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Chronic Kidney Disease

DR.MGM
BCPS
Definition

 a state of irreversible kidney damage and/or


reduction of kidney function, which can lead to
future decreases in kidney function.
Stages of chronic kidney disease

Stage Description GFR (mL/min/1.73 m2)

1 Kidney damage with normal or ↑ GFR ≥ 90

2 Kidney damage with mild ↓ GFR 60-89

3 Moderate ↓ GFR 30-59

4 Severe ↓ GFR 15-29

5 Kidney failure <15 (or dialysis)

Chronic kidney disease is defined as either kidney damage or GFR <60 mL/min/1.73 m2 for 3 months. Kidney
damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine
tests or imaging studies.
 Normal levels of GFR vary with age, gender,
and body size.

 A reduction in GFR implies a decrease in the


number of functioning nephrons
Normal GFR in children and young adults
Mean GFR ± SD
Age (gender)c Schwartz equation mL/min/1.73m2
GFR=0.33*(Length/SCr) in
Preterm
1 week (males and females) 40.6 ± 14.8
GFR=0.45*(Length/SCr) in
Term
2-8 weeks (males and
GFR=0.45*(Length/SCr) 65.8 ± 24.8
females)

>8 weeks (males and females) GFR=0.45*(Length/SCr) 95.7 ± 21.7

2-12 years (males and


GFR=0.55*(Length/SCr) 133.0 ± 27.0
females)

13-21 years (males) GFR=0.70*(Length/SCr) 140.0 ± 30.0

13-21 years (females) GFR=0.55*(Length/SCr) 126.0 ± 22.0

SCr: serum creatinine in mg/dL


Distribution of the etiology of chronic kidney disease (CKD) in children based
upon age
Etiology
 Congenital renal anomalies were present in 57
percent of cases.
 Glomerular disease was present in 17 percent of
patients.
 Other causes accounted for approximately 25
percent of cases.
CLINICAL PRESENTATION
 Early stages of CKD  asymptomatic.
 Direct kidney injury or disease.
 Incidental findings of an elevation in the serum
creatinine concentration and/or abnormalities on
urinalysis.
 Detection of congenital or structural anomalies by
imaging studies.
 Poor growth.
 Symptoms and/or signs of severe renal impairment.
 Systemic symptoms and findings due to a concurrent
systemic disease
COMPLICATIONS OF CKD
 Disorders of fluid and electrolytes
 Renal Osteodystrophy
 Anemia
 Hypertension
 Dyslipidemia
 Endocrine abnormalities
 Growth impairment
 Decreased clearance of renally excreted substances
from the body (uremia).
Fluid and electrolyte abnormalities
Fluid and electrolyte abnormalities
Sodium and water balance
Usually is maintained untill GFR <10-15
CKD 2-3 are less able to respond to rapid infusions
of sodium & are prone to fluid overload

 Hyperkalemia
Reduced GFR  inadequate potassium excretion &
decreased delivery of sodium to DT.
COMPLICATIONS
Metabolic acidosis
CKD 3 
1. Ammonium excretion begins to fall.
2. Reduction in titratable acid excretion (primarily
as phosphate).
3. Decreased bicarbonate reabsorption.
4. Body utilizes bone to buffer the excess
hydrogen ions.
COMPLICATIONS
Renal Osteodystrophy:
 Decreased renal clearance of phosphorus resulting in
retention of phosphate and elevation of serum
parathyroid hormone (PTH)
 Decreased production of Calcitriol.
 CKD2  reduced calcitriol level & elevated PTH
 CKD3  Subtle signs of bone.
 bone pain, difficulty in walking, and/or skeletal
deformities with more advanced disease.
COMPLICATIONS
Anemia:
 Normochromic, normocytic. Due to reduced renal
erythropoietin production
 Microcytosis may reflect iron deficiency or
aluminum excess
 Macrocytosis may be associated with vitamin B12 or
folate deficiency.
 Occurs at a GFR of 30-58ml/min/1.73m².
COMPLICATIONS
Hypertension:
 Volume expansion
 Activation of the renin-angiotensin system.
 May be due to medications used to treat the
underlying renal disease.
 can be present in the earliest stages of CKD and its
prevalence increases with progressive declines in
GFR..
COMPLICATIONS
Dyslipidemia and atherosclerosis:
 Young adults (25 to 34 years) with CKD have at least a 100-
fold higher risk for CVD related mortality compared to the
general population.
 40 to 50 % of patients with CKD have triglyceride levels
greater than 200 mg/dL (2.26 mmol/L).
 20 to 30% have total cholesterol levels greater than 240
mg/dL (6.2 mmol/L), 10 to 45 % have LDL cholesterol
levels greater than 130 mg/dL (3.4 mmol/L).
COMPLICATIONS
Dyslipidemia and atherosclerosis:
 lipoprotein lipase activity is reduced in advanced
renal failure; the increase in parathyroid hormone
secretion may play a contributory role.
 A circulating lipase inhibitor also may be retained in
renal failure.
COMPLICATIONS
Endocrine Dysfunction:

 Growth hormone metabolism


changes in the plasma concentration of GH, its
release, and its end-organ responsiveness due to
insulin growth factor binding proteins.
COMPLICATIONS
Endocrine Dysfunction:

 Thyroid function
alterations in the production, distribution, and
excretion of thyroid hormones.
Sick euthyroid syndrome: low T4 and T3, a normal
TSH level, normal or decreased TBG levels or TRH
stimulation test results.
COMPLICATIONS
Endocrine Dysfunction:
 Gonadal hormones
Delayed puberty ( average delay 2.5 years)
 In males, reduced levels of free testosterone,
dihydrotestosterone, adrenal androgens, and
increases LH & FSH
 Postpubertal females low estrogen, elevated LH and
FSH, and loss of the LH pulsatile pattern. These
disturbances result in anovulation.
COMPLICATIONS
Growth impairment:
 Metabolic acidosis

 Decreased caloric intake

 Renal osteodystrophy

 Alterations in GH metabolism
COMPLICATIONS
Uremia: With the onset of ESRD
Uremic state:
 anorexia
 nausea,
 vomiting
 growth retardation
 platelate dysfunction
 pericardial disease
 peripheral neuropathy
 central nervous system abnormalities ranging from
loss of concentration and lethargy to seizures,
coma and death.
COMPLICATIONS
Neurodevelopment
 Neurologic findings range from seizures and severe
mental retardation to subtle deficits resulting in poor
school performance.
 Uremia, malnutrition & Aluminum.
Frequency by CKD stage* (GFR mL/min 1.73 m2)
Assessment/tests CKD stage 5 (GFR <15 or
CKD stage 2 (GFR 60 to 89) CKD stage 3 (GFR 30 to 59) CKD stage 4 (GFR 15 to 29)
replacement therapy)

Kidney replacement therapy


Assessment of GFR[1] 6-12 months 3-6 months 1-3 months
(if uremia present)

Height/length; Height z-
3-6 months 3-6 months 3-4 months 1-3 months
score[2,3]

Weight (dry wt if on dialysis)[2,3] 3-6 months 3-6 months 3-4 months 1 monthly

Head circumference (until 36


1-3 months 1-3 months 1-2 months 1-2 months
months of age)[2,3]

Weight/height index[2,3] 3-6 months 3-6 months 3-4 months 1-3 months
Dietary interview[2,3] 6-12 months 6 months 3-4 months 1-3 months
Serum electrolytes and
6-12 months 6 months 1-3 months 1-3 months
albumin[2,4]

Blood pressure measurement[5] Performed at each health encounter

Performed within 3 months of


At presentation for new patients with hypertension. At least yearly in patients
Echocardiogram[4,6] who are on antihypertensive medications.
6-12 months commencing dialysis; and yearly
thereafter

For adolescent patients, evaluate on


presentation (when patient is stable);
Screen for dyslipidemia[7,8] at 2-3 months after a change in
For adolescent patients, screening at presentation with CKD and annually
treatment or other conditions
(cholesterol, LDL, HDL and
modifying serum lipid levels; and
triglycerides) every 6-12 months thereafter

Targeted screening recommended for children older than 2 years of age

6-12 months 6-12 months 3-6 months 1-3 months


Screen for anemia[9]
Monthly in patients on erythropoietic stimulating agents

Serum calcium, phosphorus, and


6-12 months 3-6 months 1-3 months 1-3 months
total CO2[10,11]

PTH and alkaline


6-12 months 3-6 months 1-3 months 1-3 months
phosphatase[10,11]
Management
GENERAL PRINCIPALS
 Treat reversible renal dysfunction

 Prevent or slow the progression of renal disease

 Treat the complications of CKD

 Identify and adequately prepare the child/family


in whom renal replacement therapy will be
required
Management

reversible renal dysfunction

 Decreased renal perfusion


 Nephrotoxic drugs
Management
Slowing CKD progression
 progression of CKD is greatest during the two
periods of rapid growth: infancy and puberty.
 strict blood pressure control

 Proteinuria reduction

 Dietary protein restriction, lipid lowering


therapy, and correction of anemia.
Management
CKD Complications
1.Sodium & water retention:
dietary sodium restriction and diuretic therapy
 Sodium intake 1.2 – 1.5 g/day

 Diuretics: furosemide, thiazide diuretics.

Fluid & sodium supplementation


Management
CKD Complications
2. hyperkalemia:
 Low potassium diet.
 Administration of a loop diuretics.
 correct acidosis.
 formula can be mixed with kayexalate
 Renal replacement therapy must be considered if
conservative management fails to control
hyperkalemia.
Management
CKD Complications
3. Metabolic acidosis:
 guidelines by the K/DOQI working group are
to maintain the serum bicarbonate level at or
above 22 mEq/L
 Sodium bicarbonate is started at 1-2 meq/kg/d
Management
CKD Complications
4.renal osteodystrophy :
 Low phosphate diet.

