV if platelet count <20,000/ml, or if active bleeding (Contact Haematology)
12. FFP if abnormal PT/PTT and bleeding. Plasma infusions are not recommended in D+HUS
13. In hypotensive, volume overloaded , oliguric patients:
CVP line (contact surgeons early)
IV dopamine 4-10g/kg/min in ICU adjusted to maintain normal BP
Dopamine dose dilution : (Dopamine dose (mg) for dilution = 6mg/kg )
diluted to 100cc with N saline - run at 1cc/hr = 1g/kg/min Dopamine
14. Watch for pancreatitis and hepatitis complicating HUS

31

Follow-up
1. Renal / liver : monitor blood urea, creatinine, electrolytes, albumin, bicarbonate, calcium, phosphate,
liver function tests every 3-6 months with Hb, WBC platelet count and reticulocytes. repeat C3 if
initially low. Urine: dipstix for blood and protein with microscopy for cells, Blood pressure and
growth parameters each visit.
2. Neurological- follow-up if CNS involvement, at least once to twice yearly in Neurology clinic. If
seizures were metabolic and no structural CNS damage present, anticonvulsants may be weaned off
before discharge once the underlying problem has been corrected.

References:
1. Acute glomerulonephritis - a clinical review. Medical Clinics of North America (1984) 68:259-279
2. Acute Glomerulonephritis -diagnosis and treatment: Pediatr Clin N America (1982) 29: 857 -873
3. Acute glomerulonephritis and crescentic glomerulonephritis Chapter 41. Pediatric Nephrology (1999)
4th Edition. Barratt, Avner and Harmon Eds. pages 669-689
4. Systemic lupus erythematosus Chapter 49 Pediatric Nephrology (1999) 4th Edition Barratt, Avner and
Harmon Eds -pages 793-810
5. Treatment of lupus nephritis in children - Pediatric Nephrology (2000) 14: 158-166
6. Hemolytic uremic syndromes Chapter 50 Pediatric Nephrology (1999) 4th Edition Barratt, Avner and
Harmon Eds - pages 811-834

32

CHAPTER 5
NEPHROTIC SYNDROME (NS)
Definition:
1. Massive proteinuria

> 0.05mg/kg/day or

> 40mg/m2 /hr on a 12 -24 hour collection or ideally an overnight sample

random urine protein/creatinine > 2 (mg/mg)
overnight urine protein/creatinine > 1.8 (mg/kg) _ Clin Neph (1988) 30: 225-229
persistently > 3+ proteinuria on qualitative assay on early morning urine sample
2. Hypoalbuminaemia (< 25g/l)
3. Oedema
4. +/- hypercholesterolemia or hypertriglyceridemia
Aetiology:
Minimal change nephrotic syndrome is quoted in world literature as the commonest cause of childhood NS,
but our local data (1984 - 1996) suggest that mesangial proliferative GN may be as almost as common.
Primary nephrotic syndrome is more common than secondary. Secondary causes in our series include: post
infectious - post Streptococcal GN, Hepatitis B, syphilis, HIV and HTLV-1, auto-immune-SLE, Sickle
haemoglobinopathy, and Wilms tumour
Other definitions:
Relapse: Proteinuria > 2+ on dipstix or sulfosalicylic acid (SSA) for 5 consecutive days, or proteinuria >
2+ on any day with oedema (cloudy urine on SSA testing)
Remission: Trace/ negative proteinuria for 5 consecutive days (clear urine on SSA testing)
Frequent relapses: > 2 relapses within 6 months
Steroid resistance: failure to achieve remission after a 28-day course of daily Prednisone
History:
Sore throat, (preceding or current), gross haematuria, symptoms of collagen vascular disease, sickle
cell anaemia, skin lesions - eg infective dermatitis (HTLV-1), skin sores (PSGN), purpura (Henoch
Schonlein Purpura) or HUS or collagen vascular
Previous treatment and response
Family history of renal disease, sickle cell anaemia, maternal syphilis
Examination:
Growth parameters, BP, oedema, signs of secondary nephrotic syndrome

Investigations:
CBC, Hb electrophoresis, electrolytes, bicarbonate, urea, creatinine, serum albumin, calcium and
phosphate.
For every 10g/l that albumin is below normal, the true serum calcium is 0.2mmol/l higher than
the measured value
cholesterol and triglycerides not essential for diagnosis - if done should be a fasting sample . ESR is
unhelpful as it is invariably elevated regardless of the cause of nephrotic syndrome
Serology - ASTO, ANF, VDRL, C3, Hepatitis B surface antigen. TORCH in congenital nephrotic
syndrome. HTLV-1 antibody (if infective dermatitis), HIV antibody (if suggestive history and
examination)
Microbiology - swab skin and throat if lesions present, ascitic fluid tap for gram stain and culture if
peritonitis suspected. Other bacterial cultures if indicated.
Urine tests:

33

dipstix for blood, protein and pH. Remember that alkaline UpH will give a false positive test for
protein using the dipstix. In such a case use the sulfosalicylic acid (SSA) test for urine protein.
(See Assessment of Renal Function)
spot urine for protein /creatinine (+/- 24 hour urine for protein and creatinine - 24 hour urine
quantitation is no longer absolutely necessary )
urine microscopy (centrifuged) for rbc, wbc and casts
+/- Renal biopsy

Indications for renal biopsy prior to steroid therapy: (i.e. features atypical for minimal change
nephrotic syndrome (MCNS)
1. age <1 year > 12 years (relative indication in the older child)
2. history suggestive of PSGN, auto-immune disease or other secondary nephropathy
3. persistent hypertension
4. gross haematuria (microhaematuria may occur in 20% of patients with MCNS)
5. renal failure not attributable to hypovolemia
6. positive serology, sickle haemoglobinopathy
7. hypocomplementemia is absent in MCNS and is seen in membranoproliferative GN (MPGN),
crescentic nephritis, PSGN, SLE, Hepatitis B infection, shunt nephritis, infective endocarditis and
some other post infectious causes
8. anaemia Hb<10g/l (when not due to nutritional deficiency) suggests MPGN (Membranoproliferative
GN), sickle Hbinopathy ,chronic renal failure
CLINICAL DIFFERENTIATION OF COMMON TYPES OF CHILDHOOD NS - by features at
initial presentation
HISTOLOGICAL
GROUP

MCNS
FSGS*
Mes prolif GN**

MEMBRANOUS
GN

MPGN
CRESCENTIC
PSGN (DPGN)

CONGENITAL
NS

PRESENTATION

Benign

benign but older

fulminant

Age
Hypertension
Gross haematuria
Renal failure
Anaemia
Positive serology

1-6 years
-

usually > 6 years

+/-

any age
+
+
+
+
+

usually signs of
underlying disease
eg syphilis
0-12 months
+/+/+ usually VDRL

Reduced C3

+/-

+/-

*FSGS (focal segmental glomerulosclerosis) -more likely to be hypertensive at onset - **Mes prolif GN
(mesangial proliferative glomerulonephritis)- more likely to have microscopic haematuria and mild
hypertension at onset. MPGN (membranoproliferative glomerulonephritis)- PSGN (post streptococcal
glomerulonephritis) DPGN (diffuse proliferative GN- usually post infectious)
Treatment: SPECIFIC
Treatment with Prednisone at presentation is indicated only in those children with clinical features
suggestive of MCNS.
All other children should be referred to a paediatric nephrologist for renal biopsy.
Standard MCNS protocol would under-treat MPGN, and crescentic GN, putting the patient at risk for
chronic renal failure, and give unnecessary treatment to spontaneously resolving post infectious
nephritides
Nephrotic syndrome secondary to other nephritides requires specific regimes and has variable
prognoses. Nephrology consult needed.

34

Treatment in MCNS, Mes prolif GN, FSGS:

To induce first remission: Prednisone 2 mg/kg/day (maximum 80 mg/day) - (alternatively 60mg/m2 /day)
in 3 divided doses for 28 days then
Maintain remission on first and subsequent relapses:
Prednisone 2mg/kg as a single dose on alternate mornings for 28 days then taper and discontinue over 2-3
months
To induce remission in subsequent relapses: Prednisone 2mg/kg/day (maximum 80mg/day) in divided
doses until remission occurs or for a maximum of 28 days
For steroid resistance, renal biopsy is needed. Renal biopsy is no longer indicated prior to further
therapy, for children who retain features of MCNS but have frequent relapses.
Frequent relapsing NS / steroid dependence / steroid resistant MCNS, FSGS, Mes prolif GN
1.
2.

Reduce Prednisone slowly and maintain on Prednisone / Prednisolone 0.1-0.5mg/kg alternate day for
up to 12 months
Relapse on Prednisone >0.5mg/kg alternate day and steroid side effects or relapse on Prednisone
>1mg/kg alternate day :
Cyclophosphamide 3 mg/kg/day as a single daily morning dose for 8 weeks, or 2-2.5mg/kg/day
for 12 weeks (maximum cumulative dose should not exceed 250mg/kg to avoid oligospermia.
Azospermia occurs at 500mg/kg). Prednisone at 2mg/kg/day as a single alternate day dose is given
during the full course of Cyclophosphamide then slowly tapered and discontinued.
liberal fluids and frequent bladder emptying to minimized risk of haemorrhagic cystitis
risk of sterility after prolonged courses of > 6 months
monitor CBC on alternate days for the first week then weekly for the first month, then every
2-3 weeks.
if WBC <5 x 109/l but >4 X 10 9 /l , reduce dose by 10%
if WBC <4 x 109/l, hold Cyclophosphamide and restart at 10% lower dose when WBC >5 x
109/l
Cyclophosphamide tablet is 50mg. If patient requires a lower dose the pharmacy makes up a
solution from the IV preparation to be given orally. It is an unstable preparation and has to be
re-made every 2 weeks, so patient will have to make 2 weekly visits to have prescription
refilled.
Discontinue Cyclophosphamide if : a) patient is exposed to or contracts rubeola or varicella b)
develops haemorrhagic cystitis
Side effects - haematological, haemorrhagic cystitis, transient mild alopecia, risk or sterility
and secondary malignancy
Clorambucil (if Cyclophosphamide unavailable) 0.1 -0.2 mg/kg /day as a single morning dose
for 8-12 weeks with a similar Prednisone regime as for Cyclophosphamide.
side effects - seizures, alopecia, haematuria and risk of infection, rashes . Cumulative dose
should not exceed 10mg/kg. Azospermia occurs at >18mg/kg cumulative dose.

Frequently relapsing / steroid dependent NS despite alkylating agents- used after remission induced by
Prednisone.
1. Levamisole (Ketrax) 2.5mg/kg as a single dose on alternate mornings for 4-12 months, with
Prednisone on alternate mornings as a single dose to be tapered slowly. Side effects - leukopenia,
allergic rashes,. Monitor CBC as for Cyclophosphamide and adjust dose similarly. Discontinue if rash
develops
2. Cyclosporin (expensive) -5.0 mg/kg/day (or 100-150mg/m2/day for 1 year with alternate day
prednisone tapered slowly. Need to monitor renal function and Cyclosporin levels. Risk of
nephrotoxicity.
Other treatment protocols for steroid resistant nephrotic syndrome - usually Steroid resistant FSGS
(Nephrology consult required)
Pulse methyl prednisolone (PMP)- short or long protocol (Nephrology consultation requried0

35

Several other modalities have been tried- including PMP with oral Prednisone and Cyclosporin/
plasma exchange and immunoadsorption / IV Vincristine pulses / IV pulse Cyclophosphamide with
oral prednisone

Nephrotic syndrome unresponsive to all therapeutic modalities - ACE inhibitors eg Captopril, Enalapril, for
protein sparing effect (S/E hyperkalemia, hyponatremia), diuretics for oedema control, Indomethacin
Enalalpril 0.2 - 0.8 mg/kg/day o.d. for prolonged periods (not for neonatal use)
Captopril 0.75mg/kg/ day (t.i.d) - increased by 1mg/kg each week if no response, to a maximum of
5mg/kg/day- maximum response in 6 weeks
Captopril/ Indomethacin 1mg/kg/day increased by 1mg/kg each week till response or maximun of
5mg/kg/day - risk of renal impairment
Vitamin E 200IU bid - said to reduce proteinuria in steroid resistant FSGS
Treatment - general
NB - In patients with nephrotic syndrome associated with renal failure and volume overload, the
management of the acute renal failure takes priority, and the patient is managed as for AGN with fluid
restriction.
DO NOT GIVE COLLOID TO PATIENTS (EVEN IF NEPHROTIC) IF THERE IS CLINICAL
INTRAVASCULAR VOLUME OVERLOAD
Treatment of patients with NS and presentation as per MCNS
1. Diet - Normal protein - 2mEq/kg/day while on daily steroids or oedematous
2. Fluids- maintenance for estimated dry weight. Fluid restriction in MCNS type nephrotic syndrome
will result in further intravascular volume depletion and pre-renal failure
3. Accurate intake and output and daily weight
4. Daily testing of first morning urine for protein (avoids detection of orthostatic proteinuria)
5. Culture and treat suspected systemic infection with antibiotics which cover both gram negative and
gram positive organisms eg Amoxil and an Aminoglycoside
Peritonitis is usually primary and due to Pneumococcus. A peritoneal tap will isolate the organism
. Finding several GNB on a peritoneal tap suggests a perforated viscus and a surgical abdomen. A
single gram positive organism is likely to be due to the NS and surgical consult is not needed as
this will resolve with medical treatment
Pneumonia is often pneumococcal
6. Oedema mild - no treatment required. Diuresis in 8-10 days of Prednisone if steroid sensitive
moderate - with normal renal function - Rx Spironolactone 3-5 mg/kg/day in 3 divided doses.
Increase from lower dose every 5 days if inadequate response. Monitor electrolytes for
hyponatremia and hyperkalemia. Combination with a thiazide Hydrochlorothiazide 1-2mg/kg
/day (od) or Bendrofluazide 0.1 - 0.2mg/kg/day (od) is often helpful
severe - see albumin and Furosemide
Furosemide should not be given without first giving colloid (albumin or plasma) in children with
MCNS type NS. Potent diuretics and severe fluid restriction may precipitate pre- renal failure.
Indications for colloid / and Furosemide
Nephrotic patients with anasarca, pre-renal failure, massive ascites or pleural effusions causing respiratory
distress, abdominal pain secondary to mesenteric ischaemia should ideally have 25% salt poor albumin
1g/kg IV over 2 - 4 hours followed by Furosemide 1 mg/kg IV after 2 hours of the infusion. If this is not
available, Fresh frozen plasma (FFP) (20cc/kg) over 4-6 hours with Furosemide 1mg/kg halfway through.
Watch for hypertension (treat with antihypertensives and reduce infusion rate) and cardiac failure (stop
infusion and give diuretic).
Follow-up
Patients should be educated about nephrotic syndrome and taught how to test the first morning urine
daily and record in a notebook. Labstix are expensive. 3% Sulfosalicylic acid (SSA) is available from

36

Chemical Pathology in stock bottles, which are kept on the ward. The bottles are to be kept filled and
'topped up before each renal clinic so patients may be supplied with the fluid. Usually 300cc is
adequate for about 2 months. Relapse and remission and the treatment of each, are explained. The
Prednisone dose for relapse is written in their book.The need for medical attention if relapse, fever or
exposure to measles or varicella occurs is emphasized.
NO LIVE VIRUS VACCINES SHOULD BE GIVEN TILL THE PATIENT HAS BEEN IN
REMISSION AND OFF PREDNISONE FOR AT LEAST 3 MONTHS
Patient instructions for 3% SSA test: patient is supplied with 2 plain tubes as well as SSA.
The first morning urine is tested.
A "finger joint" height of urine is poured into the test tube and an equal portion of SSA added.
If the liquid is clear like water or coconut water and print can be read through it - the test is
recorded as "CLEAR"
If the liquid is cloudy and print cannot be read through it - the test is recorded as "CLOUDY'
Relapse is "cloudy" urine for 5 days consecutively or any day with swelling (kidney is sick)- start
Prednisone in 3 divided doses and come to hospital to be checked
Remission is "clear" urine for 5 days consecutively (kidney is getting better) - take all the day's
Prednisone as a single dose on alternate mornings

Complications of chronic steroid resistant NS

Hypocalcemia - may need Vit D therapy
Hypothyroidism - may need Thyroid supplements
Anaemia - check for iron deficiency
Risk of infection - Penicillin prophylaxis (Pen V-daily or Penadur- monthly) to be considered for
children with a history of Pneumococcal sepsis with relapses. ? Role of Pneumococcal vaccine in our
population of childhood nephrotics
Hyperlipedemia - potential risk of accelerated atherosclerosis: treatment uncertain? Bile acid
sequestrants (Cholestyramine, Sitoserol) / Fibrates (Benzafibrate, Gemfibrozil). The safety of statins in
children has not been established.
risk of CRF
References:
1. Consensus statement on management and audit potential for steroid responsive nephrotic syndrome
Arch Dis Child (1994) 70: 151 -157
2. Steroid-responsive nephrotic syndrome Chapter 45, 731-747 Pediatric Nephrology 1999 4th Edition.
Barratt, Avner and Harmon Editors.
3. Steroid -resistant nephrotic syndrome Chapter 46, 749-777 Pediatric Nephrology 1999- 4th Edition .
Barratt, Avner and Harmon Editors
4. Management of the nephrotic syndrome in children. Pediatr Clin N America 23: 735-750
5. Nephrotic syndrome in childhood Pediatr Clin N America (1982) 29; 975-894
6. Should hyperlipidemia in children with nephrotic syndrome be treated? Pediatr Nephrol (1999) 13: 7784
7. Enalalpril and prednisone in children with nephrotic range proteinuria . Pediatr Nephrol (2000) 14:
1088-1091
8. For urine protein/creatinine ration: J Peds (1990) 116: 243-247
9. For treatment of hyperlipidemia : Pediatrics (1992) 89:495-501, 138-142, Suppl 525-584

37

CHAPTER 6
DISORDERS OF ELECTROLYTE AND WATER BALANCE
Sodium
Sodium is the major extracellular cation. Changes in sodium balance reflect changes in the volume of
extracellular fluid (ECF). Aberrations in water balance or ECF osmolality reflect changes in the balance
between total body sodium and total body water.
Sodium balance Factors controlling sodium loss
Aldosterone dependent.
Non aldosterone dependent
Na excretion increased by high GFR, high renal blood flow (RBF), haemodilution, atrial
natriuretic peptide (ANP), Dopamine, nitric oxide (NO), ADH, thyroxine, calcitonin,
glucagon, prostacyclin, oestrogen and progesterone.
Na excretion reduced by- very low GFR, low RBF, haemoconcentration, nor adrenaline,
prostaglandin inhibition.
Control of water balance
1. Thirst thirst centre in the hypothalamus responds to changes in plasma osomolality. Increases in
blood osmolality resulting in thirst and increased water intake
2. Increased Posm causes secretion of ADH (antidiuretic hormone) from the osmoreceptors in the
supraoptic and paraventricular nuclei of the hypothalamus. ADH acts? via aquaporins (water channels
in the collecting ducts) to increase the permeability of the distal renal tubular cells and increase water
reabsorption along an osmotic gradient resulting in a concentrated urine of high osmolality.
3. Non ADH dependent: When there is a high solute load in the glomerular filtrate, (eg glucose,
mannitol), the substrate is not fully reabsorbed from the PCT and loop of Henle resulting in the
inhibition of water and Na reabsorption in the PCT, a larger than normal volume in the DCT and
diuresis.
Maintenance requirements (Table 1)
Fluid (infants and children)

100ml/kg for first 10 kg body weight

50ml/kg for second 10kg
20ml/kg after 20kg

Neonate

120-150ml/kg/day by day 4

Premature neonate

May exceed 200ml/kg/day (higher in premature

neonates)

Sodium

2-3mEq/kg/day (higher in premature neonates)

Potassium

2-3mEq/kg/day

Ca 2+

2mEq/kg/day

Fluid requirements in fever:

For every oC rinse in temperature above 370C, fluid requirements increase by 10% of calculated
daily maintenance or
10 mls/kg/day
For every 0F rise in temperature above 99oF, water loss increases by 7mls/kg/day

38

DEHYDRATION
Dehydration reflects a reduction in total body water and may be classified by degree (mild, moderate,
severe) or in relation to serum sodium values (iso- hypo- and hypernatremic). The commonest cause of
dehydration is gastroenteritis. Mild to moderate dehydration may be corrected orally.
Assessment of Degree of Dehydration (Table 2)
% Wt loss
Fluid deficit
Degree
% Wt
Child
(ml/kg)
loss
Infant
Infant
Mild

5%

3%

50

Fluid
deficit
(ml/kg)
Child
30

Moderate

10%

6%

100

60

Severe

15%

9%

15

90

Clinical

Reduced secretions (tears, sweat, urine

output)
Reduced tissue turgor sunken
fontanelles and eyes, and reduced skin
turgor (abdomen), further oliguria and
tachycardia
Shock, reduced conscious level, fever,
severe oliguria

Types of Dehydration:
Isonatremic (isotonic) serum sodium normal
Hyponatremic (hypotonic ) Na <130mmol/l earlier ECF and plasma volume depletion
Hypernatremic (hypertonic) Na >150mmol/l plasma and ECF volume preserved longer
Etiology of Dehydration
May be secondary to decreased intake or increased losses from kidney, GI tract, lungs or skin. If USG is
>1.012 and U Na is <5mmol/l dehydration is non renal in aetiology.
If USG < 1.010 and UNa 10 20mmol/l, dehydration is caused by renal fluid loss e.g. diabetes insipidus.
History : Assess volume and type of intake and output, duration of losses, fever and treatment given.
Examination: Growth parameters, tempreature, BP, pulse, hydration status, level of awareness, associated
sepsis, acidotic breathing.
Investigations
General: Hb, WBC, differential, electrolytes, bicarbonate, urea, and creatinine. If dehydration is moderate
to severe, add calcium, glucose and albumin. Cross match for plasma if very severe. Spot urine for specific
gravity and urine Na.
Specific: Septic work-up if indicated, include urine cultures, stool cultures and parasitology where
indicated.
Treatment
1. Resuscitation: correct shock if present 20 cc/kg IV bolus as rapidly as possible using isotonic fluid
5% dextrose in normal saline, Hartmanns, fresh frozen plasma (FFP). FFP preferred if patient is
malnourished. Repeat bolus as often as is necessary to obtain satisfactory blood pressure and pulse
rate. Whole blood preferred if anaemic and in shock.
2. Add maintenance fluid (Table 10 to fluid deficit (Table 2)
3. Estimate ongoing losses
4. Subtract the volume used in resuscitation (1)from the maintenance +deficit volume (2)
5. In hypo or isonatremic dehydration
Give half of the remaining maintenance + deficit volume (2)-(1) over the first 8 hours and the
remainder over the next 16 hours
Estimate and replace ongoing losses q4h with fluid of appropriate concentration
Add KCl 10mEq/500ml of IV fluid once urine has been passed. May need more or less K
depending on renal function, serum K and ongoing losses.

