Far Eastern University – Nicanor Reyes Medical Foundation

PEDIATRICS 3A: NEPHROLOGY A

Dr. Matheus, MD

HEMATURIA
GROSS HEMATURIA:
- Bright red blood, clots in urine, or tea-colored urine
o Presence of clots usually suggest surgical, urological
problem (e.g. post glomerular disease)
o Tea-colored urine usually suggests the following:
§ Glomerular damage
§ Intake of drugs (E.g. metronidazole)
§ Hemoglobinuria
§ Myoglobinuria

MICROSCOPIC HEMATURIA:
- > 5 RBCs/hpf on more than two occasions
- Significant Hematuria
o RBC in the urine is > 5 (Other literature, >3)
§ The implication in lower cut-off is that you will Diagram on several causes of hematuria
be screening for more people and getting work- Glomerular diseases are usually the causes of END STAGE
up for patient is that are normal RENAL DISEASE
§ The implication in higher cut-off (>5) is that the
lesser people will be screened, possibly missing Four diseases in focus in this lecture include:
patients who might have significant hematuria - Post-Infectious Glomerulonephritis
- Persistent Hematuria - Nephrotic syndrome and benign cases of proteinuria
o Defined as three positive urinalysis - Henöch-Schonlein Purpura (HSP) Nephritis
§ Repeat urinalysis is usually done if results are - Urinary Tract Infection in children
equivocal
o Three positive urinalysis, based on dipstick and POST INFECTIOUS GLOMERULONEPHRITIS
microscopic examination over a 2-3 week period of
time GABS, Staph, Salmonella, Leptospirosis
§ Rationale: a single urinalysis would not suffice BACTERIAL
Group B Strep causes Gram(+) neonatal sepsis. If
to detect a significant hematuria
§ Test requires a 2-3 week period because RBC Gram (-), E. coli.
passage is not constant VIRAL Mumps, measles, chicken pox
• Levels may depend on the time of the
PROTOZAN Malaria
sample
o NOTE: three urinalysis are usually NOT REQUIRED
- Post-infectious glomerulonephritis is characterized by a
§ 1 urinalysis is enough + Determination of
previous infection prior to the onset of the nephritic
etiology if:
syndrome
• There is microscopic evidence of
- Immune complex reaction leading to nephritis
hematuria
- 2-12 years old, usually; no sexual predominance (M=F)
• Patient is already passing out tea-
- All events under the overview of post-infectious
colored urine
glomerulonephritis should be present.
- Test strips can detect 5-10 intact RBCs/mul or 2-5 RBCs/hpf - Infection -> Latent Period -> Nephritic syndrome (positive
o 2-5 RBCs/hpf is a positive test but does not necessarily hematuria and other manifestations of the nephritic
mean significant hematuria syndrome)
o POINT: test strips (qualitative) should be correlated
with microscopic findings (quantitative)
LATENT PERIOD (ASYMPTOMATIC)
- infection may have subsided, continued, on and off, or
**BENIGN FAMILIAL HEMATURIA: is presented as having normal infectious was already treated (most common)
renal function tests with RBC in the urine as the only abnormality