 Administration of phosphate binders.

 Vitamine D replacement therapy .


Management
CKD Complications
5. Hypertension:
 The K/DOQI guidelines recommend a target
blood pressure of less than 90th percentile for
age, gender, and height, or less than 120/80
mmHg, whichever is lower.
 Non pharmacologic therapy
 Pharmacological therapy: diuretics, ACE
inhibirors, ARBs
Management
CKD Complications
6. Anemia:
Screening and evaluation of anemia
 Annual testing regardless of stage or cause of CKD
 Dx is made when Hgb level is below the 5th % of normal
adjusted for age & sex.
 Once detected:
* Red blood cell indices
* Reticulocyte count
* Iron parameters (serum iron, total iron binding capacity, percent
transferrin saturation [TSAT] and serum ferritin)
*Test for occult blood in stool
Management
CKD Complications
6. Anemia:
Treatment of anemia
1. K/DOQI guidelines recommend a target Hb between 11 and 12
g/dL, FDA recommend a Hb of 10-12
2. Iron therapy: targeted to maintain a TSAT ≥20 percent and serum ferritin
≥100 ng/dL.
Iron status should be monitored every 1-3 mon.
3. Erythropoiesis stimulating agent
• initial EPO dose in older children not receiving dialysis is 80 to 120 u/kg per
week
• Children < 5 years or receiving dialysis require higher doses (300 u/kg per
week).
• Hb should be monitored
Management
CKD Complications
6. Anemia:
Failure to respond to therapy
 Infection or inflammation
 Chronic blood loss
 Osteitis fibrosa /secondary hyperparathyroidism
 Aluminum toxicity
 Folate or vitamin B12 deficiency
 Malnutrition
 Hemoglobinopathies
 Hemolysis
 Carnitine deficiency (rare)
 Copper deficiency (rare)
Management
CKD Complications
7. Dyslipidemia:
 Evaluation is performed at presentation, and annually thereafter
or two to three months following a change in treatment.
Management
Lipid disorders
Lifestyle intervention for BMI <85th percentile for age and sex
Decrease intake of simple sugars
Fasting TG >150 Evaluate for secondary causes such as diabetes, thyroid disease, renal disease, and
mg/dl alcohol abuse
For TG >700 - 1000 mg/dL, consider gemfibrozil or fenofibrate if >10 years old to
prevent pancreatitis

Lifestyle intervention for BMI <85th percentile for age and sex
HDL <35 mg/dl Moderate to vigorous physical activity 60 minutes daily
Pharmacologic intervention not currently recommended for isolated low HDL

Nutrition training & life style changes


LDL ≥ 100 mg/dl Repeat LDL measurement
Start statin therapy if >10 years, goal LDL 130 mg/dL
Management
CKD Complications
8. Nutrition:
K/DOQI pediatric guidelines for nutrition recommend that the
nutritional status of children with CKD should be monitored on
a monthly basis for children younger than two years and every
three to four months for children older than two years of age
Management
CKD Complications
8. Nutrition:
 Dietary interview
 Weight
 Height or length
 Weight / height index & BMI`
 Mid-arm circumference and muscle circumference or area
 Skin fold thickness
 Head circumference for patients younger than three years of age.
Management
CKD Complications
8. Nutrition:
 The initial prescribed energy (calorie) for children with CKD
should be the recommended dietary allowance (RDA) for
chronological age.
 Protein restriction is not recommended in children.
 100 % of the RDA should be the goal for vitamins A, B, C, E,
K, and the minerals, copper and zinc
 Tube feedings
Management
CKD Complications
9. Growth:
criteria for initiating rHuGH in children with CKD
include all of the following:
 Height SDS that is more negative than -1.88 and/or a
height velocity SDS that is more negative than -2.
 Growth potential that is documented by open
epiphyses.
 There are no contraindications for rHuGH
Management
CKD Complications
9. Growth:
rHuGH is continued until the child reaches
the 50th percentile for mid-parental height,
achieves a final adult height with closed
epiphyses, or receives a kidney transplant.
Management
CKD Complications
10. Uremic bleeding
If undergoing a procedure or actively
bleeding:
 Desmopressin (0.3 mcg/kg)
 Cryoprecipetate (1 to 2 units/10 kg);
 Estrogen (0.6 mg/kg per day for 5 days)
 Correct anemia
Management
CKD Complications

10. Uremic pericarditis

 Seen in late stages of CKD


 Indicates the need for dialysis
Renal replacement
therapy
Renal replacement therapy
The registry of the North American Pediatric Renal
Trials and Collaborative Studies (NAPRTCS)
reports
 One quarter of children underwent preemptive
renal transplantation
 One half were started on peritoneal dialysis
 One quarter were started on hemodialysis
The choice among renal replacement
options is dictated by technical, social,
and compliance issues, and family
preference .