39

Milder degrees of dehydration may be corrected orally using Oral Rehydration Fluid (ORF), but applying
the same principles for fluid management
6. If breathing is acidotic and serum bicarbonate unavailable, give Na bicarbonate 2mEq/kg IV: 1
mEq/kg diluted to 50% with water for injection and given over 15-30 minutes and the remainder in IV
fluids over the next 2-3 hours. Reassess acid base status when serum bicarbonate available (additional
bicarbonate may be necessary).
7. If serum bicarbonate <12mmol/l- determine bicarbonate deficit and supply in IV fluids over 2-3 hours.
Correct bicarbonate to about 15mmol/l
Bicarbonate deficit (mEq or mmol) = (Desired Initial Bicarbonate X 0 .6* X body wt (kg)
8.

Correction of hyponatremia
Na deficit (mEq) = (Na desired Na actual) x 0.6* x body wt. (kg)
*(in infants 0.75 should be used instead of 0.6)
Fluids given should provide sufficient sodium to
Replace deficit Na
Supply maintenance Na
Supply ongoing Na losses

9.

Profound symptomatic hyponatremia (Na < 120mEq/l) with seizures or coma requires rapid correction
to 130mEq/l with hypertonic saline (6% NaCl or if not available 8.4% NaHC03).
Serum Na should not rise by more than 10mEq/l/hour during correction to avoid CNS
demyelination.
6mEq/kg of NaCl /kg increases serum Na by 10mEq/l
Monitoring : careful monitoinr of response is crucial (BP, HR, hydration, urine output, losses,
weight, laboratory data) to determine adequacy of treatment. Fluid calculations are only guidelines
and must be adjusted according to patient response.

Sodium composition of various preparations (Table 3)

1gm salt
20mEq Na+
1gm sodium
40mEq Na+
4.3% dextrose in 0.18 N 31mEq Na+/l
saline
D5 / 0.45 N saline
77mEq Na+/l
D5 / N saline
154mEq Na+/l
6% Na Cl
1mEq Na+/ml
8.4% Na bicarbonate
1mEq Na+/ml
Approximate electrolyte composition of gastrointestinal fluids (mEq/l) (Table 4)
Gastric
Small intestinal
Pancreatic
Diarrhoea

H+
80
0
0
0

Na+
40
130
135
40-70

K+
20
20
15
40

Cl150
120
100
40

HCO3 0
30
50
40

Hyponatremia (serum sodium <130mmol/l)

Classification:
False / pseudo hyponatremia in hyperlipidemia, secondary to mannitol infusion and secondary to
hyperglycemia. For correction of serum Na for hyperglycemia see Assessment of Renal Function
Chapter 1. Hyperglycemia - associated hyponatremia will correct when hyperglycemia ceases and is
asymptomatic.

40

True hyponatremia

History: - gastroenteritis, polyuria, diuretics, excessive sweating, liver or renal disease, ambiguous
genitalia, hypothyroidism and drug ingestion. The severity of the symptoms (changes in sensorium)
depends on the rate at which the sodium has fallen. Signs and symptoms are more likely when the fall is
rapid and are most likely due to cellular swelling and cerebral oedema. Seizure and coma are most likely to
occur when serum Na falls below 120mmol/l. Elevation of serum Na to approximately 130mmol/l is
usually sufficient to correct the acute symptoms of hyponatremia. The treatment of hyponatremia depends
on the cause.
Examination hydration status, signs of endocrine, or renal disease. Blood pressure, oedema, cardiac
failure. Check growth parameters and nutritional status.
General investigations:
Electrolytes, bicarbonate, urea, creatinine, glucose, Hb.
Spot urine Na before any diuretic is given, urine specific gravity and osmolality, urine microscopy
of centrifuged urine (rbc and casts) and urinalysis for blood and protein
Evaluation of hyponatremia
Clinical examination

Hydration normal or slightly increased

Dehydration

No oedema

Renal losses

Extrarenal losses

Diuretic excess
Mineralocort
deficiency
Nephritis:
Salt wasting

gastroenteritis
excessive sweating

Oedema

SIADH
Hypothyroidism
Glucocorticoid deficiency
Reset osmostat

Intravascular vol
Hypoalbuminemia

Cardiac
failure

Third spacing:
burns, pancreatitis

UNa: >20 mmol/l

<10mmol/l

NS
Cirrhosis

UNa >20mmol/l

USG/ UOsm :N or reduced

increased

increased

Rx:

Isotonic saline

water restriction

Isotonic saline

USG urine specific gravity

Intravascular vol

UNa: <10mmol/l

USG/Uosm:

increased
colloid

Renal
failure

kwashiorkor

<10mmol/l

increased

<10mmol/l >20mmol/l

increased

USG 1.010

salt and water restriction

UOsm urine osmolality NS nephrotic syndrome

SIADH (syndrome of inappropriate ADH secretion) ADH induced water retention resulting in volume
expansion and natriuresis
Diagnosed by low plasma Na and osmolality
Urine not maximally dilute
Normal renal function
No evidence of inadequate Na intake or other source of Na loss
Absence of water retaining drugs
Absence of other causes of hyponatremia
Treatment: - water restriction, hypertonic saline for acute neurological complication

41

Drugs have no role in the management of SIADH in children

Associated with pain, pulmonary disorders, CNS disorders, drugs e.g. Vincristine, Cyclophosphamide,
Indomethacin, Carbamazepine, Minoxidil, calcium channel blockers

Hypernatremia
Definition: serum Na >150mmol/l. Aetiological differentiation is aided by clinical presentation
Etiology:
1. Sodium overload: Salt poisoning, hyper aldosteronism t
2. Inadequate water:
Inability to drink in response to thirst comatose or neurologically impaired patients, infants, high
environmental temperatures, lack of free access to water

Adipsia or essential hypernatremia:

- rare usually hypothalamic lesions
- no thirst in response to hypertonicity but ADH is released in response to non osmolar stimuli
- due to defect in ADH release in response to osmolar stimuli
- defect is destruction of the osmoreceptors but preservation of the supraoptic and
paraventricular nuclei where ADH is synthesized
- recurrent /persistent hypernatremia without thirst
- urine and plasma osmolality show no correlation
- ADH is however secreted normally in response to hypotension and hypovolemia
Low set point for ADH release (reset osmostat)
3.

Non renal water loss without replacement

4.

Renal water loss

Absence or inadequate secretion of ADH central diabetes insipidus (DI) head injury ,
infarction (Sheehans syndrome), tumours ( craniopharyngioma), histiocytosis, degenerative brain
disease, infections, hereditary (dominant), idiopathic
Impaired tubular responsiveness to ADH nephrogenic D: Chronic renal failure,
hypokalemia, hypercalcemia, damage to renal medulla sickle cell disease, nephropathies, renal
papillary necrosis, chronic pyelonephritis/ reflux nephropathy, congenital
Hereditary nephrogenic vasopressin resistant DI (VRDI) = congenital nephrogenic DI
2 types at the molecular level:
1. X linked mutation in gene for tubular V2 ADH receptor
2. Autosomal recessive mutation in gene for aquaporin 2 the distal tubule water channel

Symptoms of hypernatremia: Restlessness, irritability, muscle twitching, hyperreflexia, seizures, coma and
death. History of polyuria, polydypsia, gastroenteritis, salt poisoning, renal disease, dehydration, growth
failure
Examination: growth parameters, BP, hydration status, conscious level, and temperature. Children with
hypernatremic dehydration appear less dehydrated than they really are, intravascular volume is preserved
until late in the illness, and the skin has a doughy feel.
Investigations: electrolytes, urea, creatinine, bicarbonate, glucose, calcium and albumin, Hb, serum
osmolality, spot urine (ideally first morning void) for specific gravity, osmolality, microscopy and blood
protein
Hypernatremia may be complicated by hyperglycemia and hypocalcemia (see Hypernatremic
dehydration)

42

Evaluation of hypernatremia
Clinical examination
Dehydrated

Volume overloaded

Renal losses

Extrarenal losses

USG: < 1.005

<1.010 >1.015

UNa+: Variable
(mmol/l)
Diabetes
Insipidus

>20

nonosmotic
diuretics

variable

osmotic
diuretics

Increased total body Na

Sweat/ diarrhoea

pure Na gain

> 1.015

<1.010

UNa<10

UNa >20

excessive sweating
GI / respiratory losses

Na>H2Ogain

salt poisoning
NaHCO3overdose

primary
hyperaldos
teronism
hypokalemia
hypertension

Rx:

water replacement

water+ salt replacement

diuretics and
water
replacement

treat primary
condition

HYPERNATREMIC DEHYDRATION
Risk of cerebral oedema if rehydration is too rapid
Resusciation phase is as for other types of dehydration
Calculated water deficit rather than % dehydration is a more accurate means fo determining fluid
deficit as ECF and plasma volume are preseved fro loner in hypernatremia, and clinical assessment
may under estimate the degree of dehydration
Fluid requirements see sections (1) (2), (3) (4) in the treatment of dehydration (page 2)
1. H2O deficit (litres) =
Na initial Na desired x (0.6 x Wt in kg in children > 1 year of age)*
Na desired
*This represents total body water (TBW). In infants <1 year of age TBW = 0.75 x Wt in kg
Give water deficit over a period of days so that the serum sodium does not fall > 10mEq/l /24 hours
Fluids used D4.3 0.18 N saline, D5 in normal saline, ORF, milk.
DO NOT USE SODIUM FREE SOLUTION
1 Maintenance : 75% of usual calculated maintenance since hypernatremia provokes ADH
secretion

43

2
3
4
5

Ongoing losses: measured or estimated and replaced over 24 hours, every 4hours over the next 4
hours or as lost
N.B. subtract from the first 24 hours fluid the vomue used in resuscitation
Careful monitoring required. Repeat electrolytes at least every 12 hours. Reduce fluid intake if Na
falls too fast or increase if Na falls too slowly.
Salt poisoning with serum Na >200mEq/l may be treated with peritoneal dialysis with high
glucose (7.5%) and low Na dialysate

Potassium and bicarbonate replacement are as for other forms of dehydration.

Complications of hypernatremic dehydration: include hypocalcemia, hyperglycemia and seizures, so
check serum calcium and blood glucose regularly. Seizures may result from intracranial haemorrhage,
cerebral oedema or biochemical derangements.
Hypocalcemia: usually transient. If however symptomatic, start calcium infusion (See Disorders of
Calcium Metabolism).Remember that calcium and bicarbonate cannot be mixed.
Hyperglycemia: Is transient, does not require insulin and will resolve when hypernatremia is corrected.
Diabetes mellitus may be associated with hypernatremia and must be differentiated from the transient
hyperglycemia induced by hypernatremia. Hyperglycemia may cause underestimation of serum Na.
Correction of serum sodium for hyperglycemia
True serum Na mmol/l = [Blood glucose mmol/l] x 1.5 + measured Na mmol/l
5.5
POTASSIUM METABOLISM

The combination of hypokalemia and high plasma bicarbonate is more likely due to K+ depletion
than primarily to metabolic alkalosis which is rare.
Acute K+ loss causes more severe hypokalemia than chronic K+ loss
The combination of hyperkalemia and low plasma bicarbonate is more likely due to metabolic
acidosis than primarily to K+ excess.

Hypokalemia (serum K+ < 3.5mmol/l)

Without K deficit: Familial periodic paralysis, athletes
With K deficit

Reduced intake (UK+ <20mmol/l) - tea and toast diet, alcoholism, anorexia nervosa, starvation , clay
eaters, cellular incorporation of K in the treatment of megaloblastic anaemia, TPN
Renal K+ loss (UK+ > 20mmol/l
1. Increased activity of the Na/K exchange mechanism in distal nephron :
- Secondary hyperaldosteronism (hypertension associated)
- Cushings and steroids- mineralocorticoid effect on tubule (hypertension associated)
- Primary hyperaldosteronism
- ACTH treatment or ectopic ACTH production (hypertension associated)
- ? Bartters syndrome normotension
2. Excess Na for exchange at distal nephron diuretics inhibit Na reabsorption proximally
3. Reduced renal Na/H+ exchange --- increased Na/K exchange a) carbonic anhydrase
inhibitors, b) renal tubular acidosis c)metabolic acidosis
4. Reduced proximal tubular K+ reabsorption --- renal tubular failure:
- polyuric phase of ARF,
- osmotic diuretic DKA, mannitol (associated with dehydration and acidosis
- Fanconi syndrome

44

Non renal K+ loss (UK+ <20mmol/l)

1. Intestinal secretions: prolonged vomiting, diarrhoea, intestinal fistulae
2. Reduced K intake: chronic starvation reduced salt and water intake ---secondary
hyperaldosteronism
3. K redistribution: K loss into cells :glucose/ insulin, familial periodic paralysis (spontaneous K
entry into cells)
4. K loss from ECF by more than 1 route: alkalosis, pyloric stenosis and secondary alkalosis
Effects of hypokalemia
metabolic abnormal CHO metabolism, abnormal glucose tolerance, ? negative nitrogen balance
hormonal a) reduced aldosterone secretion, reduced insulin release
vasoconstriction, rhabdomyolysis
cardiac myogenic cell necrosis, myocardial fibrosis, ECG changes
neuromuscular ileus, weakness, quadraplegia, autonomic, insufficiency, postural hypotension
renal: K conservation, polyuria, polydipsia, increased ammonia production, oedema and Na retention,
hypokalemic nephropathy
For K replacement
1gm KCl = 13mEqK+
Mist KCl : 10 ml = 13.4mEq
IV K+ at 10 mEq/hr does not require ECG monitoring
IV K+ at > 40mEq / hr should only be done with ECG monitoring
Treatment: There is no formula to estimate K deficit. Correction of hypokalemia consists of:
providing maintenance K+ 2 mEq/kg/day (more in premature neonates0
estimating and replacing on going losses (spot urine sodium, GI losses)
estimating the deficit as a proportion of regular maintenance and replace by increasing maintenance by
50% or more depending of the severity of the hypokalemia
regular measurement of electrolytes, losses and clinical status to assess response to treatment
Treat the underlying cause of hypokalemia if possible

Hyperkalemia
In renal failure, serum K remains normal till GFR falls < 5mls/min
Symptoms and signs: weakness, paralysis, cardiac arrhythmias, partial depolarization (interferes with
neuromuscular transmission) due to changes in extracellular ion concentration
Etiology:
Pseudo hyperkalemia tourniquet, increased WBC, haemolysis
True hyperkalemia
1. Redistribution acidosis, hyperkalemi, periodic paralysis, Digoxin toxicity
2. Reduced excretion chronic or ARF, K sparing diuretics, reduced adrenal steroids (Addisons disease,
hypoaldosteronism (TTKG)
Selective impairment of K excretion SLE, renal transplant, SS.
Evaluation of Hyperkalemia
Renal function

------------------------- abnormal >>>>> renal failure

If normal check for metabolic acidosis

45

Present >> renal tubular acidosis check UpH

>>mineralocorticoid deficiency check TTKG = UK//U/P Osm
serum K+(See Chapter 1)
>> severe dehydration
If absent -perform Urinalysis
+hemastix >>>>>>>>>>> rbc on microscopy true haematuria renal disease
>>>>>>>>>>> no rbc on microscopy check for hemolysis
serum not haemolysed >>>>>>>>>>> myoglobinuria
serum haemolysed >>>>>>>>>>>>>>haemoglobinuria
Treatment:
General: See Chapter 10
Specific: Treat cause

POLYURIA
Definition: Passage of abnormally large urine volumes (>4cc/kg/hr)
Etiology
Excessive water intake e.g. psychogenic polydipsia
Excessive water output diabetes insipidus
Excessive urinary solute load e.g. diabetes mellitus, osmotic diuretics, salt wasting syndromes
nephropathy or mineralocorticoid deficiency, diuretic phase of renal failure (urea loss), hypercalcemia
(calcium loss)
History: Predisposing factors as above, salt craving, diuretic use, fluid intake, urine volume. Distinguish
between polyuria and increased frequency of micturition without polyuria.
Examination: Growth parameters, blood pressure, hydration status, visual fields and CNS examination,
and genitalia for ambiguity.
Investigations:
Urine volume/24 hour or as a single void
Urine dipstix : glucose, protein, blood / microscopy (spun) cells , casts / specific gravity and
osmolality random or water deprived
Urine pH (by electrode in Chem. Pathology) RTA
Hb, urea, electrolytes, creatinine, bicarbonate, calcium, albumin (glucose of glycosuric)
If central DI : cranial CT, visual fields, SXR, T4, TSH, R3RU, a.m. and p.m. cortisols +/- growth
hormone
If nephrogenic DI estimate creatinine clearance and protein excretion from spot urine and serum
values ( see Chapter 1 Assessment of Renal Function), renal ultrasound +/- IVP, +/- renal scan
To calculate Uosm (urine osmolality) from USG
Uosm (mOsm/kg H20 ) = (USG 1.000) x 40,000

46

EVALUATION OF POLYURIA
Measure urine volume
Single void
Normal to low

High

Increased urinary frequency

Possible polyuria

Not polyuria
Random USG

< 1.005

1.010

Diabetes insipidus / psychogenic polydipsia

Could be normal

Water deprivation test

Overnight fast

USG < 1.005

Diabetes insipidus (DI)

USG >1.012
Normal
or
Possible psychogenic polydipsia

USG 1.010
Renal disease

USG > 1.015

Normal

Vasopressin stimulation
USG increased
UVol decreased

USG unchanged
UVol unchanged

Central DI

Nephrogenic DI

Rx: Vasopressin

Rx: Low salt diet, Indomethacin or Hydrochlorothiazide

USG Urine specific gravity UVol urine volume

NB: If results are equivocal request Endocrine or Nephrology consultation
WATER DEPRIVATION TEST
The water deprivation test (standard 9 hours and prolonged 17 hours) is used to differentiate between
diabetes insipidus and psychogenic polydipsia. The indications include polyuria, polydipsia and a low urine
specific gravity.
Standard
Patient has:
No fluids after 6 a.m.
Dry breakfast by 7.30a.m
NPO at 8.00a.m. for test duration

47

Prolonged
Patient has:
No fluids after 10.00p.m.
Dry breakfast by 7.30 a.m.
NPO at 8.00a.m. for duration
Standard:
Vital signs pulse, resp. rate, BP - q1hourly
Patients to be weighed at start of test
Infants (<3 years) weighed hourly
Children> 3 years) weighed 3 hourly
Urine samples to be taken at start of test
Infants catheterize and so samples q 2 h
Children test each sample voided
Urine tested for specific gravity, glucose and protein- volume recorded
Blood samples taken at 9.00a.m. and 3.00 p.m. and 4.p.m.
Tests requested blood, urea, electrolytes, glucose in order to calculate serum osmolality (POsm)

To calculate Serum osmolality (SOsm)

SOsm (mOsm /kg H20) = (Na (mmol/l) x 2) + urea (mmol/l) + glucose (mmol/l)
Prolonged:
Should not be done on an infant or a child who is strongly suspected clinically of having DI
It is useful in differentiating partial DO from psychogenic polydipsia
Urine samples taken at start of test and then 4 hourly until 8.00 a.m. then follow standard protocol. All
urine volume recorded
Vital signs q4 h overnight then follow standard protocol
Weigh at start of test
Blood sample at 10.00 p.m. and 6.00a.m. then follow standard protocol
At 3.00 p.m. if patient has been unable to concentrate urine > 1.012 then give:
a) Aqueous Pitressin (1:1,000) 0.1 unit /kg to a maximum of 5 units IM
OR
b) DDAVP 0.1 ml intranasally
The IM route is preferred.
At 1 hour and 2 hours after exogenous ADH (above) do:
Urine samples for specific gravity, glucose, protein
Blood samples for urea and electrolytes and glucose
NB discontinue test if :
a) Weight loss >3%
b) Patient becomes hypotensive with postural hypotension
c) Patient becomes distressed
Results of Water Deprivation Test
Central DI:
SOsm increased
Serum Na increased
USG low. After ADH USG
increases
Serum Na increased
USG low. After ADH USG still
Nephrogenic DI : SOsm increased
low
Psychogenic polydipsia urine concentrates slowly as dehydration occurs

48

References:
1. Disorders of Water Metabolism. Schrier RW, Berl, T in Renal and Electrolyte Disorders (1980) 2nd
edn. Shrier ed. Little Brown and Company, Pub.
2. Serum sodium abnormalities in children. Ped Clin N Am (1982) 29: 907-932
3. Differential diagnosis of polyuria and diabetes insipidus. Singer I, Med Clin N am (1981) 65: 303-320
4. Pediatric Nephrology (1999)p 133-141. 4th edn. Barratt, Avner, Harmon eds. Lippincott, Williams and
Wilkins pub
5. Clinical Chemistry in Diagnosis and Treatment (1975) p 30-74. Zilva J, Pannall PR.