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 - Variable course:
o less than a week to 6 weeks (viral)
o 6 weeks, or even as long as 3 months (bacterial)
o Average of 10-14 days (Post-strep)
- Representative diseases:
o Post-streptococcal glomerulonephritis
o throat/skin infection
o Group A Beta Hemolytic Streptococcus (GABS)
§ typical strep serotypes in AGN / nephritogenic
strains include
§ pharyngitis: 1, 3, 4, 12, 25, 49
§ pyoderma: 2, 49, 55, 57, 60
Step that cause Rheumatic Fever are cardiogenic strains. AGN and
RF are caused by the same organism, but of different serotypes.
Some literature report the existence of RF and AGN
simultaneously in one patient, but there is still no consensus. . RF
and AGN are still treated separately in these cases.
PATHOGENESIS:
- Immune-mediated disease (circulating)
o trapping of circulating immune complexes (Ag-Ab
complex) in the glomeruli
o immune response causes glomerular nephritis
(secondary inflammatory response)
- Molecular mimicry
o between streptococcal and renal antigens
o renal Ags (resembling strep Ags) are being attacked
- In situ immune complex formation between anti-
steptococcal Abs and glomerular planted antigen (non-
circulating)
- Direct complement activation by steptococcal Ags
deposited in the glomeruli.
o Activation leads to chemotaxis, then the eventual
lysis of the cell (lysis, opsonization, chemotaxis)
CLINICAL MANIFESTATIONS
- If all s/sx are present but no hematuria, NOT NEPHRITIC.
- Gross or microscopic hematuria
PEDIATRICS 3A: NEPHROLOGY A
- Hematuria with proteinuria should lead you to considering
GLOMERULAR DISEASE.
- Edema starts at the perioribtal area, subsides, and goes to
the lower extremities, and may lead to anasarca
- Edema, HTN, dyspnea, HF are related to volume expansion
due to loss of renal function.
- Oliguria and azotemia are also secondary to loss of renal
function.
In pediatrics, hypertension is defined as BP above the 95th
percentile. Pre-hypertension, on the other hand, is defined as in
the range of 90-95th percentile. Less than 90 is normotensive.
LABORATORY EXAMINATION
- Urinalysis (24 hour urine determination)
o gross or microscopic
o proteinuria (<40mg/m2/hr) - varying degrees
§ at times, PSGN can reach nephrotic range
(according to Cañero Trans)
§ nephrotic range: >40mg
- Serum electrolytes (Na, L. Ca,P)
o hyponatremia (dilutional)
o hypocalcemia
o hyperkalemia - main excretion is through the kidney,
presently defunct in glomerulonephritis
o hyperphosphatemia
o hydrogen - increased
- ABG (assess Hydrogen ion handling)
- Renal Function Tests : BUN/Crea, eGFR
o BUN/Crea is used in the gross evaluation of renal
function
§ evaluation of the contribution of R and L
kidneys
§ e.g. Assuming both kidneys are normal in a
patient, if one kidney is removed, renal function
remains the same
o There may be a problem with renal function even if
BUN/ Crea is in normal range.
§ Crea only increases if GFR <50%; Crea may
present normally if GFR is >50%.
One does not simply say renal function is normal with BUN/Crea
in normal range
- Estimated GFR (eGFR) is best used to assess renal function
by 24-hour urine sample
o getting true GFR is quite tedious because of 24 hour
urine sampling, as well as the blood; availability may
also be an issue to acquiring true GFR
o compute for the estimation:
§ eGFR: Serum Crea (mg/dL) / length x constant
- ASO, neuramidase, DNAse
o Latent period - Due to high likelihood of treated
infection, physician may not be able to find findings
anymore, unless in cases of pyoderma.
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 § We may look or scars, scabs indicative of o Diuretics - Furosemide 1-2mg/kg/dose
previous wounds o Fluid restriction - correction of fluid also leads to
§ In strep throat, we cannot find observable correction of hyponatremia
findings; therefore, we do serological testing to o Doing away with potassium in diet, fluids and
document previous infection. medicines
o ASO - most common method to document previous - Maintain homeostasis by F&E
infection - Antihypertensives
§ not 100% accurate - Dialysis - last resort
§ only 80% (+) for pharyngeal infection
§ 60% (+) for pyoderma - lower accuracy if skin PROGNOSIS
One does not simply rule out Strep Infection with negative ASO - Good: more than 90% recover
- Throat swab/culture o C3 recovers in 6 weeks but can take as long as 3
- Skin lesion discharge culture - if still with active lesion months. If still decreased after 3 months, consider
- Serum C3, C4 continuous damage and warrants renal biopsy
o C3 is widely available - 3 phases:
o 90% will have low C3 due to direct complement o Acute: 1-2 weeks, s/sx renal dysfunction, edema,
activation. HTN
REVIEW! o Diuretic: oliguric to diuretic, (+)hematuria
What are the four proposed mechanisms for the pathogenesis of o Resolution/Recovery: hematuria (microscopic only)
PSGN? with proteinuria in 6 months
TRUE or FALSE: The cause of acute post-infectious § proteinuria should be absent in 6 months time)
glomerulonephritis is the immune complex deposition?
PSGN: ESSENTIALS FOR DIAGNOSIS:
- Identification of the primary infection (good history taking)
- Chest X-ray
- Establishing presence of latent period (history taking)
o In PSGN, cardiomegaly and
- Appearance of signs and symptoms of nephritis
equalization of vascular
- Evidence of previous or ongoing streptococcal infection
markings in the apical and
(ASO)
basal areas may suggest
o Appearance of s/s of nephritis and evidence of
congestion .
previous infection of strep should make you consider
major and minor jones criteria for RF
- Majority of cases - good prognosis and asymptomatic in
COMPLICATIONS
nature
- Volume overload
- Renal failure
PROTEINURIA: BENIGN (TRANSIENT) VERSUS PATHOLOGIC
- Electrolyte imbalance
o Hyponatremia - dilution due to volume overload
o Hypocalcemia - activation of Vitamin D (1,25-DHCC)
in the kidney does not happen anymore because of
AGN
o Hyperkalemia - d/t decreased renal excretion of K
o Hyperphosphatemia
o Increased Hydrogen
- Hypertensive crisis / encephalopathy