49

CHAPTER 7
UROLITHIASIS AND DISORDERS OF CALCIUM METABOLISM
Etiology
1. Calcium lithiasis (commonest)

Normocalcemic hypercalciuria
Idiopathic hypercalciuria absorptive or renal
Distal renal tubular acidosis
Drug induced (Furosemide)
Hypercalcemic hypercalciuria
Increased calcium reabsorption from bone primary hyperparathyroidism, immobilization,
adrenocorticosteroid excess, adrenal insufficiency, osteolytic metastases
Increased GI absorption e.g. hypervitaminosis D, idiopathic hypercalcemia of infancy,
sarcoidosis , milk-alkali syndrome
2. Hyperoxaluria

Primary autosomal recessive.

Type 1 more severe than type 2 associated with glycollic aciduria and renal failure

Type 2 with glyceric aciduria

Secondary

Dietary oxalate excess

Hyperabsorption of oxalate intestinal disease (inflammatory bowel disease) , lowered

intestinal Calcium levels

Excess ascorbate (Vit C) intake

Ethylene glycol ingestion

Methoxyflurane anaesthesia

Aspergillosis

Vitamin B6 deficiency
Mild metabolic hyperoxaluria
3. Hypocitraturia
Seen in distal RTA, malabsorption syndromes associated with enteric hyperoxaluria. Citrate is a
urinary stone inhibitor. Citrate excretion is reduced by thiazide diuretics, acidosis and hypokalemia.
4. Uric acid lithiasis / hyperuricosuria
Often associated with calcium oxalate stones. Predisposing factors; urine pH <6, decreased fluid
intake, hyperuricemia (gout, Lesch Nyan syndrome, tumour lysis syndrome)
5. Struvite (infection, triple phosphate) lithiasis magnesium, ammonium phosphate and calcium
phosphate (apatite) sometimes staghorn calculi -associated with urinary tract infections caused by
urease producing organisms
6. Inborn errors of metabolism
Cystinuria inborn error of metabolism diagnosed by aminoaciduria of Cystine, Ornithine,
Arginine and Lysine
Hereditary xanthinuria, / Orotic aciduria
7. Drug related
8. Hypomagnesuria (magnesium is and inhibitor of Calcium oxalate stone formation
9. Chronic hypovolemia

History

50

Pain, haematuria, fever, UTI symptoms, failure to thrive, history of recurrent UTI, especially with
Proteus, recurrent abdominal pain especially in the flank with loin to groin radiation. Recurrent or
persistent gross haematuria (idiopathic hypercalciuria is a common cause).
Positive family history of renal stones
Ask re: diet, excessive Vit C and D intake, drug ingestion
High oxalate foods: cocoa, Ovaltine, tea, green beans, beets, celery, eggplant, okra, green peppers,
spinach, all kinds of berries, purple grapes, fruit cocktail, oranges, orange peel and orange juice,
tangerine and tangerine juice, fruitcake, grits, wheat germ, nuts - almond, pecans, cashews,
peanuts and walnuts, chocolate cocoa, vegetable soup, tomato soup, marmalade.

Examination
Growth parameters, blood pressure, abdomen for masses e.g. distended bladder or kidneys.
Investigations
Urine
Cleaned MSU for culture, unspun for microscopy, urinalysis for crystals, pH, blood, protein, wbc
and rbc
Spot urine X 3 for calcium, uric acid, creatinine, one of which should include a spot urine phosphate
which can be combined with the serum phosphate and serum creatinine to calculate the tubular
reabsorption of phosphate TRP
If absorptive hypercalciuria is to be distinguished from renal hypercalciuria, do spot urine
calcium/creatinine on early morning fasting urine sample. This is just a screening test.
Spot urine for amino acid screen (Chemical Pathology) to rule out cystinuria and other
aminoacidurias
24 hour urine oxalate (and creatinine on the same sample if possible in the lab) done abroad privately
24 hour urine uric acid and creatinine, 24 hour urine calcium (and creatinine if possible in the lab) to
verify the increased urinary excretion documented on spot urines or to prove excess urine solute
excretion where suspected but unproven by spot samples. 24-hour urine creatinine with the measured
solute helps to assess completeness of the collection. 24-hour urine calcium collected in acid washed
bottle.
+/- 24 hour urine citrate and creatinine
stone analysis
Blood: urea, creatinine, electrolytes, bicarbonate, calcium (without tourniquet), phosphate, alkaline
phosphatase, serum albumin, uric acid , (PTH levels if available)
Radiology;
Plain abdominal X-ray (about 90% of stones are radioopaque calclium oxalate, calcium phosphate,
struvite stones). Cystine stones are less opaque and uric acid stones are non opaque
Renal ultrasound for obstruction and stone visualization pyelectasis takes >6 hours to develop- U.S
is less sensitive than plain XR for stone visualization
Intravenous Urogram (IVU) for stone localization the best test. In acute ureteral obstruction there
is a delayed dense nephrogram. On delayed films, there is renal enlargement and pyelo and caliectasis
+/- ureterectasis
CT scan of kidneys for oxalate, phosphate, struvite, cystine, uric acid calculi.
Doppler US urine jet from ureteric orifice into the bladder suggests stone is non obstrucitve not
always reliable
+/- MCUG if urological abnormalities likely
If hyperparathyroidism or rickets present X ray L wrist bone age and L hand penetrated view for
rickets and evidence of hyperparathyroidism
Tubular reabsorption of phosphate (see normal values)
Normal >80% Hyperparathyroidism <80%

51

Normal Urinary Solute Excretion rates

Calcium
< 0.1mmol/kg/day

.
<4mg/kg/day

Urine calcium:creatinine ratio

< .00074mmol/l:umol/l

<0.21:1 mg/dl:mg/dl

Uric acid

< 0.06 mmol/kg/day

<815mg/1.73m2/day
<35mg/kg/day

Urine uric acid:creatinine ratio

<0.00067 mmol/l:umol/l

Oxalate

< 0.46mmol/1.73m2/day

Oxalate:creatinine ratio

< 2mg/kg/day
In primary hyperoxaluria
24 hr urine oxalate
>1mmol/1.73m2/day
0.00012mmol/l:umol/l

< 1year age:<0.21mg/mg/creatine

1-12 years: <0.12mg/mg creatinine
>12years: <0.07mg/mgcreatinine
In primary hyperoxaluria
24 hr urine oxalate
>100mg/ 1.73m2/day
0.08 mg/dl:mg/dl

Cystine

<75mg/g creatinine

Citrate

>180mg/g creatinine

Magnesium

> 88mg/1.73m2/day

Creatinine*

Creatinine clearance

135-175umol/kg/day (child
and adult female)
175-220umol/kg/day (adult
male)
>80ml/min/1.73m2

*low creatinine excretions suggests incomplete collection

Handbook of Pediatric Urology (1997) p237. Baskin, Kogan, Duckett, eds.
Stone Disease Diagnosis and Management (1987), p320. SN Rous SN,ed.
Pediatric Nephrology 4th Edn (1999) p938 Barratt, Avner, Harmon, eds.
Conversion factors:
Urate (g/day) x 5.948 = mmol/day
Oxalaate (mg/day) x 11.11 = mol/day
Creatinine (g/day) x 8.89 = mmol/day
Cystine (mg/day) x 4.161 = mol/day
Calcium (mg/day) x .02495 = mmol/day
Management
Medical:
Acute presentation: Analgesic (e.g. Baralgin), adequate hydration IV or po with 1 - 2 times
maintenance fluid. If renal failure or significant obstruction present, these must be addressed
specifically and fluid management adjusted as appropriate.
Antibiotics if UTI suspected.
Catherization of bladder if bladder outlet obstruction. Nephrology and Urology consultation.
Maintenance therapy

52

General :
Relief of obstruction, removal of stones
High fluid intake at least 1 times maintenance fluids
Follow up plain abdominal X-rays for further stone formation (if opaque), with renal
ultrasound for evaluation of persistent of obstruction, progressive nephrocalcinosis or
urolithiasis every 6 months 1 year.
Monitor excretion of urinary solute by spot urines and/or 24 hour urine collections every 3 6
months after starting treatment to determine if treatment is adequate.
Specific:
Idiopathic hypercalciuria: In children, the distinction between absorptive and renal hypercalciuria tends
to be more theoretical than practical. Both are most commoly treated as follows.
Low sodium intake
1. High fluid intake (1 - 2 times maintenance)
2. Thiazide diuretics reduces calcium excretion in both absorptive and renal hypercalciuria.
Hydroclorothiazide 2 mg/kg/day or Bendrofluazide 0.2mg/kg/day (if urolithiasis present), however if
haematuria is the only presentation of hypercalciuria, chronic thiazide therapy is not absolutely indicated).
Side effects hypokalemia, hyperuricemia, dehydration
Follow-up blood urea, creatinine, electrolytes and creatinine and uric acid
Monitoring as above
Hypercalciuria:
with hypercalcemia treat hypercalcemia and its cause
with distal RTA treat acidosis ideally with potassium citrate.
Uric acid calculi
Dietary purine restriction
High fluid intake
Alkalinize the urine preferably with K citrate rather than Na bicarbonate to reduce risk of calcium
oxalate stone formation pH should be 6-6.5. Give doses throughout the day with the last dose at
bedtime. If urine pH >7, risk of precipitation of calcium phosphate.
K citrate (mist pot cit) 1 3 mEq/kg/day divided t.i.d
Na bicarbonate 1 2 mEq/kg/day divided t.i.d.
Allopurinol (for hyperuricemia, or recurrent uric acid stones despite other measures of control)
Allopurinol 5 -10 mg/kg/day(t.i.d)
Treat concomitant hypercalciuria if present and monitor uric acid excretion and renal function as described
or hypercalciuria.
Hyperoxaluiria General : dietary oxalate restriction and high fluid intake, treat bacterial overgrowth,
underlying bowel disease, and uric acid calculi if present. Monitor renal function and oxalate excretion
periodically as described for hypercalciuria.
Primary hyperoxaluria reduce dietary oxalate, hydrochlorothiazide 2 mg/kg/day, large doses of
inorganic phosphate ( if no renal failure), Pyridoxine, possibly magnesium oxide.
Enteric hyperoxaluria reduce dietary oxalate, give aluminum hydroxide and cholestyramine to
reduce oxalate absorption), K citrate, Mg and Ca supplements
Hyperuricosuric calcium oxalate stones low sodium diet, increased fluids, dietary purine (protein)
restriction, allopurinol if intolerant of dietary restriction, K citrate supplements to inhibit Ca oxalate
crystal formation (Urologic Clinics of North Am 1997)
Struvite calculi
Surgical removal
Treat infection 1-2 weeks of therapeutic antibiotics, followed by prophylaxis at 50% of the usual
dose for 3 months. Monthly urine cultures. When sterile for 3 months discontinue prophylaxis.
?urease inhibitors

53

Cystine calculi
very high fluid intake day and night, aiming for urine output of 2 litres (child), 3 4 litres (adults)
Alkalinization till urine pH is >7.5 in the morning
Na bicarbonate 2 3 mEq/kg/day (t.i.d. q.i.d)
K citrate 1 3 mEq/kg/day (t.i.d. q..i.d)
D penicillamine30 mg/kg/day (given q.i.d.) used to dissolve stones when alkalinization and increased
fluids have failed. Supplement with vitamin B6
Monitor renal function and cystine excretion periodically to assess adequacy of therapy.
HYPOCALCEMIA
Definition:
(a) Full term serum calcium <1.9mmol/l
Preterm - serum calcium <1.7 mmol/l
Older child serum calcium <2mmol/l
Or Ionized calcium <0.75mmol/l
[Residents Handbook of Pediatrics (1987) p 398]
Etiology
Neonatal period prematurity, low birth weight, Di George syndrome, severe sepsis, intracranial
haemorrhage, diabetic or hyperparathyroid mother, poor calcium intake, transient neonatal
hypoparathyroidism, exchange transfusion.
General Vitamin D deficiency, renal failure, steatorrhoea, steroid or furosemide therapy, hypo or
pseudo hypoparathyroidism
Treatment
a) If symptomatic e.g. seizures, tetany, this is an emergency. Treat by IV route only.
b) IV calcium at 0.2 mEq Ca2+/kg/hr
c) Repeat serum calcium level 4 hours after starting the infusion and adjust according to value. Once
serum calcium level is >2mmol/l, reduce infusion rate slowly . Increase infusion rate if serum calcium
falls. Start measures (d) and (e) and attempt to wean off IV when serum calcium normalizes
d) Start oral calcium at 2 mEq/kg/day
e) Rocaltrol (Calcitrio) 1,25 dihydroxy Vitamin D3
Newborns 0.10 0.15 ug/kg/day reduced to 0.025 0.05ug/kg/day after 3 4 days
Older children 0.025 0.05ug/kg/day
Watch that IV calcium does not extravasate as serious burns may occur. Never give Calcium IM or
subcutaneously
IV Calcium infusion: using 10% Calcium gluconate (any other intravenous Calcium preparation may be
used but the volume of the preparation required to deliver 0.2mEq/kg/hr must be calculated for each
product).
To deliver 0.2mEq/kg/hr of 105 Calcium gluconate :
Make a 1:5 dilution of 10% Calcium gluconate with 5% glucose water = 0.1mEq Ca2+ /ml
Calcium dose in this dilution = 2cc/kg/hr (0.2mEq/kg/hr)
HYPERCALCEMIA
Definition: serum calcium >3mmol/l
Treatment:
1. If secondary to Vitamin D or Calcium supplements discontinue immediately
2. Low calcium diet
3. Fluids at 2 times maintenance usually as normal saline
4. Corticosteroids e.g. hydrocortisone 4 mg/kg/dose IV q 4 6 hourly
5. Furosemide 0.5 1 mg/kg IV q 4 6 hourly (avoid dehydration)

54

6.
7.

Watch for hypokalemia, hyponatremia,

Monitor serum calcium and electrolyte levels frequently

Some calcium salts and their approximate calcium content

Table gives the amount of elemental calcium per gram of preparation, so in order to calculate the # mEq
Ca2+ in your preparation, the # mg of CaCO3 per unit of preparation must be known.
e.g Regular Tums 500mg CaCO3 / tablet
- 1 gm CaCO3 / 2 tablets = 20mEq Ca2+
- 1 tablet = 10mEq Ca2+
Approximate calcium content per g
Calcium salt

mg

mmol

mEq

Calcium acetate (anhydrous)

253

6.3

12.6

400

10.0

20

273

6.8

13.6

211

5.3

10.5

66

1.6

3.3

82

4.1

89

2.2

4.5

191

4.8

9.5

184

4.6

9.2

147

3.7

7.3

130

3.2

6.5

129

3.2

6.4

51

1.3

2.5

131

3.3

6.5

233

5.8

11.6

388

9.7

19.3

399

10.0

19.9

135

3.4

6.7

78

1.9

3.9

Calcium carbonate
Calcium chloride (dihydrate)
Calcium citrate(tetrahydrate)
Calcium glubionate(monohydrate)
Calcium gluceptate(anhydrous)
Calcium gluconate (monohydrate)
Calcium glycerophosphate ( anhydrous)
Calcium lactate (anhydrous)
Calcium lactate (trihydrate)
Calcium lactate(pentahydrate)
Calcium lactate gluconate (dihydrate)
Calclium lactobionate (dihydrate)
Calcium laevulinate (dihydrate)
Calcium hydrogen phosphate (dihydrate)
Calcium phosphate (Ca3(PO4)2)
Calcium phosphate (10CaO. 3P2O5.H2O)
Calcium pidolate (anhydrous)
Calcium sodium lactate( tetrahydrate)
Martindale* the Extra Pharmacopoeia 31st Edition 1996 page 1178

55

References:
1. Stone disease diagnosis and management. (1987) pp 150, 182, 347 378. Rous SN ed. Grune and
Stratton pub.
2. Urolog Clin N Am (1997) 24: 135-147, 147 162, 81-86, 97-116
3. Pediatric Nephrology (1999) pp 938-939. 4thedn. Barratt TM, Avner ED, Harmon WE eds. Lippincott,
Williams and Wilkins pub.
4. Pediatric Nephrology (1989) 3::317 331
5. Martindale The Extra Pharmacopoeia (1996) 1178. 31st edn.

56

CHAPTER 8
URINARY TRACT INFECTIONS
DEFINITIONS:
Urinary Tract Infection (UTI):
Significant bacteriuria with or without urinary tract symptoms
Asymptomatic bacteriuria:
Significant bacteriuria without symptoms
Acute cystitis:
Symptomatic UTI localized to the bladder
Acute pyelonephritis:
Symptomatic UTI localized to the renal parenchyma
Significant bacteriuria:
Any growth on a bladder tap urine sample (except up to 2,000 -3,000 colonies /ml of coagulase
negative staph
> 103colonies /ml (catheter sample - CSU) in a normal child
> 105 colonies /ml in a CSU from a child on clean intermittent catherization (as per voided urine below
> 105 colonies /ml of voided urine (MSU or clean catch urine) on > 2 voided samples showing the
same organism with the same sensitivity
Pyelonephritis : is present in >75% of children < 5 years of age with febrile UTI, and causes renal scarring
in 24-64% of children < 5 years of age with UTI. Most UTI's resulting in scarring or reduced renal growth
occur in children <age 4 years. Children < age 3 years often have recurrent infections (up to 1/3 of which
are asymptomatic) and therefore are at greater risk of renal scarring.
Focal renal scarring secondary to childhood pyelonephritis results in: 23% risk of hypertension, 10%
risk of end stage renal disease (ESRD), 13% risk of toxaemia in pregnancy.
AETIOLOGY OF UTI:
GRAM NEGATIVE
E. coli*, Klebsiella, Proteus, Pseudomonas, Enterobacter, Citrobacter, Morganella, Serratia,
Providentia
GRAM POSITIVE
Staphylococcus, Enterococcus
PREDISPOSING FACTORS:
Host factors - obstruction (mechanical / neurogenic), vesicoureteric reflux, constipation, voiding
dysfunction, foreskin, hypercalciuria / stones, parasites
Host -non factors - improper wiping, bubble bath
Bacterial factors - adherence factors, capsular antigen, haemolysin, resistance to serum
bactericidal activity
HISTORY:
Straining, poor stream - outlet obstruction
Gait disturbance, enuresis, encopresis - neurogenic bladder
Constipation, urgency, enuresis, squatting - dysfunctional voiding
Recurrent PUO - unrecognized UTI
In neonate - sepsis, jaundice, failure to thrive, vomiting, straining with micturition, haematuria
In older child - frequency, dysuria, enuresis, fever , offensive urine, haematuria, loin pain
EXAMINATION:
Growth parameters, anaemia - chronic illness
Blood pressure - hypertension
Abdominal examination - obstructive uropathy, constipation
External genitalia - meatal stenosis, labial adhesions, vulvovaginitis
Sacral anomalies, anal wink, lower limb reflexes - neurogenic bladder

57

DIAGNOSTIC PITFALLS - symptoms/signs incorrectly suggestive of UTI

Pink diaper syndrome - amorphous urates on diaper - salmon coloured powder
Normal straining sounds during infant voiding
Urethritis, vulvovaginitis
Dysfunction voiding - small bladder, unstable bladder, large bladder - may have frequency, urgency,
enuresis
Daytime urgency, frequency syndrome (hysterical voiding of childhood) - daytime urinary frequency
without enuresis- emotional in aetiology
INVESTIGATIONS:
Urine culture preferably bladder tap (children <2 years) or CSU if only a single sample is possible before starting
antibiotics
CONTRAINDICATIONS TO BLADDER TAP:
1. Patients e.g. cardiacs for whom infective endocarditis prophylaxis would have been needed
for genito-urinary instrumentation
2. Patients with coagulopathies eg haemophilia
3. Patients with pelvic kidney
4. Empty bladder
CONTRAINDICATIONS TO CSU

Patients in category (1) above

Infections of the genital / peri - urethral area

Voided urines have a high false positive rate and are conclusive only if negative. If voided urines are used
to diagnose UTI, there should be at least 2 samples, both showing the same organism with the same
sensitivity pattern. The external genitalia should be cleaned and wiped dry. When a urine bag is applied it
should be changed at least every 30 minutes to avoid external contamination.
Samples collected should be processed promptly. If there is a delay in delivery to the laboratory, the sample
should be refrigerated to avoid bacterial multiplication, and false positive results. Samples should be
processed within 48 hours of collection.
Immediate diagnostic aids - these aid with the diagnosis but only a urine culture can diagnose a UTI:
Multistix (Ames ) + test for leukocytes, nitrates and >trace blood - suggestive of UTI
Urine microscopy - any bacteria on an uncentrifuged sample is highly suggestive of UTI
Haematuria and / or pyuria do not = a UTI
UTI may be present without pyuria
SUPPLEMENTAL TESTS
Blood urea, creatinine, electrolytes, CBC (+/- Hb electrophoresis), (+/- Blood culture)
UTI controversies re: investigation:
In the First World where full investigation for UTI from infancy has been practiced for at least a decade,
the recommendation now is that no radiological imaging is required in children > 2 years of age with the
clinical diagnosis of cystitis (acute dysuria, without high fever, with normal concentrating ability) if there is
no suspicion of UTI in the history and if there is a high detection rate of infant pyelonephritis in the
community. (Hansson s, Joday U - Pediatric Nephrology 4th edition 1999 - 844). In Jamaica infant UTI's
are still being missed or uninvestigated. The policy of no imaging studies in the girls < 2 years is based on
the observation that radiological abnormalities are rarely seen in this group, but, in societies, like Jamaica,
with a low detection rate of UTI's in infants and small children, it must be stressed that children with
previously undetected UTI and renal scarring or vesico-ureteric reflux may present later with afebrile
symptomatic infections, and would be missed if this protocol is applied to Jamaica. Therefore IN
JAMAICA, for the time being, ALL CHILDREN WITH UTI REQUIRE RADIOLOGICAL
INVESTIGATION.

58

ABOLUTE ESSENTIALS:
All children (males and females)must be investigated, after the first UTI
Ensure that the diagnosis of UTI is based on strict culture criteria and not just on symptoms or
diagnostic aids alone
AIMS OF INVESTIGATION:
Diagnose obstructive uropathy eg - PUV, PUJ and VUJ obstruction, neurogenic bladder
Diagnose vesico-ureteric reflux (16% of Jamaican children with UTI have VUR )
Obstructive uropathy, reflux nephropathy, renal dysplasia account for 59% of the cases of childhood
CRF in Jamaica at UHWI (Dec1984-- October 1996)
RADIOLOGICAL INVESTIGATIONS:
Renal ultrasound (all children) - request renal lengths and compare with age and weight related
normal values (see Chapter 1)
Micturating cystogram (MCUG) - contrast
Age <5 years or any age if abnormal examination or abnormal renal ultrasound
Performed when the urine is sterile
ALWAYS LOOK AT THE MCUG YOURSELF - IF IT LOOKS ABNORMAL - eg dilated
or irregular posterior urethra or bladder - DISCUSS WITH PAED NEPHROLOGIST / PAED
SURGEON
Renal scan (DMSA)- renal scarring, or (locally available) Glucoheptonate renal scan- renal
scarring and function
To assess renal function, detect pyelonephritis and renal scarring
Indications: abnormal MCUG or ultrasound , recurrent UTI, febrile UTI, suspected acute
pyelonephritis
If obstruction suspected request Glucoheptonate renal scan with Lasix
Indirect radionucleide cystography - voiding phase of the renal scan - in children who can void on
request - is the most sensitive means of detecting vesico-ureteric reflux, but does not give good
anatomical definition so cannot replace the standard MCUG
TREATMENT Supportive - analgesics, increased fluids, correct underlying cause, correct constipation
LOWER UTI (CYSTITIS) - see table
Broad spectrum antibiotics - Trimethoprim / sulphamethoxazole, Amoxil, Augmentin, oral
cephalosporins, Sulphonamides, Nitrofurantoin
Duration of treatment controversial - conventional treatment - 10 days - RECOMMENDED
Shorter courses : single dose, 1,3, or 5 days - only for uncomplicated ITO (normal tracts) , not for the
first UTI, higher recurrence rate and need good follow-up I DO NOT RECOMMEND THE
ABBREVIATED ANTIBIOTIC COURSES
Amoxacilllin
Amoxil Clavulinate (Augmentin)

ORAL TREATMENT OF UTI

40-50mg/kg/dy (t.i.d.)
50mg/k /dy (bid)- AUGMENTIN bd preparation
50mg/kg/dy (t.i.d.) - Generic CURAM

Cephalosporin
Cefixime
Cefpodixime
Cefproxil
Cephalexin
Loracarbef
Cefuroxime
Cefaclor (Ceclor)
Nitrofurantoin * not in infants<6 weeks and in renal failure

8mg/kg/dy (b.i.d.)
10mg/kg/dy (b.i.d.)
30mg/kg/dy (b.i.d.)
50-100mg/kg/dy (q.i.d. or t.i.d)
15-30mg/kg/dy (b.i.d.)
60mg/kg/dy(b.i.d.)
40mg/kg/dy (t.i.d.ApoCeclor , b.i.d. Ceclor)
3mg/kg/dy(q.i.d)

59

ACUTE PYELONEPHRITIS - see table

Outpatient management
Nontoxic children and infants > 3 months old
If compliance expected
Initial 1-2 days of long acting 3rd generation Cephalosporin (IM Ceftriaxone), then 10-14 days of oral
antibiotics, or total of 10 - 14 days of parenteral antibiotics depending on severity and clinical progress.
In patient management
Toxic children and infants < 3 months old
Amoxil and an aminoglycoside or new 3rd generation Cephalosporin eg Cefotaxime, Ceftriaxone
Parenteral 10 -14 days ( neonate)
Parenteral till afebrile for 1-2 days then po to complete 10-14 days or parenteral for total of 10-14 days
depending on severity of illness and clinical response.
PARENTERAL TREATMENT OF UTI
Ceftriaxone

20 50mg/kg od /dy (age 1-14 days)

75mg/kg/dy (o.d. or q 12 h) (age15 days 1 2 years)
1 2 g /dy (od ) (adult or weight > 50 kg)

Cefotaxime
Ceftazidime (covers Pseudomonas and Enterobacter)
Cefazolin
Gentamycin
Tobramycin
Ticarcillin
Ampicillin
Augmentin

150mg/kg/dy (q6h-q8h)
150mg/kg/dy(q6h-q8h)
50mg/kg/dy (q8h)
5-7.5mg/kg/dy (q12-8h)
5mg/kg/dy (q8h)
300mg/kg/dy )q6h)
100mg/kg/dy (q6h)
30mg/kg/dy (q8h) (older infants and children)
30mg/kg/dy(q12h) (prems and full terms in perinatal period)

FOLLOW-UP INVESTIGATIONS
Urine culture - 2 days after starting, 2 days after ending treatment and at intervals thereafter for about
1 year
Monitor urea, creatinine and electrolytes when treating acute pyelonephritis especially with
aminoglycosides
After 1st UTI treatment has ended, start antibiotic prophylaxis until
investigations have been completed and found to be normal
until age 1 year in infants < 1 year (high risk of renal scarring)
Indications;
vesico-ureteric reflux
recurrent symptomatic UTI (>3/year)
obstructive uropathy, voiding dysfunction
before initial radiological evaluation
neonates and infants <1 year with febrile UTI and inflammatory changes on renal scan (scar risk)
Drugs - neonates: Amoxil, Cephalosporins, Older child - Cotrimoxazole, Nitrofurantoin (mainly)

60

PROPHYLACTIC ANTIBIOTICS
Trimethoprim /SMX
Trimethoprim
Nitrofurantoin
Sulphisoxazole
Nalidixic acid (not neonate)
Cefadroxil (Duricef)
Cefalexin (Ospexin)
Amoxil
Ciprofloxacin
Pivmecillinam
Pivmecillinam/pivampicillin

2mg TMP / 10mg SMX /kgnocte

2mg/kgnocte
1-2mg/kg nocte
10-20mg/kg/dy (b.i.d)
30mg/kg/dy (b.i.d.)
3-5mg/kg/dy (nocte)
125mg or 250mg nocte (up to 15 mg/kg nocte)
10mg/kg nocte (neonates)
25mg/kg/dy (bi.d) - neonates
1mg/kg/dy(nocte)
3-5mg/kg/dy
3-5mg/kg/dy (Pivmecillinam)

INDICATIONS FOR REFERRAL

Abnormal physical examination or investigations
Recurrent UTI
Refer to Paediatric surgeon / paediatric urologist : obstructive uropathy
Refer to Paediatric nephrologist - all other pathology
Always ask for advice if uncertain of management
DO NOT REFER EVERY CHILD WITH UTI TO POPD Renal - ONLY THOSE WITH
PROBLEMS

References:
1. Pediatrics (1999) 103:843-852- American academy of Pediatrics - Committee on Quality Improvement
- subcommittee on Urinary Tract Infection
2. Pediatric Nephrology 4th edition Barratt, Avner and Harmon editors (1999): 835-850
3. Pediatr Clin N Am (1997) 44:1133- 1169. Urinary Tract Infections in Children. Epidemiology,
evaluation and management.
4. Pediatr Clin N Am (1997) 44: 1171-1190.Vesicoureteral reflux

61

CHAPTER 9
ENURESIS AND OTHER VOIDING DISORDERS
Definition:
The involuntary passage of urine in a child old enough to have attained bladder control.
Approximately 98% of children are dry by day at age 4 years and 70% are dry by night at that age.
Nocturnal enuresis uncontrolled micturition during the night in a child over the age of 5 years, occurring
> once /week.
Diurnal enuresis daytime wetting beyond the age of 5years the age beyond which reliable daytime
dryness is expected to have been achieved.
Enuresis
Classification :
Diurnal
Nocturnal
Diurnal and nocturnal
All of the above subdivided into:
Primary incontinence in a child in whom bladder control has never been attained
Secondary incontinence 6 months to 1 year after continence has been achieved
NOCTURNAL ENURESIS
Primary : - Incidence : 10% of 5 year olds are wet at night but only 1% of 15 year olds have this problem.
It resolves spontaneously with time 15% of bedwetters over the age of 6 years will become dry each year
without intervention (spontaneous cure rate of 15% after age 6 years).
Another classification of nocturnal enuresis is based on EEG and cystometric readings during
nocturnal enuresis (Scan J Urol Nephrol, Vol31,1997, Suppl 183 (7-10).
Type 1 -due to mild arousal disturbance. When the bladder becomes full during sleep, there is
evidence of arousal on the EEG, but enuresis occurs without the subject awakening (no inhibitory
central response or awakening)
Type II a - caused by server disturbance in arousal. Even if the bladder is full there is no EEG
response and enuresis occurs without any indication of arousal.
Type II b due to a latent neurogenic bladder disorder that is only manifested during sleep.
Uninhibited bladder contractions are evident on the cystometrogram when the subject is asleep (but not
on awakening) and enuresis occurs without EEG response.
Physiology of bladder control
1. Detrusor muscle smooth involuntary 3 layers
2. Internal sphincter continuation of the detrusor muscle parasympathetic - involuntary - S 2,3,4
3. External sphincter part of the urogenital diaphragm pudendal nerve voluntary S 2,3,4
4. Sensory stretch receptors parasympathetic
NOCTURNAL ENURESIS :
Etiology:
Primary
1. Familial genetic predisposition
2. Deep sleep bladder distension either fails to cause central arousal or despite central arousal there is
no awakening or inhibition of micturition (Type 1 or Type II a nocturnal enuresis)
3. Disturbed circadian rhythm of ADH (Vasopressin) secretion low nocturnal secretion resulting in
higher nocturnal urine volumes. It is suggested that Vasopressin regulated water transport may be
effected through its influence on the expression of aquaporin AQP2 on the collecting duct (VP

62

4.
5.

6
7

increases AQP2). Aquaporins are proteins that mediate transmembrane water transport in a variety of
tissues including the kidney. ( Scand J Urol Nephrol Vol 31, 1997 suppl 183 page31 - ?32)
Small bladder capacity (normal = 30cc/year of age)
Structural urological abnormalities e.g.
Neurogenic bladder
Obstructive uropathy with overflow incontinence
Ectopic ureter
Incontinence here is usually diurnal as well as nocturnal
Mental retardation
Developmental delay in bladder training

Secondary Non organic more frequent than organic but must exclude organic first as potentially
serious implications if an underlying pathological organic cause is missed
Organic (1-2%)
1. Renal urinary tract infection (commonest cause of secondary organic enuresis)
- urinary concentrating defect e.g. chronic renal failure, nephrogenic diabetes insipidus
2. Endocrine Diabetes mellitus / Diabetes insipidus
3. Nocturnal epilepsy
4. Dysfunctional voiding - important contribution of constipation
Non organic (>90%)
Emotional / Psychological - Stress/ anxiety- examinations, new school or new sibling
History
1. Symptoms of UTI, developmental delay, polyuria, polydypsia, constipation.
1. Timing of enuresis (diurnal + nocturnal or nocturnal alone).
2. Identify emotions stress /social problems
3. Emotional disorders and encopresis
4. Age of toilet training and nocturnal continence in child and parents.
5. Parent and child reaction to problem
6. Punitive measures
7. Previously tried strategies
8. Drugs e.g. diuretics
Interview parent and child together and separately
DANGER SIGNS SUGGESTIVE OF ORGANIC PATHOLOGY
1. Diurnal and nocturnal incontinence suggests neurogenic bladder
2. Continuous dribbling of urine suggests neurogenic bladder or obstructive uropathy with overflow
3. Poor urinary stream in boys suggests obstructive uropathy
4. Dysuria pain or straining at micturition suggests obstructive uropathy, UTI
5. Passing urine frequently with pain, and in small volumes, offensive urine, gross haematuria UTI
6. Polydipsia and polyuria diabetes mellitus or insipidus
7. Abnormalities of the lower back sacral dimple or sacral tuft of hair- suggests spinal cord anomaly
8. Failure to thrive
Any child with any of the above features should be referred for medical evaluation immediately
A child, on the other hand, who has never been dry and has no danger signs, is most likely to have primary
nocturnal enuresis and the parent/ guardian may try preliminary measures before seeking medical attention.
Examination
Growth parameters, BP, hydration, abdominal examination renal masses, bladder, fecal masses, perineum
ectopic ureter / urethral orifices, anal tone, reflexes and power in the lower limbs, lumbo-sacral area for
dimples, sinuses. Observe the urinary stream.

63

Investigations
Urine sediment centrifuged - for rbc, casts, casts
- uncentrifuged - for bacteria.
Midstream urine culture and sensitivity
Urine disptix blood and protein, sugar
Random urine specific gravity (SG) > 1.012 rules out diabetes insipidus and chronic renal disease ( if
proteinuria absent.
Hb, Hb electrophoresis, urea, creatinine electrolytes, bicarbonate.
If urine SG 1.010 repeat on fasting sample
If SG < 1.005 evaluate for diabetes insipidus (Water deprivation test)
FURTHER INVESTIGATION ONLY IF ABNORMALITY DETECTED ON PHYSICAL
EXAMINATION OR SCREENING TESTS. Most cases of enuresis are nonorganic in etiology.
Continuous enuresis is always pathological and should be investigated.
If diurnal and nocturnal enuresis coexist, treat diurnal enuresis first
Treatment of nocturnal enuresis starts seriously at age 5 years or older
1. Treat organic lesion if present if absent , proceed to (2)
2. Counseling of child to identify stresses, allay anxieties; counsel parent to reward dry nights and cease
punishment
3. Behaviour modification colour in dry nights with crayon on standard calendar and bring to clinic (or
use sticker star chart)
4. Withhold fluids at least 2 hours before retiring to bed. Encourage increased daytime fluid intake to aid
bladder stretching
5. Child urinates twice in a row, just before going to sleep, and is awakened by the adult to pass urine one
hour before the predictable enuretic time. (Awaken only once per night)
6. Protect the mattress with a plastic cover and the sheet with a thick towel
7. Do not put the older child in plastic pants as this acts as another means of eroding self confidence
8. The child should help to wash urine out of his wet underwear should an accident occur
9.

Bladder exercises (Children > 6 years of age)

- Stream interruption exercises; delay micturition as long as possible and interrupt the stream for as
long as possible before completing the void.
Aim is to increase external sphincter tone and
awareness
- Bladder augmenting exercises: Bladder capacity is increased by augmenting diurnal fluid intake
while postponing micturition for as long as possible

10 Enuresis alarms designed to alert the child or parent when the child wets the bed during the night.
There are many variations in the design of the alarm, from the bulky bed pad and bell, to smaller
devices in the underwear to detect wetness with an alarm on the wrist or attached to the clothes, or
more recently an oscillator in the underwear that vibrates when the underwear becomes wet.
(Evaluation of nine different types of enuresis alarms Arc Dis Child 1984; 59:748-758). If nocturnal
enuresis occurs at a predictable hour, an alarm clock may be set to alarm 1 hour before the predicted
enuresis so the child may be awakened to urinate before enuresis occurs. Alarms should be continued
for 3 weeks after the last dry night and should be a supplement to the other measure (1) (6).
Results: slow but highest cure rate of all. 80% are dry within 4 months, most within 2 months of
treatment. 10% will relapse.
Mode of action to awaken child as urine is passed and cause the child to suppress further micturition
voluntarily - thus producing a conditioned response. Enuresis resolves by either nocturia or development
of hypersensitivity to bladder contraction resulting in inhibition of micturition reflex while asleep.
Some predictors of failure include:
Family stress
Failure to awaken in response to the alarm

64

 Abnormal behavioural symptoms

Lack of parental concern about the problem
Childs lack of distress about the enuresis
More that one wetting episode per night
(Scan J Urol Nephrol Vol 31, 1997, Suppl.183 page 55-58)
11 Drug therapy is a last resort and should only be used in combination with other measures where these
alone have failed. Not recommended for use in children under age 5 years.
Imipramine (Tofranil )
Dose: 10mg orally 1 hour before bedtime. Increase weekly to maximum of 2.5mg/kg/day
Maximum dose: 75mg/day (age 6-12 years)
100mg/day (adolescent)
Duration : initial 2 week trial . Taper to avoid relapse after discontinuation. Give dose on alternate nights
then every third night for 4-6 weeks
Indication : children > 6 years old
MOA anticholinergic, central action, increases functional bladder capacity
Overdose cardiac arrhythmia, diastolic hypertension, tachycardia, leukopoenia, hepatitis dermatitis,
insomnia
Desmopressin (DDAVP, Minirin )
Intranasal - 20 40ug titrated during a period of 4-6 weeks Initial dose 20 ug
Oral 200ug/day (maximum 400ug/day). Given hour before or 2 hours after meal as food reduces
absorption
If there was a positive response (substantial reduction in the number of wet nights or a decrease in the
degree of wetness as assessed by the parents) Desmopressin was extended to 3 months using the optimal
dose. If the therapy was still effective after 3 months, treatment was continued for additional 3-6 months
eventually tapering the dose (usually to 10ug, until complete dryness was achieved for a period of 3-6
months). (Scan J Urol Nephrol (1997) 31:Suppl 183, 33-35)
May be ineffective a) in children who do not have derangement of their ADH secretion b) if nose is stuffy
Side effects: dilutional hyponatremia or fluid overload if high fluid intake overnight.
Indications:
a) monosymptomatic nocturnal enuresis (exclusive night- time wetting)
b) b) children > age 5 years
DIURNAL ENURESIS and the NEUROGENIC BLADDER
Definition:
Daytime wetting beyond the age of 5 years the age at which reliable daytime dryness is expected to have
been achieved.
May be benign or pathological
Relatively benign types

are characterized by damp underwear only, and no straining

examples include
1. Urge incontinence though this may be a symptom of serious bladder dysfunction
2. Stress incontinence pubertal females, gymnasts on exertion Treatment: empty bladder before
exertion +/- sympathomimetics
3. Giggle incontinence sudden complete bladder emptying with giggling only normal urinalysis
and upper tracts. Treatment: anticholinergics +/- sympathomimetics
4. Transient wetting UTI, emotional stress, illness treat cause, reassure

65

5.