TREATMENT
- Primarily Supportive
- Penicillin for 10 days - standard treatment of PSGN (mild,
moderate or severe); drug available in IV or capsule
o oral preparations not tolerated by infants
o alternative drugs: Ampicillin, Amoxicillin, 1st gen
cephalosporins, Erythromycin
- Regulation of fluid - prevent fluid overload
ORTHOSTATIC/POSTURAL PROTEINURIA
- most common cause of persistent proteinuria in school
aged children and adolescents
- benign condition with increased protein excretion when
standing, and normalization of levels when supine

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 - measured by doing 24-hour urine collection (12 hours - there are immune and non-immune insults to the
ambulatory and 12 hours supine) podocyte that lead to foot process effacement of the
podocyte, a decrease in number of functional
NEPHROTIC SYNDROME IN CHILDREN podocytes, and altered slit diaphragm integrity
- Glomerular proteinuria results from the alterations in the - In idiopathic, hereditary, and secondary forms of
permeability of any of the layers of the glomerular capillary nephrotic syndrome, the end result is protein
wall to normally filtered proteins and occurs in a variety of “leakiness” across the glomerular capillary wall into
renal disease the urinary space
- Podocyte is the predominant cell of injury in most
glomerular diseases characterized by heavy proteinuria. According to the International Study of Kidney Diseases in
- 3 layers of the capillary wall act as the glomerular Children:
filtration barrier: Heavy proteinuria - ≥40 mg/m2/hr
o glomerular endothelial wall (primary event)
o glomerular basement membrane
Hypoalbuminemia - ≤2.5 gm/dL
o podocyte
§ body lies within the urinary space; cell attached normal: 3.5 - 4.5
to the GBM through its foot processes gm/dL
- GFB prevents proteins and large molecules from passing - Protein loss in the urine
from the capillary lumen into the urinary space. leads to hypoalbuminemia
à liver compensates by
- Disruption of GFB leads to passage of proteins across the
Hypercholesterolemia synthesizing more
capillary wall, leading to proteinuria.
/hyperlipidemia albumin using the same
- increased permeability of the glomerular capillary wall. pathway as cholesterol
which leads to massive proteinuria and hypoalbuminemia synthesis.
- **the podocytes plays a crucial role in the development of
proteinuria and progression of glomerulosclerosis - Cholesterol is retained,
Podocytes therefore high cholesterol
- highly differentiated epithelial cell located on the levels
outside of the glomerular capillary loop. - gradually builds up until
- functions: anasarca
Edema (only clinical
o structural support of the capillary loop
finding) - am: periorbital edema
o major component of the glomerular filtration
- pm: (-) periorbital but (+)
barrier to proteins pretibial edema
o involved in the synthesis and repair of the
glomerular basement membrane HISTOLOGIC DIAGNOSIS (PRIMARY DISEASE) IN RENAL BIOPSIES
- The foot processes are extensions of the podocyte that OF 521 CHILDREN:
terminate on the glomerular basement membrane.
The foot processes of a podocyte interdigitate with
those from adjacent podocytes and are connected by
a slit called the SLIT DIAPHRAGM.
o Slit Diaphragm is one of the major impediments
to protein permeability across the glomerular
capillary wall
o important component proteins of slit - Those in red show progressive disease despite treatment
diaphragm include: and eventually leads to End Stage Renal Disease.
§ nephrin
§ podocin Minimal Change NS is usually seen in young males (2-6 y.o.) with
§ CD2AP proteinuria without hematuria in urinalysis.
§ a-actinin 4
o Podocyte injury or genetic mutations of genes RESPONSIVENESS TO STEROID TREATMENT:
producing podocyte proteins may cause - Minimal Change Nephrotic Syndrome - most sensitive
nephrotic-range proteinuria o sensitivity of 93.1% (positivity)
o specificity of 72.2% (negativity)