Post void dribbling improper wiping, inadequate shaking (urine trapped under foreskin), vesicovaginal reflux (in fat girls with thighs close together urine flows down the perineum to the vagina.
Treatment: void facing the toilet, wipe standing up after voiding.

Pathological forms:
Frequent voider uninhibited bladder contractions
Infrequent voider large bladder capacity, incomplete bladder emptying, recurrent UTI
General principles of evaluation of diurnal enuresis
History assess the severity and frequency of the problem (continuous or intermittent), general health,
social/emotional/ developmental history, constipation, encopresis, symptoms or urinary tract infection.
Dryness for extended periods e.g. at night suggests that there is no serious pathology. Ask about
voiding in a rush (leaving insufficient time for bladder emptying)
Examination general growth parameters, blood pressure, abdominal masses including faecal,
bladder and renal. Specific perineum for ectopic orifices, lower limb reflexes , spine for defects
Investigations screening as for nocturnal enuresis
- where pathology suspected MCUG, cystometrics, renal ultrasound +/- renal scan
INDICATIONS FOR NEPHROLOGY REFERRAL IN ENURESIS:
Infrequent voiders
Straining
Encopresis or chronic constipation
Continuous wetness
Combined diurnal and nocturnal enuresis
History or examination suggestive of underlying pathology
General management strategies for diurnal enuresis:
Keep chart divide day into 4 segments record and give praise for the dry segments
Bacteriostatic / fungicidal dusting powder to underwear to reduce the offensive odour
Bladder training infrequent voiders: void more frequently at least every 2 hours watch alarms
may be used as reminders
- for those who rush micturition: stay on the toilet long enough to void a second time 30
seconds after the first
Pathological diurnal enuresis
PATIENTS WITH NEUROGENIC BLADDERS WILL EITHER FIT THE PATTERN OF THE
INFREQUENT VOIDER (FLACCID NEUROGENIC BLADDER) OR THE FREQUENT VOIDER
(SPASTIC NEUROGENIC BLADDER) AND THE PRINCIPLES OF THEIR TREATMENT ARE
SIMILAR.
Frequent voider
Types persistent infantile bladder / detrusor hyper-reflexia
General features: Urgency, urge incontinence, frequency, staccato stream, squatting (holding postures),
recurrent UTI
Consequences: potential for bladder wall thickening and VUR
Investigations:
As for nocturnal enuresis
A) Persistent infantile bladder
Peak incidence 5 7 years
Uninhibited bladder contractions against a contracted external sphincter result in increased intravesical
pressure, bladder wall thickening, trabeculation and VUR in 33 -50%
Symptoms: urgency, urge incontinence, frequency, staccato voiding +/- nocturnal enuresis,
recurrent UTI, dysuria even after the treatment of UTI, holding postures e.g. Vincents curtsey

66

Ultrasound- small bladder with thickening of the bladder wall and trabeculation
MCUG -vesico-ureteric reflux (VUR), proximal urethral dilatation due to incomplete relaxation of
external sphincter during voiding
Urodynamics - detrusor hyperreflexia, reduced bladder capacity, detrusor / sphincter dyssynergia,
increased intravesical pressure, VUR, upper tract damage

B) Detrusor hyperreflexia
Child attempts to suppress uninhibited bladder contractions during bladder filling by voluntary
contraction of the external sphincter resulting in the characteristic posture
During bladder filling there may be periodic relaxation of the external sphincter without increase in
the detrusor pressure resulting in a sense of urgency or an episode of urge incontinence
Bladder emptying is usually complete because normal detrusor contraction and complete external
sphincter relaxation occur at full bladder capacity
US and MCUG are usually, but there may be mild bladder wall thickening and VUR may occur
Some children with diurnal enuresis and detrusor hyperreflexia may rarely be unresponsive to
anticholinergics and timed voiding. Some may have spina bifida occulta with associated neurological
abnormalities. Children with diurnal enuresis and spina bifida occulta should have neurological
consultation.
Treatment
Anticholinergics to inhibit bladder contractions
Oxybutynin (Ditropan)
Hyoscinamide hydrobromide (Levsin)
Probanthine (Propantheline)
Terolidine (new drug -very little pediatric experience)
Treatment and prophylaxis of UTI
Timed voiding

Tricyclic antidepressants are ineffective

Infrequent voider: a) Lazy bladder syndrome b) Hinman syndrome
Voids very 8 12 hours
Large capacity bladder
Incomplete bladder emptying
Recurrent UTI
Straining at micturition
Severe constipation and encopresis
A)

Lazy bladder syndrome

Symptoms of UTI, constipation, encopresis
Large hypotonic bladder
Reduced sense of bladder filling ultimately resulting in myogenic failure
Non obstructive, but because of detrusor hypotonicity straining is needed to empty bladder
U.S. +/- bladder thickening, mild upper tract dilatation
MCUG larger than normal capacity bladder which empties incompletely
Urodynamics: very large capacity bladder, highly compliant, either unsustained or absent detrusor
contractions, large post void residua, normal relaxation of the external sphincter.
Management bladder training, triple voiding, and last resort intermittent catheterization

B) Hinman syndrome (non neurogenic neurogenic bladder) (pseudoneurogenic bladder), detrusor

sphincter dyssynergia, silent subclinical or occult neurogenic bladder
Symptoms urgency, infrequent voiding, weak intermittent stream, severe constipation, diurnal /
nocturnal enuresis, recurrent UTI. Lack of appreciation of bladder filling
Detrusor / sphincter dyssynergia in neurologically intact children
Contraction of detrusor against a closed external sphincter results in functional bladder obstruction,

67

obstructive uropathy, VUR

US heavily trabeculated, large capacity , poorly compliant bladder, high post void residua, secondary
hydronephrosis, obstructive renal damage
MCUG: grossly trabeculated, large capacity bladder which empties incompletely, 50% have VUR.
During voiding there is narrowing of the urethra in the region of the external sphincter which fails to
relax and may even tighten, resulting in proximal urethral dilatation, increased intravesical pressure
and weak or intermittent urine stream. There may e seepage of urine despite vigorous contraction of
the external sphincter
Urodynamics: large capacity , poorly compliant bladder. Uninhibited bladder contractions
Management

Drugs : anticholinergics for bladder instability, adrenergic blockers (Prasosin

Minipres) to inhibit bladder neck contractions, Diazepam, Baclofen to inhibit striated muscle
hyperactivity

Bladder retraining and bladder drill (timed voiding every 2-3 hours)

Intensive correction of constipation enemas, increased dietary fiber and fluids,+/chronic use of fibre based laxatives

Hypnotherapy biofeedback, psychotherapy

intermittent catheterization if bladder emptying cannot be otherwise achieved

surgery for VUR is ineffective as the condition will recur

DIURNAL URINARY FREQUENCY IN CHILDREN

(Polakaluria, neurotic frequency of micturition in children)

Etiology unknown ? attention seeking ? reaction to stress

Sudden diurnal frequency and urgency
Rarely nocturnal enuresis
Duration : days to months
Normal examination, urinalysis and urine culture
Treatment :

Identify stress and counsel

Give more attention

Timed voiding - delay micturition

Indomethacin 1mg/kg/dose t.i.d. for 7 days (last resort)

Is a self limiting disorder

68

DRUG TREATMENTOF DIURNAL ENURESIS

DRUG

DOSE

Sympathomimetics
Ephedrine
Pseudoephedrine
Phenyl propanolamine
Local preparations:
Sudafed syrup:
Pseudephedrine HCL
60mg/tab, 30mg/5mls
syrup
Anticholinergics

0.5mg/kg b.i.d (max 1mg/kg

t.i.d)
0.4 mg/kg b.i.d (max 0.9mg/kg
t.i.d)
2.5 mg/kg b.i.d.(max 2.5mg/kg
t.i.d.)

Oxybutynin (Ditropan)

Starting dose 2.5 mg bid

Max 5mg t.i.d.

Hyoscyamine (Levsin)
Tablet 0.125mg
Elixir 0.125mg/5ml
Drops 0.125mg/ml

4 doses per day are usually

effective
<2years (max 6 doses /day)
wt 3.4kg 4 drops q4h
Wt 5kg - 5 drops q4h
Wt 7kg - 6 drops q4h
Wt 10kg - 8 drops q4h
Wt 15 kg 11 drops q4h
2 - < 12 years
10 kg tsp / tab q4h
20 kg tsp / tab q4h
40 kg tsp / tab q4h
50 kg 1 tsp /1 tab q4h
adults > 12 yrs 1-2 tsp / tab q4h

Probantheline
(Probanthin)

1mg/kg/day (given t.i.d)

MODE OF ACTION
adrenergic stimulant
Increased urethral resistance
Increased bladder storage

Giggle incontinence
Stress incontinence
Do not use if
hypertensive

Inhibit spasmodic detrusor

contractions
Inhibition of bladder cholinergic
innervation. S/E blurred vision,
dry mouth, hyperpyrexia

Giggle incontinence
Persistent infantile
bladder
Detrusor
hyperreflexia
Hinman syndrome
Age > 5 years

No age restriction

Age 1 month 12
years
Reduce bladder neck resistance,
Smooth muscle relaxants

Adrenergic blockers
Prazosin (Minipres)

0.05mg/kg b.i.d.
Max 0.1mg/kg t.i.d

Phenoxybenzamine

0.3mg/kg bid

INDICATION

For incomplete
bladder emptying

69

References:
1. Urolog Clin N Am(1995) 75-93 Wetting and functional voiding disorders. Rushton GH
2. Scan J Urol Nephrol (1997) 31:. Suppl 183
3. Pediatr Nephrol (1998) 2: 55-66 Management of the neuropathic bladder of childhood
4. Pediatric Nephrology (1999) 4th Edn. Barratt, Avner, Harmon eds. Lippincott, Williams and Wilkins
pub, page 928

70

CHAPTER 10
ACUTE RENAL FAILURE
Acute renal failure - Definition
Acute renal dysfunction resulting in azotaemia and disorders of water, electrolyte and acid base
homeostasis.
Definition of oliguria varies with age
Age
Neonate
Infant
Child

Urine output
< 1 -0.5cc/kg/hr
< 0.6 - 0.8cc/kg/hr (< 15 20 cc/kg/day)
< 0.4 0.6 cc/kg/hr (< 10 15 cc/kg/day)

Anuria
Urine output less than 1cc/kg/day or no urine passed in the first 48 hours of life.
Aetiology:
Bilateral urinary tract obstruction
Bilateral renal vein thrombosis
Bilateral cortical necrosis
Severe glomerulonephritis
Classification:
Pre-renal renal hypoperfusion e.g. dehydration, shock
Renal renal parenchymal disease eg. acute glomerulonephritis, tumour lysis syndrome
Post renal bilateral obstruction eg. posterior urethral valves
Differentiation of types of acute renal failure
Renal (intrinsic)
Volume overload

Clinical

Pre-renal
Dehydration
Shock

Post renal
Palpable bladder or
kidneys

Fluid challenge

+ ve

- ve (dangerous)

- ve

Urine / plasma osmolality

> 1.5:1

1:1

variable

Urine specific gravity (USG)*

>1.018
>1.015 (neonate)

1.010 1.015

variable

Urine Na (UNa) mmol/l

<10

>25

variable

Blood urea (mmol/l)

x 2.8.
Serum creatinine (mol/l)x .01

>10:1**

<10:1

>10:1

Microscopy

Hyaline and
granular casts

RBC, tubular cells, RBC

haem / granular casts

Normal or WBC /
bacteria (UTI)

71

Differentiation of types of acute renal failure ctd.

Pre - renal

Renal (Intrinsic)

Post renal

Urine: dipstix

Negative

Positive blood / protein

Negative

Renal ultrasound

Normal

No obstruction

Obstruction

Treatment
Rehydrate
Diagnosis dependent
Relief of obstruction
* These values are unhelpful if diuretics are used. Specific gravity may be falsely increased by proteinuria,
glycosuria, mannitol and radio- opaque dyes
** Ratio falsely elevated by blood in GI tract
Therapeutic differentiation of pre-renal from intrinsic renal failure
Severe oliguria / anuria with signs of dehydration
CVP <5-8 mmHg
*

Fluid challenge
N/saline or fresh frozen plasma
(or Blood / albumin depending on clinical situation)
20cc/kg over 1-2 hours or less
repeated until hydration satisfactory
(CVP 10-12 mmHg)

significant response

oliguria persists

urine output >2cc/kg/hr

Diagnosis: pre renal failure

Try Furosemide 2-5mg /kg IV push

(dose depends on serum creatinine)
OR
Mannitol *0.5 1 g/kg IV over several minutes

Treatment : rehydrate
Oliguria
Persists
<2cc/kg/hr
Intrinsic renal failure

Diuresis
> 2cc/kg/hr
Pre-renal renal failure or
Converted oliguric to non
Oliguric renal failure

Note:
Mannitol* may increase blood volume and cause pulmonary oedema and is not recommended in
congestive heart failure. CVP monitoring of fluid challenge is ideal
Severe cardiac failure may cause acute renal failure and has the features of pre- renal failure.
The treatment for this type of ARF is improvement of cardiac output and relief of cardiac failure
NOT A FLUID CHALLENGE!!! Interpret ARF in the clinical setting in which it occurs!
Dopamine (0.5 5 g/kg/min may be used to potentially prevent ARF and improve renal perfusion
after hypoxic / ischaemic renal insults. Higher doses improve cardiac contractility but cause

72

vasoconstriction and may impair renal function further. (Ped Nephrology 5th edition 1999 pg1125,
Chapter 69- management of acute renal failure)
Furosemide in high doses may be ototoxic especially in the presence of metabolic acidosis.

Investigatons:
Hb, WBC, platelet count, urea, creatinine, electrolytes, bicarbonate, calcium, phosphate, albumin. Specific
investigations depend on the likely cause eg. glomerulonephritis. Urine (pre-diuretic) spot urine sodium,
specific gravity, microscopy (spun) for cells and casts. Unspun urine microscopy for bacteria, MSU for
culture, dipstix for blood and protein.
Management:
1.

Fluid restriction
Insensible losses (400ml/m2/day or 20-30 ml/ kg/day + output + extra fluid for fever (see Chapter 1)
- may give only insensible losses if very oedematous
- initially if NPO and oliguric, use D10 W only as no electrolytes are necessary and more calories
may be given by this method.
- replace losses as they occur with N/saline (gastric losses) , D5% 0.2Nsaline or D4.3% 0.2 Nsaline
(diarrhoeal losses). Additional Na bicarbonate may be needed in the replacement of diarrhoeal
losses. Use spot urine Na and K to determine Na and K content of urine replacement during the
diuretic phase of ARF. This test is unhelpful if patient has been given a diuretic.

2.

Diet and calories

400 kcal/m2/ day Intravenous D10 W or total parenteral nutrition (Vamin 1.5g/kg/day protein). The
severity of protein restriction (0.5 1.5 g/kg/day) is dependent on the level of blood urea, the
presence of uremia and the availability of dialysis. No added salt Na 2mEq /kg/day maximum
(1mEq/kg/day if hypertensive). No sodium IV until diuresing. Early dialysis will permit better
nutrition. Low K if hyperkalemic or normokalemic and oliguric. No K added to IV fluids while
oliguric, unless hypokalemia develops from extrarenal losses.
Phosphate restriction: 500 600mg /day (wt <20g) / 600 1000mg (wt > 20kg)

3.

Metabolic acidosis (HC03 < 15mEq/l, pH < 7.2) add NaHCO3 2 mEq/kg /day IV / po. .If > 4 mEq/kg
NaHCO3 /day required to correct acidosis, consider dialysis.

4.

Hyponatremia treatment: fluid restriction.

If Na < 130mEq/l and symptomatic (seizures) 6% NaCl (1mEq /cc) IV. 6 mEq Na Cl /kg increases
serum Na by 10mEq/l. Prepare for dialysis. 6% NaCl is prepared on request from pharmacy. Serum
Na should not rise by > 10mEq /l /hr.

5.

Hyperkalemia
K > 5.5mEq/l Kayexalate 1gm/kg (po /PR) every 1 2 hours if necessary in sorbitol or D50 W constipation
K > 7 mEq/l :
1) Correct acidosis (may cause tetany if hypocalcemic). For each 0.1 pH is reduced, the serum K
increases by 0.6mEq/l) Na HCO3 1mEq/kg IV over 10 30 min
2) Dextrose 0.5g/kg/hr till sugar 14mmol/l (250mg/dl) shifts K into cells. (Destrostix every
hour)
3) ECG changes tall peaked T waves, wide QRS, prolonged PR interval , flattened P and R
waves, ST depression and prolonged QT interval Rx 10% Calcium gluconate 0.5ml/kg over
3-5 minutes reverses ECG changes (used with (1) -(3) plus kayexalate.
4) Avoid insulin. If used, dose = 1 unit soluble insulin / 5g glucose given. (0.1U/kg IV over 30
min)
5) B agonists (albuterol / salbutamol 5-10 mg nebulizer (adult dose) stimulates cellular uptake
of K limited paediatric use (Ped Nephr 15th edtn 1999 page 1126)

73

All measures (1-5) for hyperkalemia must be combined with Kayexalate until either diuresis occurs or
dialysis is instituted, to remove K from body
6.

Hypocalcemia - < 2mmol/l. usually occurs when PO4 > 1.8 mmol/l. If symptomatic Rx 0.5cc/kg
10% calcium gluconate IV over 5 minutes preferable with ECG monitoring. Watch for
bradycardia. Maintain with 120cc/m2/day of 10% calcium gluconate (See also Chapter 1 for
calcium correction in hypoalbuminemia, and Chapter 7)

6) Hyperphosphatemia reduce dietary PO4, phosphate binders calcium carbonate 220-500mg/kg/day po

7) Seizures

Rx hypoglycemia : IV 0.5cc/kg D50W diluted in equal volume of water for injection, then
maintain on D10w IV
Rx s hypertensive crisis (see Chapter13 )
Rx electrolyte, calcium imbalance
Diazepen, Dilantin, phenobarbitone
Prepare for dialysis

8) Hypertension (see Chapter 13)

Monitor
BP , pulse, RR frequently
Daiy weights, accurate intake and output
Urine electrolytes Na and K aid in determining replacement fluid (pre diuretic)
Electrolytes, calcium phosphate, urea, creatinine, (+/- glucose) at least daily
NOTE:
Once urine output in the diuretic phase has been constant on regime of insensible losses and output,
gradually reduce intake and allow urine concentration to occur
On dialysis:
Allow sufficient fluid intake to cover dialysis losses and give adequate calories, while
ensuring net fluid removal if still fluid overloaded
Monitor blood glucose hyperglycemia may occur
Daily peritoneal fluid samples for gram stain cell count and culture to detect peritonitis early
Dialysis losses may be adjusted to enable sufficient fluids for adequate caloric intake to be
given
Tumour lysis syndrome:
Noted in patients with high tumour loads or B cell neoplasms.
Associated with elevated serum uric acid and serum phosphate, hyperkalemia and hypocalcemia
Uric acid deposition in the tubules results in intrinsic renal failure
Rx: alkalinization of the urine (pH > 7), Xanthine oxidase inhibitors (eg Allopurinol), slow
introduction of chemotherapy. Some patients may need dialysis.
Ref. Pediatric Nephrology (1999) 13: 153-162.Renal involvement in children with malignancies

74

Drug dose adjustments for children in renal failure

Use of the table:
1) Determine your patients actual DFR in ml/min/1.73m2 as follows:
GFR (ml/min/1.73m2 = Ht (cm )
x
K
Serum creatinine (mol/l) X 0.01
K= 0.55 (age 2-12 years)
= 0.33 (low birth weight infants <1 year)
= 0.45 (full term infants < 1 year)
2) Convert GFR (ml/min) on table to ml/in/1.73m2 as follows:
GFR ml/min/1.73m2 = GFR ml/min
x 1.73
BSA (m2)
BSA = your patients body surface area
3) Compare GFR ml/min/1.73 m2 on Table (2) with your patients actual GFR and determine into which
category your patient falls
eg. a child has a GFR calculated as in (1) of 60ml/min/1.73m2. Her BSA is 1m2.
Therefore, from Table, GFR of 50ml/min = 50 x 1.73 = 86ml/min/1.73 m2
1
and a GFR of 10ml/min
= 10 x 1.73 = 17ml/min/1.73 m2
So for drug dose adjustment, she would fall into the category GFR 10 50 ml/min
Abbreviations: (R ) renal
(H) hepatic
(D)
dosage
(I )
interval
Adjustments may be made to either the dosage (D ) or dosing interval ( I ) or both (see
Method on Table). The numbers given for dosage are the % of normal daily dose, and
interval, represents the hours between doses.

for

75

Drug adjustments:
Drug

Elimination
And
metabolism

Method of
adjustment

GFR
(mls/min)
>50

GFR
(mls/min)
10 - 50

GFR
(mls /min)
< 10

60-90

30-70

20-30

Every
12-18

Every
12

Every
24

Aminoglycosides
Amikacin

Gentamycin,
Kanamamycin
Tobramycin

D
I

60-90
8-12

30-70
12

20-30
24

Neomycin

No change

8-12

12-36

NR

24

24

24-36

Flucytosine

12-24

24-48

Ketoconazole
Antivirals
Acyclovir
Cephalosporins
Cefaclor

None

None

None

24

48

R (H)

100

50 -100

33

Comments

Ototoxic and nephrotoxic;

need usual loading dose
in renal failure. Need
to 2/3loading dose after
haemodialysis

Antifungals
Amphotericin B

Cefadroxil

Cefazolin

Nephrotoxic: renal
tubular acidosis;
hypokalaemia:
nephrogenic DI
Hepatic dysfunction :
Marrow suppression

12-24

24-48

Cephalosporins:
May be nephrotoxic in,
combination with
aminoglycoside
antibiotics,
diuretics and volume
depletion.. Rare

12-24

24-48

Cefotaxime

R (H)

6-8

8-12

12-24

allergic interstitial

Cefuroxime

6-8

8-12

12-24

nephritis Absorbed well

Cephalexin

6-8

12

from peritonea fluid in

CAPD; Transfer from

Cephalothin

R (H)

8-12

Ceftazidime

D
I

None
12

None
12

50
24

R/H

none

none

none

none

blood to peritoneum is
poor

Ceftriaxone

76

Drug

Elimination
And
metabolism

Meropenem

Method
Of
Adjustment
D/I

GFR
(mls/min)
-

Chloramphenicol

GFR
(mls/min)
(26-50 )
1 unit dose q
12 h
(10-25)
unit dose q
12h

GFR
(mls/min)
unit dose
q 24 h

H (R)

none

none

none

Clindamycin

none

none

none

Erythromycin

none

none

none

H (R )

12

24

Lincomycin

Comments
Give unit dose at end of
haemodialysis

Vestibular toxickty: GI
symptoms like uraemia
Metronidazole

H (R )
H (R )

I
D

8
100

8-12
avoid

12-24
avoid

NR (R )

100

avoid

avoid

Nalidixic acid
Nitrofuranoin

Interstitial nephritis,
seizures / coagulopathy

Penicillins:

R(H )

R(H )

Amoxil
Ampicillin

(> 30
ml/min)
8
6
(>
30ml/.min)

Augmentin

Metabolits accumulate
Met acidosis in overdose
Peripheral sensory
neuropathy: ineffective
when GFR <30ml/min

R(H)

(10-30ml/min)
12
(max 500mg
bd)

24
(max 500mg
od)

6-12

12-16

(10 30
ml/min)

I
12

24

none

none

R(H )

8
none

R(H)

6-8

8-12

12-16

H(R)

12

18

24

3mmol Na /g
In adults GFR 1030ml/mim0 1.2g IV load
then 600mg bd
GFR<10ml/min- 1.2gIV
load then 600mg od

Cloxacillin
K salt has
1.7mmol/million units

Penicillin G
Sulphonamides +
Trimethoprim (TMP)
TMP /
Sulphamethoxazole

Protein binding decreased

in uraemia

77

Elimination
And
metabolism

Method
Of
Adjustment

Trimethoprim

R(H )

Vancomycin

Drug

Drug

Elimination
and
metabolism

Method
of
adjustment

GFR
(mls/min)

GFR
(mls/min)

GFR
(mls/min)

8-12

12-24

24 -72

72 - 240

240

GFR
mls/min
> 50

GFR
mls/min
10- 50

GFR
mls /min
< 10

4
4

6
4-6

8
Avoid

Comments

Comments

Analagesics
Paracetamol

H
H (R)

I
I

Acetyl salicylic acid

(Aspirin)

Opiates:
Codeine, morphine,
naloxone, pentazocine

none

none

none

Benzodiazepines

none

none

none

Chloral hydrate

none

avoid

avoid

Phenothiazines Chlorpromazine

none

none

none

Nephrotoxic in overdoses
Nephrotoxic in
overdoses; may decrease
GFR when RBF is
prostaglandin dependent;
excretion enhanced in
alkaline urine; may add to
uraemic gastrointestinal
and haematological
symptoms
All these may cause
excessive sedation and
respiratory depression
Almay cause excessive
sedation and
encephalopathy in
patients with ESRD
May cause excessive
sedation

BP is best guide to dose

and interval

Antihypertensives
Prazosin

H (R )

none

none

none

Atenolol

none

50

25

Metoprolol

none

none

none

Propranolol

none

none

none

Significant accumulation
in ESRD
Hypotensive effect may
last 24 hours

78

Drug

Labetalol

Drug

Captopril

Elimination
and
metabolism

Method
Of
Adjustment

Elimination
and
metabolism

Method

GFR
(mls/min)

none

none

none

GFR

GFR

GFR

mls/min
> 50

mls /min
10 -50

mls/min
< 10

none
(< 30 > 10)
D 2.5 5 mg

25
(< 10)
mg (dialysis
days)

(GFR 50 20
ml/min/1.73m2
)
1.25mg-5mg
24

GFR < 20ml

/min/1.73m2 )

Enalapril

I or D

Rimipril

none

Hydrallazine
Minoxidil
Nitroprusside

R (H)

GFR
(mls/min)

none
(<80 >30)
D 5 10 mg

Diazoxide

R(H )

GFR
(mls/min)

Adult guidelines only

avoid

D
I

none
8

none
8

none
8-16
12-24

none

none

none

NR

none

none

none

H (NR )

Comments

Non renal excreted-no

dose adjustment needed

Calcium blockers
D

none

none

None

D
I

100
24

25-75
36

10-25
48

R (H)

none

none

none

R
R

6-12
none

12-24
none

avoid
avoid

Nifedipine
Digoxin
Diuretics
Furosemide
Spironolactone

ototoxic
Ineffective when GFR <
30ml/min

Thiazides

79

Drug

Elimination
And
metabolism

Method
Of
Adjustment

GFR
(mls/min)

GFR
(mls/min)

GFR
(mls/min)

May potentiate uraemic

bleeding

Anticoagulants
NR
H

D
D

none
none

none
none

none
None

H ( R)
H

D
D

none
none

none
none

none
none

H
Elimination
And
metabolism

D
Method

none
GFR
ml/min
>50

none
GFR
Ml/min
10 - 50

none
GFR
Ml/min
<10

D
I

none
8

75
8-12

50
12 - 24

H(R <15%)

none

none

none

Azathioprine

none
24

none
24

none
36

Cis platinum

none

75

50

Cyclophosphamide

D
I

None
12

None
12

Doxorubicin

H (R )

none

none

75

Methotrexate

none

50

avoid

Mithramycin

none

75

50

Mitomycin C

none

75

50

Vinblastine

none

none

none

Vincristine

none

none

none

Corticosteroids

none

none

none

Cimetidine

100
6

75
8

50
12

Heparin
Warfarin
Anticonvulsants
Phenytoin
Sodium valproate
Carbemazepine
Drug

Comments

Interstitial nephritis.
Possible SIADH
Comments

Anti-inflammatory
drugs
Allopurinol

Indomethacin
Antineoplastic agents

D
I

Allopurinol increases
drug effect
Nephrotoxic.

50-75
18-24
Acute renal failure and
nephrotic syndrome
Nephrotoxicity prevented
by urinary alkalination,
forced diuresis
Nephrotoxicity, acute
renal failure, decreased
Ca++, K+, PO4Nephrotoxicity

May aggravate azotaemia,

Na retention

80

References re Drug doses:

1. Paediatric Nephrology (1997) 1: 183 194 (for drug dose adjustments)
2. Package inserts of various drugs

Bleeding in Uraemia
Etiology:
1.
2.
3.
4.
5.

Inhibition of platelet function by uraemic toxins

Reduced function of Von Willebrandts Factor (vWF)
Increased nitric oxide (NO) production resulting in platelet dysfunction. Blocking nitrous oxide
production in uremic anaemia corrects bleeding time
Increased half life of heparin in uremic patients may result in prolongation of PTT after dialysis
Anaemia may increase the risk of bleeding:
In anaemia, the blood flow is less turbulent, and the platelets have less chance to interact with the
damaged vasculature
RBCs contain enzymes which augment platelet function

Assessment of platelet function: - clinical:

1.
2.

3.

Platelet number
Bleeding time vs platelet closure time:
The bleeding time in some patients bears no relationship to the platelet count.
The bleeding time is not a specific indicator of platelet function
The bleeding time is a poor indicator of surgical risk
The platelet closure time is sensitive to platelet adherence and aggregation abnormalities and therefore
has increased sensitivity for vWF screening compared to the bleeding time.

Treatment of acute uraemic bleeding:

1. DDAVP or
2. Cryoprecipitate or
3. Estrogens
4. Vascular factor
5. Nitric oxide synthesis inhibitors
6. Epogen / blood transfusions
7. Dialysis
8. Adjunctive treatment transfuse to PCV of 30% (to overcome negative effect of anaemia) +/- platelet
transfusion
Drugs:
Cryoprecipitate: (Cryoprecipitate contains Factor VII, vWF, fibrinogen and factor III, and virtually all
plasma components.

Mode of action in uremic bleeding unknown

Reduces bleeding time for 1 18 hours
It will not reduce the bleeding time in all patients
Dose 2 units / 10 kg will increase the fibrinogen level 100mg/dl except in DIC
Usual dose given is 10 units IV q 12 hours (adult)
Used in uremia if patient unresponsive to other modalities eg dialysis , DDAVP or oestrogen
Risk transmission of blood borne diseases

DDAVP:

81

Mode of action
Stimulates vWF release from the endothelial cells
Improves ATP release
Increases serotonin uptake
Increases serotonin uptake
Increases catecholamine release
DDAVP Dose:
0.3ug /kg IV or subcutaneously. IV dose given in 100 cc Normal saline over 45 minutes
3.0umg /kg intranasally
onset of effect in 1 hour
duration 4 24 hours
Tachyphylaxis begins at 24 48 hours
Indications
For short term prevention of uremic bleeding
Dialysis
Partly corrects bleeding time
Increases protein C

-- Causes slight increase in vWF

References for cryoprecipitate

Guidelines for the administration of cryoprecipitate The Wadsworth Center- New York State
Department New York State Council on Blood Transfusion Services January 1995 Revised
January 1996)

82

CHAPTER 11
ACUTE PERITONEAL DIALYSIS
Indications in acute renal failure
Absolute:
1) Severe fluid overload with CCF
2) Severe hyperkalemia unresponsive to medical Rx or with ECG changes
3) Severe hyponeatrmia
4) Server metabloic acidosis requiring > 2 doses of NaHCO3 (2mEq/kg/dose)
5) Uraemia
6) Fluid restriction curtailling ample nutrition
Relative:
1) Anuria
2) High urea and creatinine values alone are not indications
METHOD
Materials:
1)
2)
3)
4)
5)
6)

Pertioneal dialysis tubing, trocar and cannula

Yellow intracath #14 gauge needle 12 24 inches long
Cut sown set with narrow blade
2/0 silk on a straight needle
peritoneal dialysis fluid 1.5% dianeal (warm the fluid by placing in container of warm water
Lignocaine, Iodine, alcohol, mask and sterile gloves

Method:
1)
2)
3)
4)
5)
6)
7)

A
Consent form to be signed
Cross match 1 unit blood
Check PT, PTT platelets beforehand
Insert urethral catheter to empty bladder
Cleanse abdomen with Iodine and alcohol
Set up dialysis bags and attach to tubing (fluid should be tepid not hot and not cold)
Determine, before dialysis starts, the volume to be run in and mark out on bag (See Figure 1).
The markings are not exactly in the same position on all bags, so this method is only an
approximation. If more accurate measurement is needed, a Biuretrol must be attached to the
dialysis bag
8) Fill tubing with fluid
9) If the abdomen is not tense with ascites, by infusing dialysis fluid until adequate tension is
present one reduces the risk of damaging internal structures eg aorta, inferior vena cava and
bowel. Proceed to step B
10) If the abdomen is already tense with ascites, proceed to step C

83

Figure 1 Dialysis bags and volume markings

B
The procedure is as follows:
1) Remove guide wired from intracath
2) Set up tubing to dialysis fluid
3) Local anaesthetic to skin superficial and deep at area of proposed intracath insertion
Direct the needle of the intracath downwards gently but firmly
When you feel the pop thread the tubing and withdraw the needle around it
Push tubing in as far as it will go do not press deeply with the needle
4) Run in 30-50 cc/kg of dialysis fluid sufficient to make abdomen tense
5) Withdraw intracath
6) Proceed to insertion of peritoneal dialysis catheter

C
Insertion of the peritoneal dialysis cannula:
1) Site of catheter approximately 2 -3 cm inferior to the umbilicus and in the midline
2) Make a small incision at this point with the pointed end of the blade to include skin and subcutaneous
tissues just big enough for catheter

84

3) Hold peritoneal dialysis catheter with pointed trocar inside. Hand on top of catheter pushing
downwards firmly
4) When you feel the catheter enter the peritoneal cavity (a pop), remove the trocar (pointed internal
metal rod) and thread cannula (plastic part around the trocar) into peritoneal cavity quickly aiming the
cannula to the right or left iliac fossa (R preferably). Push in as far as it will go
5) Connect cannula (dialysis catheter ) to elbow and thus the remainder of tubing (already primed with
fluid)
6) Run out fluid from cavity into tubing should run as a steady stream
7) Pour in expected exchange volume
a) 40-60cc/kg infants and small children
b) 30-40cc/kg older children
Limiting factors abdominal discomfort, peritoneal leaks
8) If fluid runs in and out quickly after 3 rapid exchanges without dwells put purse string suture
around cannula tie tightly, fasten securely at the level of the skin then tie 3-4 knots up the side of the
catheter with the same uncut suture
DIALYSIS
Cycles: Usually best clearance with 30 minute cycles :
In over 5 minutes
Dwell over 20 minutes
Drain over 5 minutes
Tepid fluid
Clearance: Urea > K > Cl > Na > Cr > PO4 > uric acid > HCO3 > Ca > Mg
Dianeal composition: Na 132 K 0 Ca 3.25 Mg 1.3 Cl 101.75 Lactate 35 mmol/l
Rate of water removal (assuming adequate drainage) depends on [glucose] in dialysis fluid

1.5% dianeal (1.5% glucose) usually adequate, but may increase to 2.5% or 4.25% if inadequat fluid
removal. If there is no pre-mixed 2.5 % or 4.25% dianeal, they can be prepared as follows
to make 2.5% from 1.5% - add 40cc of D 50 W / 2 liters of fluid of 1.5% dianeal
to make 4.25% from 1.5% - remove 110 cc fluid from 2 litre bag of 1.55 dianeal. Add 110 cc of
D50W to bag

ADDITIVES
1) KCl 6 mEq / 2 liters added when serum K <4.0mEq/l
- may be increased in increments of 2-4 mEq/2l bag depending on serum K
2) No antibiotics prophylatically
3) Heparin 1000 units /2 litres of dialysis fluid in all bags to minimize formation of fibrin strands

PERITONITIS
Initial broad spectrum cover for peritonitis.

85

Empiric therapies:
Intraperitoneal
1) Cloxacillin 200mg/ 2litres + Gentamycin 10 mg /2 litres (regime used at UHWI with success despite
potential for inactivation when aminoglycosides mixed with penicillins) Staph is commonest
pathogen for peritonitis here
2) Cefotaxime - 500mg/2 litres
Adjust when sensitivities available
Loading dose of antibiotics in treatment of peritonitis:
First Line Drugs
Cloxacillin
Gentamycin
Cefalothin / Cefotaxime
Tobramycin / Gentamycin

Loading Dose (per 2litres dialysate)

no loading
16 mg/2l
Cefalothin 500mg cefotaxime1g
16mg Tobramycin and Gentamycin

Second Line Drugs

Loading dose (per 2 litres dialysate)

Ampicillin
Amoxicillin
Ticarcillin
Trimethoprim/sufamethoxazole
Clindamycin
Amikacin
Penicillin
Vancomycin
Amphotericin B
Cefuroxime
Ceftazidime
Fluconazole
Flucytosinnne

no loading
500 1 g
2g
640 mg /3200 mg
600mg
50 mg
2MU
1gm/2l
1mg /kg IV
400 mg
500 mg
no load
50 mg /kg IV/ po (max dose 2.0gm)

Recommended maintenance doses of intraperitoneal antibiotics for treatment of peritonitis (per 2litres)
Penicillin
100,000 U
Ampicillin
250mg
Amoxicillin
100 mg
Cloxacillin
250 mg
Ticarcillin
200 mg
Cephalothin / Cefotaxime
Cephalothin 250 mg / Cefotaxime 500 mg
Ceftazidime
250 mg
Cefuroxime
250 mg
Vancomycin
60 mg
Tobramycin
8 mg
Amikacin
24 mg
Gentamycin
8 mg
Clindamycin
300 mg
Trimethoprim / sulphamethoxazole
160 / 800
5 Fluruocytosine
Flucytosine 25 37.5 mg /kg po q 24 hr (max 1g)
Amphotericin B
1mg /kg/day IV
Fluconazole
3- 6 mg /kg IP / IV or PO q 24 48 hours (max dose 200mg)*
Rifampin
20 mg / kg /day po (max 600mg /day)
Taken from Consensus guidelines for the treatment of peritonitis in pediatric patients receiving
peritoneal dialysis Peritoneal Dialysis International Vol. 20: 610 624

86

PRECAUTIONS
Daily peritoneal fluid: c/s, gram stain, cell count. > 100 WBC / ml and > 50% neutrophils suggests
peritonits. start Rx as soon as sample taken for culture. Fluid is aspirated from the porthole (rubber
bung in tube in the dialysis line near patient entry) with a 25 gauge needle attached to a sterile syringe.
Clean the porthole with Iodine and wrap with Iodine soaked gauze for 10 minutes prior to inserting the
needle, in order to avoid iatrogenic peritonitis.*
Nurse is asked to call if problems arise (see below)
PROBLEM

Dialysis fluid running slowly out or fluid

retained on > consecutive cycles

SOLUTION

change patients position

change catheter position
Flush with heparinized saline 1000 units / 10
cc N / saline at porthole nearest Catheter entry
(use 25gauge needle and clean the porthole as
above prior to needle insertion*.)
Run fluid in no dwell, then out
Increase the drain time
Change the catheter

Dialysis fluid running in slowly

Flush catheter as above

Bloody dialysate or fluid leaking around the

catheter

Put 2nd tighter row of purse string sutures around the

catheter + ensure that heparin 1000u /2 litres has
been added to the bag (should be added from the
initiation of dialysis normally)

Dialysis fluid cloudy

Abdominal pain

Peritonitis fluid for cell count, gram stain and

culture
Start empirical antibiotics (Clox and Gent)
see peritonitis adjust when culture and
sensitivities available
Dialysis fluid too hot drain and replace with
TEPID SOLUTION
Change catheter position

Fever

Screen for infection

Too much fluid being removed per exchange

Inadequate fluid being removed per exchange

Increase glucose content of dialysis fluid

1.5% / 2.5 % / 4.25 % (see C)

Reduce glucose concentration of dialysis fluid

Replace excess losses IV / po

Change PD catheter if unable to get good drainage or inflow despite the above measures. Always flush the
tubing with about 20 50 cc of fluid as catheter is being withdrawn to minimize possibility of omentum
coming up in the catheter as it is being removed. Discontinue dialysis when urine output has improved
sufficiently that the original indications for dialysis are unlikely to recur off dialysis (not just when the lab
results are normal on dialysis).