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 CLINICAL CLASSIFICATION OF CHILDHOOD NEPHROTIC
SYNDROME
- Secondary - 10%
o systemic disease, drug, toxin, allergen, APSGN
- Congenital Nephrotic Syndrome
o Finnish
o <6 months, DDx of HIV
- Clinical Hallmark of Nephrotic Syndrome is EDEMA
FORMATION

EDEMA
- asymmetric and dependent (influenced by gravity
- Massive proteinuria (>40mg/m2/hr)
o (+) periorbital edema - composed of loose tissue
§ DDx: Cushingoid: (-) periorbital edema, with
sunken periorbital areas, (+) facial edema,
steroid facies
o (+) scrotal edema – benign
§ risk for infection due to friction on the sides of
the scrotum
§ infection spreads fast in edema
o (+) pitting edema - pretibial edema

- Problem with net absorption - arterial = decrease oncotic
pressure
- With decreased protein in the blood, Starling forces are
affected
o arterial side: increased net filtration
o venous side: deceased net absorption
CLASSICAL SYMPTOMS
- Periorbital edema - palpebral fissures are unequal
- taut skin
- scrotal edema
- pitting pedal edema (esp. in Minimal Change)
- Fluid does not stay long; interstitial hydrostatic pressure
goes up, forcing fluid to the lymphatics and eventually to
the venous circulation
PROTEINURIA (ALBUMINURIA)
- Dipstick: 4+ albumin
- Protein/Creatinine ratio: (random urine sample-screening
only)
o >200mg/mmol
o >2mg/dL
- 24-hour urine albumin determination (Gold Standard)
o (volume = clearance), discard 1st voided urine,
collect the next until the last voided urine
§ Time of collection of urine is essential: urine
formed (not just the urine excreted) during the
24-hour collection time is collected
o Through body surface area: >40mg/m2/hr
o Through weight: >50mg/kg/day
§ False (-) if missed collection
INVESTIGATION OF INITIAL PRESENTATION
- CBC with platelet count
o check for infection (increased WBCs), and
intravascular volume contraction (decreased
reabsorption) as evidenced by increased hematocrit
and thrombocytosis
- Serum creatinine, cholesterol, TPAG (according to ISKDC)
- Urinalysis
- 24-hour creatinine clearance / eGFR
- Renal Ultrasound (not mandatory; only if entertaining
Differential Diagnosis)
- Others:

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 o C3 (depends on the clinical features) - prognostic - Meta-analysis of dose and duration of prednisone showed
value that the risk of relapse was reduced by 40% with higher-
o Minimal Change Disease = normal C3 dose steroids.
o Primary Type: Membranous Proliferative Disease = o This suggests that increased doses of steroids and
Decreased C3 prolonged duration are important in reducing the
o Hepatitis B screening risk of relapse.
o Tuberculin test - Duration of initial prednisone therapy = 12 weeks
- Sustained remission and reduction of relapse rates if
SECONDARY NEPHROTIC SYNDROME alternate-day treatment is not stopped abruptly at 12
- Supporting laboratory exams exist for the primary disease weeks but tapered over the next 2-4 months.
(e.g. SLE with (+) tests for ANA, anti-dNASE, Anti-Sm)
STEROID-SENSITIVE NS DIET
CURRENT TREATMENT: - balanced diet
- International Study of Kidney Disease in Children(ISKDC) - Protein at 1.5-2.5 gms/kg for patients with persistent
- Arbeitsgemeinschaft fur Padiatrische Nephrologie (APN) proteinuria
- DOC: Prednisone o For growth and nitrogen balance
o High protein diets exceeding 2.5 grams/kg not done
STEROID TREATMENT REGIMEN: ISKDC VS APN anymore because it worsened renal symptoms
- ISKDC: 8 weeks (4 weeks daily and 4 weeks alternate day (lecture)
therapy) - Salt restriction: 1-2 gms/day - no added salt
o 2 months intensive treatment - Ensure physical activity and prevent excessive weight gain.
o 1st half (4 weeks daily): 60mg/m2 - Education regarding effects of high-dose steroids:
o 2nd half (4 weeks alternate): 40mg/m2 voracious appetite, central obesity, fluid retention,
- APN: 12 weeks (6 weeks daily, 6 weeks alternate daily) hypertension, DM, cataract
o 3 months intensive
o superior than ISKDC regimen EDEMA
o 1st half (6 weeks daily): 60 mg/m2 - Diuresis from treatment within 5-10 days
o 2nd half (6 weeks alternate): 40mg/m2 o Diuretics in NS is a double-edged sword which
After intensive treatment, steroids should be tapered slowly causes intravascular volume constriction because
with or without response body recognizes it as hypotension which can also
For preteens: dose can be as high as 80mg/m2 (lecture) eventually induce renal failure.
o Kidneys may mistake the volume contraction
STEROID RESPONSE caused by diuresis as a form of SHOCK.
REMISSION - proteinuria and edema subsides with 3 Magmamaganda si Kidney. More, more, more
consecutive (-) proteinuria (dipstick) oliguria. Nakow.
FREQUENT - 2-3 relapses in 6 months 3-4 relapses in o More RAAS stimulation, more vasoconstriction of
RELAPSE a year renal arteries. Kidney might shut down.
INFREQUENT - 1-2 relapses in a year - Oral furosemide 1-3 mg/kg daily for persistent edema and
RELAPSE weight gain of 7-10%
STEROID - (+) remission but with relapses after - Spironolactone 2-4 mg/kg daily for patients with
DEPENDENT tapering steroids prolonged and high dose furosemide requirements.
STEROID - still unresponsive after giving intensive - Albumin transfusion - should be done first before diuresis
RESISTANT course
to increase oncotic pressure.

2007 COCHRANE REVIEW

OTHER MEDICATIONS
- APN’s 12 week regimen vs ISKDC’s 8 week regimen
- Calcium Carbonate
o sustained remission of 49% and 19%, respectively
o for prolonged steroid use (>3 months)
o rate of frequent relapse at 29% vs 59%, respectively
o Counter Calcium-antagonizing effects of steroids
- Superiority of 12 week initial regimen
- Hyperlipidemia Medications
o High dose is offset by longer duration of remission
o not usually required for steroid sensitive NS
and infrequent relapse
o usually reserved for non-responders
o addresses steroid usage’s tendency to promote
atherosclerotic changes