87

References:
1) ISPD guidelines / recommendations. Consensus guidelines for the treatment of peritonitis in pediatric
patients receiving peritoneal dialysis. Warady, Schaefer et al. Peritoneal Dialysis International 2000.
20:610 624.
2) Paediatric Nephrology (1997) 1: 183 194 (for drug dose adjustments)
3) Pediatric Nephrology 15th Edition (1999) Barratt and Vernier Chapter 69 (1125 1126)

88

CHAPTER 12
CHRONIC RENAL FAILURE (CRF)
Definitions:
Renal impairment: glomerular filtration rate (GFR) 50-80% of normal for age*
Chronic renal insufficiency: GFR 50 -25% of normal for age* - growth failure, impaired calcium
absorption, abnormalities in plasma constituents
Chronic renal failure: GFR < 25% of normal for age* for at least 3 months- associated with
osteodystrophy, anaemia, hypertension and sometimes uraemia
End stage renal failure (ESRF): GFR <5% of normal for age*- insufficient to support life without
renal replacement therapy- symptoms: lethargy, somnolence, anorexia, nausea, vomiting, coma and
eventually death
*For age related normal values see Assessment of Renal Function
Aetiology
Congenital - e.g. Dysplasia, polycystic kidneys, obstructive uropathy, reflux nephropathy
Acquired - e.g. glomerulonephritis, tubulointerstitial disease, vascular pathology, chronic acquired
obstructive uropathy, tumours
Investigations
1. Blood urea, creatinine, electrolytes, serum albumin, Hb, reticulocytes, film, Hb electrophoresis, serum
ferritin or serum iron and TIBC (measure iron stores)
2. Serum calcium (reduced), phosphate (increased), alkaline phosphatase (increased) - osteodystrophy
3. Serum bicarbonate (reduced), serum uric acid (increased)
4. +/- fasting cholesterol and triglycerides
5. Spot urine: protein, phosphate and creatinine, sodium (for salt wasters)
6. Estimate GFR using Schwartz formula (see Assessment of Renal Function)
7. Estimate degree of proteinuria by spot urine (see Assessment of Renal Function)
8. 24 hour urine or timed urine to quantitate 24 hour urine volume
9. Calculate tubular reabsorption of phosphate (TRP) as index of PTH activity (or measure PTH levels).
Ideal sample: fasting urine phosphate and creatinine with fasting serum phosphate and creatinine
TRP = 1- [urine/ plasma phosphate**] X 100%
[urine / plasma creatinine***]
** units mmol/l ***units umol/l
Normal > 80%

Hyperparathyroidism <80%

10. Radiology
Renal ultrasound (renal lengths) and appearance - kidneys <2SD below mean for age suggest
chronic rather than acute renal disease
Renal glucoheptonate scan for scarring, perfusion and function - if reflux nephropathy / chronic
pyelonephritis thought to be the cause
DTPA renal scan for perfusion and function. In other centres a GFR scan can be obtained from
this study. The machine at UHWI cannot perform GFR scans on children < 18 years of age
For renal osteodystrophy (Renal osteodystrophy series) - non dominant hand
a) L wrist - bone age and evidence of metaphyseal rachitic changes
b) L hand - penetrated view - for subperiosteal resorption of terminal
phalanges in hyperparathyroidism
Micturating cystogram for vesico-ureteric reflux and outflow obstruction - lower tract
visualization is eventually needed in all children being considered for transplantation - may have
to be performed early in the case of children with suspected obstructive uropathy / reflux
nephropathy vs later in those with glomerular disease

CXR / ECG if hypertensive

89

11. Renal biopsy - Contraindicated if kidneys shrunken - i.e.

haemorrhage and histology unlikely to be helpful

end stage kidneys - high risk of

Monitoring
1.
2.
3.

4.
5.
6.
7.

Growth parameters, BP, urinalysis - each visit

Frequent urine cultures in children whose pathology is obstructive uropathy / reflux nephropathy
especially those with neurogenic bladders on intermittent catheterization. (See Urinary Tract Infection)
Blood:
Hb, urea, creatinine, electrolytes, serum proteins, calcium, phosphate and alkaline phosphatase - at
least every 3 months - correct the derangements observed eg metabolic acidosis and hyperkalemia.
Iron studies as indicated
Fasting cholesterol and triglyceride once per year
Urine: spot urine phosphate and creatinine - monitor TRP to follow adequacy of osteodystrophy
therapy (at least every 3 months)
Estimate GFR regularly using Schwartz formula, plot 1/serum creatinine vs time to assess the
progression of renal failure, and predict the time of end stage disease
Renal osteodystrophy series every 6 months once TRP is normal - bone age yearly
Remember to check tables for drug dosage adjustments for renal failure especially when
prescribing antibiotics

Management
Diet
1. Protein :
restricted to RDA+ (recommended dietary allowance) only when GRF < 50% of normal for
age
should contain essential amino acids and proteins of high biological value
2. Calories:
100% of the RDA for height age
weight for height is reduced or if there is other evidence of malnutrition, increase calories to
120% of RDA +
75% carbohydrate 20% fat and 5% protein (concern re diets high in fat because
hyperlipidemia common in CRF, and also high carbohydrate diets which may contribute to
hyperinsulinemia and subsequent hypertriglyceridemia)
infants may use supplements of polyunsaturated corn oil or medium chain triglycerides (MCT
oil)
3. Phosphate:
Limited to the RDA+
Aim to keep serum phosphate level normal for age (see Assessment of Renal Function)
Phosphate binders should be given immediately after mealtime to enhance dietary phosphate
binding
Calcium carbonate and acetate are the preferred phosphate binders
Aluminum containing phosphate binders are not recommended, but for patients who cannot
afford to by the calcium products they may have to be used- risk of Al toxicity - osteomalacia,
microcytic anaemia, encephalopathy
4. Sodium:
Restricted to 1mEq/kg/day if oedematous or hypertensive
Otherwise 2mEq/kg/day.
Small infants and older children with tubular disease may waste sodium and may demonstrate
poor weight gain until salt supplementation of 2 - 15 mEq/kg/day is added
5.

Potassium:
Restriction is usually necessary when GFR <5 ml/min/1.73m2 (end stage disease)

90


6.

In potassium wasting tubular disorders additional K may be needed

Fluids:
In CRF of glomerular aetiology, fluid restriction is usually needed early in the illness
In CRF of tubular aetiology, polyuria is usual, and high fluid intakes are needed to prevent
pre- renal failure. However in end stage renal failure from whatever cause, fluid excretion is
impaired and fluid restriction will be needed. Urine volumes in the polyuric patients need to
be measured periodically

Recommended Dietary Allowances+

Adapted from National Academy of Sciences. Recommended dietary Allowances.
10th ed. Washington, DC: National Academy press, 1989
Age

Midpoint
Height

Weight

Energy

Energy

Protein

Protein

Calcium

Phosphate

(yr)

(cm)

(kg)

Kcal/kg

Total
(rounded)

g/kg

Total

(mg)

(mg)

0-0.5

60

108

650

2.2

13

400

300

0.05 -1.0

71

98

850

1.6

14

600

500

1-3

90

13

102

1300

1.2

16

800

800

4-6

112

20

90

1800

1.2

24

800

800

7-10

132

28

70

2000

1.1

31

800

800

11-14M

157

45

55

2500

1.0

45

1200

1200

11-14F

157

46

47

2200

1.0

46

1200

1200

15-18M

176

66

45

3000

0.9

59

1200

1200

15-18F

163

55

38

2200

0.8

44

1200

1200

19-24M

177

72

40

2900

0.8

58

1200

1200

19-24F

164

58

36

2200

0.8

46

1200

1200

Drug therapy
1.

Prevention and treatment of bone disease:

Correct hyperphosphatemia, then start Vitamin D therapy. Vitamin D therapy should be started
once GFR < 50% of normal for age (<50mls/min/1.73m2).
Monitor serum calcium, phosphate and alkaline phosphatase, TRP and growth. Effective therapy
results in normalizing of serum calcium phosphate and alkaline phosphatase and improvement in
growth.

91

2.
3.
4.
5.

7.
8.

Avoid aluminum containing phosphate binders.

Do not use these preparations with citrate
containing medications and citrus fruits as they enhance aluminum absorption.
Calcium carbonate is currently the preferred phosphate binder
Aim to keep Ca / PO4 product <5.64mmol/l

Correction of metabolic acidosis - maintain serum bicarbonate -minimum of 20mmol/l

Prevention of folate, vitamin and mineral deficiency
Treatment of hypertension
Treatment of anaemia:
Erythropoietin (r-HuEPO- recombinant human erythropoietin) - Eprex
May be given SC (subcutaneously)- usual route, IV (intravenously)- hemodialysis patients, or
intraperitoneally (IP) - patients on peritoneal dialysis
Dose 150 U/kg/week SC /IV
If given SC add Lignocaine as injections painful
Contraindications- uncontrolled hypertension, poorly controlled seizures (seizures within the
preceding 12 months), severe iron deficiency (transferrin saturation <5%), pregnancy,
uncontrolled hyperkalemia
Start iron supplements at initial dose of 3mg Fe2+ /kg/day orally if serum ferritin <100ng/ml
+/or transferrin saturation < 20%. Adjust dose until values normalize. Iron supplements
should not be given within 2 hours of a meal and not with phosphate binders as absorption is
enhanced by gastric acidity
Aim for target Hb 10-11g/l or at least 2SD below the mean for age, but
< mean Hb for age
Monitor weekly-Hb, PCV, Retics, electrolytes, every 2 weeks -serum Fe, TIBC, ferritin,
transferrin, monthly -urea, creatinine, CBC, physical examinations. Daily BP at start of
therapy
Complications - Hypertension, hyperkalemia, iron deficiency and seizures - withhold
medication if this occurs
Duration of treatment - till target Hb achieved. Dose increased if target Hb not achieved by 12
weeks and reduced when target achieved
Treatment of short stature - with rhGH (recombinant human growth hormone)- not locally available
Renal replacement therapy Dialysis -peritoneal - CAPD- continuous ambulatory peritoneal dialysis
CCPD - continuous cycling peritoneal dialysis
-hemodialysis
Renal transplantation

92

Vitamin D preparations used in CRF

Rocaltrol (calcitriol)
1,25-dihydroxyvitamin D3
Alphacalcidiol
1 hydroxyvitamin D3

0.015 -0.05ug/kg/day
(given bid)- usual maximum
0.9ug/day
1.0ug 3x /week nocte
reduce dose to 2 x or once per
week when PTH < 100ng/l or
TRP normal

GFR < 50% of

normal

Capsules 0.25ug and 0.5ug.

Peak effect in 3 days. t/2 <24
hours

"

Mixture or capsule

Dihydrotachysterol (hytacherol)

0.125 1.5mg od

"

Capsules 0.125mg
Peak effect 15 days
t/2 50 hours

Vitamin D2
(calciferol)

0.2 - 0.6mg/day

"

1.25mg /tablet - only if no

other Vit D available- peak
effect 30 days- t/2 20days

Other drugs used in CRF Drug

Calcium carbonate

Usual dose
20-220mg/kg/day -given
tid immediately after meals

Indication
hyperphosphatemia

Comment
Usual daily dose 5.1 +/-2.5g
Tums 500mg CaCO3/tab

Aluminum hydroxide

10-30mg/kg/day - given tid

immediately after meals
2-5mEq/kg/day given tid

hyperphosphatemia

Avoid if possible - toxic

Aludrox 375mg/tab No citrate

Sodium bicarbonate

1-2mg/day (od)

Serum bicarbonate
<20mEq/l
Avoid folate deficiency

1 tab od
5mls od

Prevention of B1, B2, B5,

B6 and biotin deficiency

NO vitamin A preparations
(eg Tropivite ) -risk of toxicity
(hypercalcemia)

Vitamin C

In multivit preparation

Prevention of deficiency

Do not use with Al hydroxide

FeSO4

2mg/Kg Fe2+ od

Prophylaxis of iron
deficiency

5mgFeSO4 = 1mg Fe2+

prescribe in terms of Fe2+content

Kayexalate
(Resonium A)

1-2g/kg/dose

Hyperkalemia

May cause constipation

Furosemide

2-5mg/kg/od

Hypertension oedema

May be ineffective

Antihypertensives

Depends on drug

Hypertension

Erythropoietin

150U/kg/week (SC)

Prevention / Rx of anaemia

Folic acid
B vitamins(Multivite) Orovite
Beminal liquid
Becoplex syrup

Folic acid tabs 5mg (2.5mg OK)

See text

93

References:
1. Pediatric Nephrology -4th Edition (1999) - Barratt, Avner, Harmon -Editors. Chapter 72, 1155-1182
Physiology and management
2. Pediatric Nephrology - 4th Edition (1999) - Barratt, Avner, Harmon- Editors. Chapter 74,1197-1230.
Endocrine and growth disturbances
3. Pediatric Nephrology - 4th Edition (1999) - Barratt, Avner, Harmon- Editors. Chapter 75, 1231 -1249.
Osteodystrophy
4. Pediatric Nephrology (1995) 9: 737 -741. Alphacalcidiol pulses normalize uremic hyperparathyroidism
prior to dialysis
5. Pediatric Nephrology (1999) 13: 143-147. Safety and efficacy of erythropoietin in children with
chronic renal failure
6. Pediatric Nephrology (1999) 13: 701-708. Phosphate binders for control of phosphate retention in
chronic renal failure
7. Role of nutrition in the care on children with renal insufficiency. Pediatr Clin N America (1982) 29:
973-990
8. Pediatric Nephrology- 2nd Edition (1987)- Holliday, Barratt, Vernier - Editors. Chapter 49, 773 -798
Progressive loss of renal function.

94

CHAPTER 13
HYPERTENSION
Normal Blood pressure:
Systolic and diastolic pressures < 90th percentile for age and sex.
High normal blood pressure:
Average systolic and / or diastolic pressure 90-95th percentile for age and sex
Hypertension:
Average systolic and / or diastolic pressures > 95th percentile for age and sex on at least 3 separate
readings.
Significant hypertension:
Blood pressure 95 99th percentile for age and sex
Severe hypertension:
Blood pressure > 99th percentile for age and sex.
Blood pressure normals in children:
Premature neonate- See Figures 1-3 (J Perinatology 15: 470 479)
Age 1 12 months See Second Task Force on blood pressure control in children 1987 (Figure 4)
(diastolic BP is Korotkoff 4)
Age 1-18 years See 1996 Update on the 1987 Task Force Report (Figure 5) (diastolic BP is
Korotkoff 5)
Measurement:
The largest size cuff that can fit between the axilla and the elbow flexure, with the bladder completely
encircling the arm. Too small a cuff gives a falsely high reading.
According to the 1996 Task Force update, the diastolic blood pressure is taken as the 5th Korotkoff
sound i.e. the disappearance of the sound and no longer the 4th (muffling). In patients in whom the
5th Korotkoff sound is not heard, the diastolic is not recorded. Diastolic readings from the 1996 Task
force are based on K5, not K4 and therefore tend to be lower. In the 1996 Task for BP is related to
height and sex.

95

Figure 1

Figure 2

Linear regression of mean systolic and diatolic

blood pressures by birth weight on day 1 of
life, with 95% confidence limits (upper and
lower dashed lines)

Linear regression of mean systolic and

diatolic blood pressures by gestational age on
day 1 of life, with 95% confidence limits
(upper and lower dashed lines)

Figure 3
Reference for Figures 1-3: Zubrow et
al. J Perinatology (1995) 15:470-9

Linear regression of mean systolic and

diatolic blood pressures by post-conceptional
age in weeks, with 95% confidence limits
(upper and lower dashed lines)
96

Figure 4

Age-specific percentiles for blood pressure in boys (a) and girls (b) from birth to 12 months of age.
From the Report of the Second Task Force on Blood Pressure control in children 1987. Pediatrics
(1987) 79:5-6.

97


Figure 5

From the Update on the 1987 Task Force Report on High Blood Pressure in children and
adolescents. Pediatrics (1996) 98:653.

98

Aetiology of persistent hypertension:

Secondary:
Renal (31 78%) chronic renal failure, renovascular, renal parenchymal, renal tumours, obstructive
uropathy
Cardiac (8-15%) coarctation of the aorta
Endocrine (6-9%)
catecholamine excess phaechromocytoma, neuroblastoma
corticosteroid excess Congenital adrenal hyperplasia (11 and 17 hydroxlase deficiency)
thyrotoxicosis
drugs steroids oral contraceptives, ephedrine containing compounds (decongestants)
Miscellaneous raised intracranial pressure, burns, hypercalcemia, immobilization, autonomic
Guillain-Barr, polio.
Primary (5-93%):
Essential hypertension profile: age > 12 years, female > male, family history of essential hypertension,
obesity, excessive salt intake Hypertension is mild and examination is normal including no sign of end
organ hypertensive damage.

The younger the age at diagnosis of hypertension and the greater the severity of the hypertension, the
more likely it is that the hypertension is secondary rather than primary.
All patients with BP > 99th percentile, whether symptomatic or not, obese or lean, should be
investigated and treated,

History:
Often asymptomatic. Other: headaches, seizures, cardiac failure, stroke, Bells palsy, failure to thrive,
symptoms of the primary disease, drug ingestion. History of weight gain (Cushings), or weight loss
(thyrotoxicosis, phaeochromocytoma). Family history: early hypertension, renal disease. Past history of
umbilical artery catheterization
Examination:
Growth parameters, anaemia, rickets, obesity, signs of primary disease e.g. Cushings, ambiguous genitalia,
goitre. Skin neurocutaneous syndromes, impetigo, vasculitis, facies elfin (Williams syndrome), moon
face (Cushings), cardiac - failure, cardiomegaly (chronic hypertension), abdomen masses: Wilms,
neuroblastoma, hydronephrosis, polycystic kidney disease, renal bruit, bladder (obstructive uropathy),
upper and lower limb blood pressures, femoral pulses coarctation, neurological Bells palsy,
encephalopathy, genitalia ambiguous in CAH.
Investigations:
Preliminary screen: - (no clues as to diagnosis)

Urinalysis (blood, protein, specific gravity) and mid stream urine culture renal disease
Chest X Ray, ECG +/- ECHO
CBC, Hb electrophoresis
Blood urea, creatinine and electrolytes (hypokalemia in hyperaldosteronism, hyperkalemia in renal
disease). Liddles syndrome (hyperkalaemic metabolic aklalosis and hypertension), Gordon syndrome
(hyperkalemic metabolic acidosis), serum calcium, phosphate, serum proteins, uric acid
Calculate GFR Schwartz formula (see Chapter 1
+/- Fasting blood sugar (diabetes suspected), fasting lipoproteins
Renal ultra sound (+ / - Doppler flow study of renal vessels) (See Chapter 1)
24 hour urine VMA- VMA levels increased by bananas, asthma, and a methyl dopa
Renal scan DMSA , Glucoheptonate, DTPA for scarring.
Results suggesting renovascular disease:
an asymmetric, non functioning kidney with a delayed time to maximum peak activity greater than
11 minutes, or less than 2 minutes to maximum activity after ACE inhibition;

99

asymmetric peak function;

unilateral cortical retention of tracer after ACE inhibition,
Decreased GFR in the ipsilateral kidney after ACE inhibition.
RADIONUCLIDE SCANS (EVEN IF CAPTOPRIL ENHANCED) ARE NOT 100% RELIABLE
IN EXCLUDING RENAL ARTERY STENOSIS (RAS)

Captopril enhanced renography:

99m TcDTPA, or DMSA renal scan a screening test for renovascular hypertension. Do baseline scan,
then Captopril 0.7/kg mg po (max 25 mg) given and scan repeated in 1 hour. A reduction in effective renal
plasma flow or GFR of > 40% may be helpful in identifying patients with critical RAS. (Paed Nephrol
1995 (9) 259 267). The scan is considered abnormal if a focal defect is seen or the differential function is
less than 45% (Eu J Nuc Med 20: 699 701 in Ped Neph 1995 (9): 387.
If the preliminary screen is normal and the profile for essential hypertension exists, the diagnosis is likely
to be essential hypertension, and further work-up may not be necessary. If the screen is normal, but the
essential hypertension profile is absent, investigate further.
Other investigations:
Renal :MCUG, CT abdomen, renal biopsy, renal angiography or digital subtraction angiography.
Renin sampling from renal veins and vena cava ( Ratio of > 1.5 between plasma renin activity
(PRA) values in the main renal veils is a good predictor of surgical cure in renal artery stenosis).
Phaechromocytoma: MIBG scan (123 I metaiodobenzylguanine scan phaeochromcytoma tissue,
angiography, CT scan
Aldosterone levels
o increased: urine mineralocorticoids, dexamethasone suppression test, adrenal scan
o reduced: other mineralocorticoids in urine and blood , cortisol response to ACTH and
dexamethasone
Throtoxicosis T4, TSH, T3 levels
Cushings cortisols
Cardiac - ECHO, angiography
Treatment:
Non pharmacological weight reduction, exercise, diet low sodium

Pharmacological (see Table)

Aim to reduce blood pressure to below 95% for age
Discontinue ineffective drugs in a multidryg regime
Choose drugs with different sites of action
The stepped care approach is seldom used in children
Is combined with the non pharmacological treatment

Mild hypertension:
Hydrallazine + /- diuretic(Furosemide if renal function abnormal, thiazides if function normal)
Moderate hypertension:
Hydrallazine / B blocker / diuretic
ACE inhibitor / diuretic
Other second line drugs: Prazocin, nifedipine, -methyl dopa (also used in severe hypertension)

100

Severe hypertension:
Minoxidil + diuretic + second line drugs : Prazocin, nifedipine, -methyl dopa
Phaenoxybenzamine and phentolamine or prazocin phaeochromocytoma
Hypertensive emergencies (see Table 3)
Nifedipine, Hydrallazine, Minoxidil, Diazoxide, Sodium nitroprusside, Labetalol, Esmolol

101

Table 3
Antihypertensive drug therapy for hypertensive emergencies in children
Drug

Dose

Onset of action

Comments

Hydrallazine

0.2 0.4 mg/kg IV titrated

or bolus or IM
or IV infusion 0.75 5ug
/kg/min

10 30 min

May be repeated twice if no response

Give q 4h when bolus

Nifedipine

0.25 0.5mg /g po

Within2030 min

May be repeated twice if no response

Minoxidil

0.1 0.2 mg/kg po

Diazoxide

2.5 5 mg/kg (rapid IV

bolus) maximum 150 mg
/dose
or 0.25 5.0ug/kg per min
by infusion
0.5 1 ug/kg/ min IV
infusion initially may be
increased stepwise to
8 ug /kg/min maximum

1-3 mins

Can be repeated q 3 4 hourly

S/E hyperglycemia, salt and water
retention

Within seconds

Light inactivated ICU required

cyanide and thiocyanate toxicity with
use > 72 hours or in renal failure may
cause raised intracranial pressure

Labetalol

0.53 mg/kg/hr IV infusion

5-10 mins

A and B blocker contraindicated in

asthma / may worsen heart failure

Nicardipine

0.5 -5ug /kg/ min IV

infusion

Within min

Calcium channel blocker may increase

cyclosporin levels can be diluted up to
50 mg in 100ml by peripheral vein

Clonidine

50 300ug /kg/min IV
infusion

Within seconds

Cardioselective B blocker not

compatible with NaHCO3 avoid if
asthma

Enaprilat

0.005 0.01 mg/kg IV

q 8 24 hourly
1.25 mg IV q 6h
adolescents and adults

Within 15 min

ACE inhibitor contraindicated if

severe renal artery stenosis present or
suspected

methyldopa

5 10 mg /kg (max
500mg) IV in 50 cc D5W
over 30 60 min q 4 8
hrly

1 hour

Phentolamine

0.1 0.2 mg /kg IV

A blocker - phaeochromocytoma

Reserpine

0.02 0.07 mg/kg IM

q 2 3 h (max2.5mg/dose)

Rarely used
nowadays
recommended for children

Sodium
nitroprusside

Maximum initial dose 5 mg (q4h prn)

not

102

Table 4.

Antihypertensive drugs for chronic hypertension in children

Drug

Dose
mg/kg/day

Dosing
interval

Comments

Labetalol

1-3

q 6 12 h

/ blocker (contraindicated in asthma)

Phenoxybenzamine
Prazosin (Minipres)

1-4
0.05 0.5

Q 12 h
Q 6-8 h

blocker - paheochromocytoma
blocker

Atenolol

1-8

Q 12 24 h

blocker (contraindicated in asthma)

18
40 mg /dose
(max 480mg/day)

Q 6 12 h
Q q 12 h

blocker (contraindicated in asthma)

Child
Adult / adolescent

Clonidine

0.05 0.6 mg

Q6h

agonist

Nifedipine
Nifedipine XL

0.25 3
0.25 - 3

Q46h
Q 12 24 h

Calcium channel blocker

sublingual drug actually only works when

swallowed

Isradipine

0.05 0.15mg/kg/ dose

max 0.8mg/kg/day
max daily dose 20mg
0.1 0.3mg/kg/dose
max 0.6 mg/kg/day
max daily dose 20mg

Q68h

Propranolol

Amlodipine

Q12 - 24

Calcium channel blocker

Tablet can be suspended in water. Long acting
allow 5 7 days for dose adjustments flushing
headache, lower extremity oedema, fatigue

1.5 6

Q 8 12 h

ACE
inhibitor cough may occur
angioneurotic oedema potentially fatal allergic
reaction to ACE inhibitors watch for
hyperkalemia

0.15 0.5
2.5 40 (mg/day)

Q 12 24 h
Q 12 24 h

ACE inhibitor
Children
Adolescents / adults

1.5 - 3mg/m2
2.5 10 mg /day

Q 12 - 24
Q 24 h

ACE inhibitor
Children
Adolescents / adults

Hydrallazine

0.75 7.5
(maximum 200mg/day)

Q 6h

Vasodilator lupus like syndrome

Max dose 7.5mg/kg/dy or 200mg
whichever is less

Minoxidil

0.1 - 2

Q 8 12 h

Vasodilator hypertrichosis fluid retention

pericardial effusion

methyldopa

10 - 65

Q 8 12 h

Toxicity in renal failure Peak effect in 7 days

S/E depression, nasal congestion

Captopril

Enalapril

Rimipril

103

Table 4 ctd
Antihypertensive drugs for chronic hypertension in children ctd
Dose
mg/kg/day

Dosing interval

Comments

Furosemide

1 - 12

Q 4 12 h

Loop diuretic
Ototoxicity in high doses

Bumetanide

0.02- 0.3

Q 4- 12 h

Hydrochlorothiazide

1-3

Q 12 24 h

Thiazide not for use in renal failure

Bendrofluazide

0.1 0.3

Q 12 24 h

Metolazone

0.1 -3

Q 12 24 h

Spironolactone

1-3

Q 6 12 h

Aldosterone antagonist
Mineralocorticoid excess states S/E
hyperkalemia late onset

Triamterene

2-3

Q 6 12 h

Mineralocorticoid excess states eg

Liddles syndrome S/E hyperkalemia

Drug:
Diuretics

Table 5
Oral antihypertensive agents for infants
Drug

Dose

Interval

Comments

Captopril

< 6 months: 0.01 0.05 mg/kg per

dose
> 6 months as for child (maximum 6
mg/kg/day)

Q8h

Drug of choice for most neonatal

HTN monitor serum creatinine
and K+

Clonidine

0.05 0.1 mg/dose

Q 12 8 h

S/E dry mouth and sedation

rebound hypertension with
abrupt discontinuation

Hydralazine

0.25 1.0 mg/kg/dose

(maximum dose 7.5 mg/kg/day)

Q86h

Suspension stable up to 1 week;

S/ E tachycardia & fluid
retention; lupus like syndrome
possible in slow acetylators

Isradipine

0.05 0.15 mg/kg/dose

maximum 0.8 mg/kg/day

Q6h

Amlodipine

0.1 0.3 mg/kg/dose

max 0.6mg/kg/day

Q 12 h

Ca channel blocker
Suspension may be
compounded; useful for both
acute and chronic HTN
Less likely to cause sudden
hypotension than isradipine can
be suspended

104

Table 5 ctd
Oral agents for hypertension in infants - ctd.
Drug

Dose

Interval

Comments

Labetalol

1 mg/kg/dose
max 10 mg/kg/day

Q 12 8 h

Monitor HR / avoid in infants with

BPD and / or bronchospasm

Sprionolactone

0.5 1.5 mg/kg/dose

Q 12 h

Monitor electrolytes

Minoxidil

0.1 0.2 mg/kg/dose

Q 12 8 h

Used for refractory HTN

Propranolol

0.5 1.0mg/kg/dose
max 8 10 mg/kg/day if HR
normal

Q8h

Avoid in infants with BPD and

bronchospasm

References:
Antihypertensives for infants and fetal BP values: - Pediatr Neph (2000) 14: 332 341
Antihypertensive agents:
calcium channel blockers Pediatr Neph (2000) 15: 302 316
amlodipine Pediatr Neph (2000) 14: 1083 1087
nicardipine Pediatr Neph (1998) 12 40 42
loop diuretics Pediatr Neph (1998) 12: 603 616
ACE inhibitors
Enalaprilat Pediatr Neph (2001) 16: 85 86
Rimipril Pediatr Nephr (2000) 15: 113 118
Treatment of hypertensive emergencies in children
Pediatr Neph (2000) 14: 422 427
Pediatrics (1996) 98: pg 655 Task force update
Treatment of hypertension in children
Pediatrics (1996) 98: pg 656
Pediatr Nephrol (1987) 1: 50 58
Pediatric Nephrology 4thEdition pages 1038, 1039, 1046
Hypertension in children investigation and treatment
Pediatr Nephrol (1987) 1: 59 68
Pediatric Nephrology 4th Edition Barratt, Avner, Harmon eds Lippincott Williams & Wilkins Pub.
1999 edition / Chapters 60 63 / pages 959 1049
Captopril studies for renovascular hypertension
Pediatr Nephrol (1991) 5: 42 44
Ped Nephrol (1995) 9: 259 269
Pediatr Nephrol (1997) 11: 366 372

105

CHAPTER 14
DISORDERS OF ACID / BASE BALANCE
Acid / base homeostasis is maintained by a combination of metabolic and respiratory factors. Although the
first line of defense is the buffer system and respiratory factors, final correction rests with the kidney. For
the purposes of investigation, measurement of the pCO2 reflects the respiratory component and HCO3- the
metabolic component.
Acid base profile is best assessed by:
Measurement of pH, pCO2, HCO3 (arterial or venous blood gases)
Measurement of anion gap in plasma and urine -(measure serum Na, Cl and HCO3,and urine Na,
K, Cl )
Consulting an acid / base nomogram (See Figure 1)
Normal values
PH, pCO2, HCO3 (see Chapter 1)
Anion gap (blood) = [Na ] - [Cl + HCO3] = 8 16 mEq/l
Useful in evaluating metabolic acidosis (see Figure 2)
Anion gap (urine) = [UNa + UK] - [U Cl ]
Useful in distinguishing proximal from distal renal tubular acidosis (RTA)
Measures, indirectly, the urine concentration of ammonium in a patient with hyperchloraemic metabolic
acidosis
Negative urine anion gap [Cl >> Na +K] - GI or Renal loss of HCO3
Positive urine anion gap [Cl < Na + K] - Distal acidification defect
Common acid / base abnormalities
Type

pH

pCO2

Respiratory acidosis (acute)

N or slightly

Respiratory acidosis (chronic)

(slightly)

Respiratory alkalosis (acute)

Respiratory alkalosis (chronic)

HCO3

N or slightly
N or

Metabolic acidosis
Metabolic alkalosis

N or

106

Figure 1
Acid Base
Nomogram

An in vivo acid-base nomogram for clinical use. Usually acid-base values falling within a shaded band
indicate a single disturbance. Acid base values falling outside shaded bands indicate there are at least
two acid base disturbances. (From Arbus GS. An in vivo acid-base nomogram for clinical use. Can
Med Assoc J 1973; 109: 291)
Guidelines:
Chronic respiratory acidosis:
For every 3mmHg increase in pCO2

- HCO3 increases by about 1Eq/l (3:1 ratio)

Metabolic acidosis:
For every 1mEq/l decrease in bicarbonate

- pCO2 decreases by 1mmHg (1:1 ration)

In simple disturbances of acid base balance

- CO2 and HCO3 change in the same direction

In mixed disturbances of acid base balance

- CO2 and HCO3 change in opposite directions

Respiratory acidosis impaired ventilation Rx ventilation not bicarbonate

Respiratory alkalosis hyperventilation Rx correct primary cause

107

Metabolic alkalosis Rx primary cause

Causes include
Hypochloremia
Bicarbonate overdose
Volume depletion (eg diuretic overdose)
Hypokalemia (eg Bartter syndrome)
Phosphate excess
Metabolic acidosis - serum bicarbonate < 20mEq/l
Figure 2:

Evaluation of Metabolic Acidosis

Anion Gap
Normal

Increased

Organic acids
Lactate shock, hypoxia
Ketoacids diabetes
Organic acidopathies
eg Propionic acidemia

Exogenous acid load

Salicylates
Paraldehyde
Methanol
Ethylene glycol

Uraemia
Check urine pH
< 5.5

GI bicarbonate
Losses

> 5.5

Proximal RTA
in severe acidosis

Ingestion of acid with Cl as anion

e.g NH4Cl, arginine or lysine HCL

RTA

severe acidosis or NH4Cl (Acid) loading test

UpH
<5.5
Proximal RTA

UpH
>5.5
Distal RTA

108

Figure 3:

Evaluation of hyperchloraemic metabolic acidosis and negative urine anion gap

Negative urine anion gap

[Cl > Na + K]

GI HCO3 loss

Proximal RTA

History
Urine Na

HCl intake
History

Acid NH4 load

UpH < 5.5
Sodium bicarbonate load
FE HCO3 > 10 15%
U-B pCO2 > 20 mmHg
Proximal RTA
Look for other tubular defects
FE HCO3 fractional excretion of bicarbonate; U-B PCO2, urine to blood pCO2 gradient

From Renal tubular acidosis - Rodriguez-Soriano and Vallo. Pediatr Nephrol (1990) 4: 273

109

Figure 4:

Evaluation of hyperchloraemic metabolic acidosis and a positive anion gap

Positive urine anion gap

[Cl < Na + K]
Distal renal defect
Plasma K
Normal Decreased

Increased
Acid load

UpH >5.5

>5.5

<5.5

Sodium bicarbonate load

FE HCO3 <5%

< 5%

U-B pCO2 < 20mmHg

< 20mmHg

Distal RTA

>5 to 10%
> or < 20mmHg
(depends on GFR)
Hyperkalaemic RTA

Secretory defect

Voltage defect

?hypoaldosteronism-TTKG

Look for nephrocalcinosis,

Hypercalciuria and hypocitraturia

Look for Na
transport defect

? renal disease

From Renal tubular acidosis Rodriguez-Soriano andVallo. Pediatr Nephrol (1990) 4:273

Renal tubular acidosis:

Definition: metabolic acidosis secondary to transport defects in the reabsorption of bicarbonate, the
excretion of hydrogen ions or both
relatively normal GFR
hyperchloraemic metabolic acidosis
normal plasma anion gap
not to be confused with uraemic acidosis advanced renal failure/ normochloraemic metabolic
acidosis and increased plasma anion gap

110

Classification of RTA
Proximal (Type 2)
caused by impairment of HCO3 reabsorption in proximal tubule
decreased renal HCO3 threshold
able to acidify urine to pH < 5.5 in severe metabolic acidosis (when plasma HCO3 sufficiently low)
requires large amount of bicarbonate for correction as fractional excretion of bicarbonate is high
(10 15%)
aetiology: isolated or accompanied by other tubular defects (Fanconi syndrome)
characterized by growth retardation
rickets and osteomalacia never seen except with hypophosphataemia in Fanconi syndrome
nephrolithiasis and urolithiasis never occur even in presence of hypercalciuria
hypokalaemia restricted to Fanconis syndrome
Fanconi syndrome multiple tubular defects: generalized aminoaciduria, renal glycosuria,
phosphaturia, bicarbonaturia (proximal RTA), hyperkaliuria, sodium wasting, uricosuria, proteinuria,
and hyposthenuria, growth failure and vitamin D resistant rickets
Distal (Type 1)
caused by impairment of distal acidification usually failure of H+ pump
characterized by inability to maximally reduce urine pH (<5.5) in systemic acidaemia
impaired NH4 excretion
HCO3 reabsorption is quantitatively normal, but some bicarbonaturia may exist (<5% of filtered load)
less bicarbonate is required for correction
K usually normal or decreased
with voltage dependent defect, impaired K secretion results in hyperkalaemia - Hyperkalaemic
distal RTA (Type 4 RTA)
characterized by growth retardation, polyuria, hypercalciuria, nephrocalcinosis, lithiasis and K
depletion
usually primary (genetic defect) in children and acquired in adults often with autoimmune disease
Combined proximal and distal RTA (Type 3)
features of both proximal and distal RTA
marked reduction in tubular reabsorption of filtered HCO3 but ability to acidify the urine maximally
despite severe systemic acidaemia
usually a transient phenomenon in infants and young children with primary distal RTA
Hyperkalaemic RTA (Type 4)
acidification defect mainly caused by impaired renal ammoniagenesis
characterized by normal ability to acidify urine after an acid load, but subnormal acid excretion due to
very low rate of NH4 excretion.
Most frequently seen in children with hypo- or pseudohypo- aldosteronism
May be isolated or found with chronic renal parenchymal damage
Nephrocalcinosis and lithiasis are absent
Bone lesions are seen with uraemic patient
Hyperkalemia always present

111

Aetiology of Proximal and Distal RTA

Proximal

Distal

With Fanconi syndrome

Idiopathic

Inborn errors of metabolism

(eg galactosaemia, cystinosis)

Auto immune (SLE)

Chronic hypocalcaemia with secondary

hyperparathyroidism
eg vitamin D deficiency and bowel disease

Inherited sickle cell disease, Marfan synd

Drugs eg lead

Nephrocalcinosis 20 to hyperparathyrodism, hyperthyroidism, Wilsons

disease

Renal nephrotic syndrome, medullary

cystic disease

Drugs Lithium, amphotericin B

Isolated defect of proximal HCO3 reabsorption

Idiopathic
Acetazolamide

CLINICAL EVALUATION OF A PATIENT WITH SUSPECTED ACID-BASE DISTURBANCE

History:
Polyuria, polydypsia, failure to thrive, recurrent fevers, renal stones, sickle cell disease, SLE, drug
ingestion
Examination:
Growth parameters, BP, hydration, stigmata of syndromes, rickets
Investigations:
Blood urea, creatinine and electrolytes (including bicarbonate), serum calcium, phosphate, albumin,
alkaline phosphatase, venous blood gases pH, pCO2, and bicarbonate (See Chapter 1)
Urine:
PH (Chemical Pathology by special arrangement) dipstix UpH is not accurate
Urinalysis protein, sugar, blood, and microscopy for cells and casts
Clinitest for reducing sugars
Amino acid screen (Chemical Pathology)
Spot urine calcium, sodium, potassium, phosphate, protein, creatinine +/- 24 hour urine phosphate calculate tubular reabsorption of phosphate, hyperphosphaturia, check for hypercalciuria, and
excessive sodium and potassium loss in face of hypo- natraemia / hypokalaemia (See Chapter 1)
Urine specific gravity (fasting if safe to do so) assess concentrating ability
If Type 4 RTA suspected: add urine and plasma osmolality to calculate TTKG (See Chapter 1)

112

Management of metabolic acidosis

Treat underlying cause
Correct acidosis if HCO3 < 12mEq/l or pH < 7.2 by formula below:
HCO3 required = [HCO3 desired - HCO3 initial] x 0.6 x body weight (kg)
HCO3 desired = 12 mEq/l

Give half over 10 15 minutes and the remainder as an infusion over 2 3 hours.
Reassess acid-base status after treatment
Do not infuse with calcium containing preparations (precipitation)

Treatment of RTA
Treat underlying cause if identified
Give bicarbonate supplements sufficient to maintain serum bicarbonate at 20 25 mEq/l to ensure
optimal growth. Sodium bicarbonate (baking soda) is used, though citrate preparations are sometimes
available
Proximal RTA will require more bicarbonate supplementation than distal RTA (10 25 mEq/kg/day)
as opposed to distal RTA (5 15mEq/kg/day). K supplements may be needed in Types 1 and 2 RTA
as K loss in the urine occurs
Follow growth height and weight
Regular measurement of bicarbonate levels, renal function and urine calcium /creatinine ratios
+/- abdominal ultrasound for renal length and calcification, if nephrocalcinosis present at diagnosis
+/- plain abdominal X (PA) for following nephrocalcinosis
Type 4 RTA + / - mineralocortoids (Fludrocortisone), +/- K binders (Resonium A)
FORMAL PROTOCOL FOR LABORATORY EVALUATION OF SUSPECTED RTA
1.

Make prior arrangement with Chem Path for measurement of urine pH and chloride, and ICU for blood
gases

2.

No food after midnight. Discontinue alkali therapy for at least 6 12 hours before test (or ideally
perform the test when spontaneously acidotic).

3.

At 8 am

record height, weight, body surface area (m2) (see Chapter 1), BP, pulse and hydration
blood: electrolytes, urea, creatinine, bicarbonate, venous blood gas heparinized syringe for pH,
pCO2, and calculated bicarbonate (ICU) +/- plasma osmolality (Type 4 RTA)
urine: spot Na, K, Cl ,Ca, Creatinine, phosphate, amino acid screen, pH (Chem Path)
specific gravity (refractometer or hygrometer), dipstix for protein, blood and sugar
microscopy (centrifuged) for cells, casts)

4.

Calculate urine and blood anion gap (see above)

5.

Follow Figures 2 4 using urine anion gap to assist in diagnosis

6.

Generalizations to aid evaluation:

If urine pH < 5.5 and plasma bicarbonate < 18 mEq/l - likely proximal RTA
If urine pH > 5.5 and plasma bicarbonate < 18 mEq/l likely distal RTA
If urine pH > 5.5 and plasma bicarbonate > 18mEq/l < 20mEq/l ? distal RTA do NH4 Cl acid
loading test

113

Ammonium chloride (Acid) loading test

0800

IV D5 in normal saline at 50ml/m2/hr with oral fluids ad lib and normal diet

0900

NH4 Cl 100mg / kg po in gelatin capsules or lemonade (order from pharmacy)

1000

urine pH

1100

urine pH

1200

urine pH, serum electrolytes, urea, creatinine and bicarbonate, and venous gases for bicarbonate
pCO2 and pH

1300

urine pH

1400

urine pH, blood tests for 1200

Peak effect is 4 hours after dose.

Abort test when serum bicarbonate is < 15 mmol/l
Interpret results as per figure 3 and Generalizations above

References:
1. Renal and electrolyte disorders 2nd edition (1980). Schrier ed. Little, Brown and Co Pub: 115 158,
159 182
2. Renal tubular acidosis in children. McSherry. Kidney Int (1981) 20: 799 809
3. Pediatr Nephrol (2000) Rodriguez- Soriano. 14: 1121 1136. New insights into the pathogenesis of
renal tubular acidosis from functional to molecular studies
4. Pediatr Nephrol (1990) 4: 268 275 Rodriguez-Soriano and Vallo. Renal tubular acidosis
5. Residents Handbook Hospital for Sick Children 7th edition. Abelson and Smith (1987), pages 142
145, 394 - 395

114