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 - Isonizaid - for 6 months, for Mantoux positive only
- TB disease - treated with standard therapy
- Antacids - usually not necessary
STEROID SENSITIVE NS (MINIMAL CHANGE DISEASE)
- 80% will have one or more relapses
- 50% with either have a frequent relapses or be steroid
dependent
- Increasing age = Decreasing incidence of relapses
o Frequency of relapses decrease with time with 50-
70% being relapse-free after 5 years and about 85%
relapse-free at 10 years
- Early relapse after initial treatment and short duration of
remission increase risks for subsequent relapse.
- Patients with frequent relapses during childhood are more
likely to have disease persisting into adulthood.
COMPLICATIONS
- Thrombosis
o correction of hypovolemia and hemoconcentration
o Anticoagulation for thromboembolic episodes and
those at risk
- Hypovolemia - Emergency! Emergency!
o Abdominal pain, oliguria, cold peripheries, poor
pulse volume, hypotension, hemoconcentration,
usually minimal edema
o 20-25% salt
o Albumin 0.5-1.0g/kg/dose over 1-2 hours infusion
o Furosemide 1-2 mg/kg/dose
o Transfuse albumin first before diuretics
- Hyperlipidemia
o dietary advice
o HMG-CoA reductase inhibitors are effective but
experience is still limited (not usually necessary if
responsive to steroids)
o Increased risk for cardiovascular disease for Non-
Minimal Change Disease (NMCD) with persistently
heavy proteinuria and increased VLDL and LDL
- Infection - relapses with complaint of abdominal pain;
primary peritonitis
o cover for both gram (+) and (-) organisms until
cultures are available
o prophylactic oral penicillin 125-250 mg BID in an
edematous child
o Step pneumoniae is most common agent causing
peritonitis and septicemia
o Primary peritonitis is not full-blwon, (+) diarrhea
and discomfort
IMMUNIZATION
- Live vaccines (measles, polio boosters) not given to
patients on corticosteroids
o Can be given 4 weeks after cessation of treatment
- Killed vaccine may be given anytime
- 23-polyvalent pneumococcal polysaccharide vaccine
o given especially if prone to Strep. pneumoniae
infections (relapses associated with URTI)
o >2 years old
o variable response
o loss of antibody titer over time
- PVC 12
- Influenza A
o adequate Ab titer maintained at 6 months post-
vaccination
SUSCEPTIBLE NEPHROTICS
- Varicella exposure
o Zoster immunoglobulin within 72 hours from
exposure
o Acyclovir, if varicella develops
- Measles exposure
o Gamma globulin
PROGNOSIS
- Overall GOOD prognosis for Minimal Change
- Guarded prognosis for other primary types
IGA NEPHROPATHY
- Most common chronic glomerular disease worldwide
- Benign hematuria without systemic manifestations
- Characterized by a predominance of IgA within mesangial
deposits of the glomerulus
o (+) microscopic or gross hematuria
o (-) systemic manifestations
- Initially presents with significant microscopic hematuria
without HTN or edema. HTN and edema occurs only as
disease progresses.
- Natural history:
o initial and persistent microscopic hematuria, then
o gross hematuria, then
o eventually disappears, with URTI
- an immune complex disease caused by abnormalities in IgA
- familial clustering
- genome-wide linkage analysis: 6q22-23
- Other diseases with prominent IgA mesangial deposition
o Rheumatic Arthritis (RA)
o Ankylosing Spondylitis (AS)
o Reiter syndrome - arthritis, urethritis, bilateral
conjunctivitis
o Hepatic cirrhosis

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 CLINICAL MANIFESTATIONS
- Westerners present with gross hematuria; Asians (Japan)
present with microscopic hematuria and/or proteinuria
- Full-blown acute nephritic; full-blown acute nephrotic;
combined nephritic-nephrotic syndrome (sig. proteinuria
and hematuria)
- Gross hematuria may occur in association with URTI or GI
infection, loin pain.
o IgA has a protective role in URT and GIT
- IgA nephropathy: Gross hematuria may recur.
o Post-strep GN: Gross hematuria does not recur.
- Proteinuria is frequently in the nephritic range
(<1000mg/24hr) in patients with asymptomatic,
microscopic hematuria.
- Mild to moderate hypertension - subsequently
- Normal serum C3
- Serum IgA have no diagnostic value
o Only elevated in 15% of patients.
o (-) IgA will not r/o IgA nephropathy.
- Progressive disease develops in 20-30% of children at 15-20
years after onset.
o Majority show a benign course; however, 20-30% of
these patients end up in end stage renal disease
(ESRD).
PROGNOSIS
- isolated hematuria
GOOD
- isolated proteinuria
POOR - persistent hypertension
- diminished renal function
- heavy or prolonged proteinuria
- combination
WORSE - diffuse mesangial proliferation >5-8
mesangial cells affected
- extensive glomerular crescents (also
seen in RPGN)
- glomerulosclerosis
- tubulointerstitial changes i.e.
inflammation and fibrosis (chronic
indicator)
- *normal mesangial cells: 3/glomerulus
- ACEI and ARBS
o still under study concerning reduction of proteinuria
and retarding renal progression
- Prophylactic antibiotics and tonsillectomy have no proven
benefit.
- Renal transplantation (no absolute cure) or dialysis
- Allograft loss caused by IgA nephropathy in 15-30% of
patients causes recurrence.
HENOCH-SCHONLEIN PURPURA (HSP) NEPHRITIS
- IgA Nephropathy with SYSTEMIC MANIFESTATIONS
- also referred to as Anaphylactoid Purpura
- small vessel vasculitis characterized by a TETRAD
o purpuric rash
o arthritis
o abdominal pain
o glomerulonephritis
CLINICAL MANIFESTATIONS
- Purpuric Rash (hallmark)
o palpable purpura, symmetical, in gravity-dependent
areas (lower extremities) or pressure points
(buttocks)
o greater than macule; >1cm; elevated
o from red, becomes purplish, to yellow-brown, then
disappears
- Arthritis
o big joints (wrist, elbow, knees, ankle)
o signs of inflammation (rubor, calor, dolor, tumor,
functio laesa)
o DDx: SLE/RA/Septic arthritis/JRA (small joints,
primarily)
- Abdominal pain
o primary peritonitis
o can present as an acute abdomen; mistaken for
appendicitis
- Glomerulonephritis
HSP Nephritis and IgA Nephropathy have identical findings,
except that systemic findings are only found in HSP.

microscopic hematuria/proteinuria > isolated PATHOGENESIS

hematuria/proteinuria > combination
TREATMENT
- proper BP control
- fish oil
o with anti-inflammatory omega-3 FA
o decrease rate of renal progression
- immunosuppressive therapy with corticosteroids or more
intensive multidrug regimens (i.e. cyclophosphamide)
o beneficial in some patients
- remains unknown
- appear to be mediated by the formation of immune
complexes containing polymeric IgA1 within capillaries of
the skin, intestines, and glomerulus
DIAGNOSIS
- Non-specific: based on clinical findings
o gross hematuria: 20-30%
o isolated microscopic hematuria
o hematuria and proteinuria

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 o acute nephritic s/sx o roughening of capillary wall
o nephrotic s/sx o mechanical damage to RBC and subsequent lysis
o renal insufficiency o release of hemoglobin (toxic to the kidney)
- Specific o hemoglobinuria (tea-colored urine)
o renal manifestations occurring up to 12 weeks after o renal failure
initial presentation - Other contributing factors:
o hypercoagulability
URETERITIS § nephrotic syndrome
- uncommon urologic manifestation § Factor V Leiden
- loin pain and renal colic o hypovolemia
- children <5 years § septic shock
- may lead to ureteral stenosis and structures, causing § dehydration
hydronephrosis that requires surgical correction § nephrotic syndrome
o Hydonephrosis will destroy kidneys at whatever o intravascular sludging (polycythemia)
degree.
MANIFESTATIONS
TREATMENT - heralded by sudden onset gross hematuria and
- No controlled data unilateral/bilateral flank masses
- Uncontrolled studies: high potential value of high-dose - may also present with microscopic hematuria, flank pain,
steroids, tacrolimus, cytotoxic therapy (i.e. hypertension and oliguria
cyclophosphamide, azathioprine) in patients with - RVT is usually unilateral.
crescentic GN or sig. proteinuria. o hemoglobinuria damages kidney, but no failure
- Additional dipyridamole and/or heparin/warfarin may - Bilateral RVT causes acute renal injury and immediate ARF.
provide added benefit.
DIAGNOSIS
PROGNOSIS - suggested by the development of hematuria and flank
- generally favorable masses in patients positive for predisposing clinical factors
- Signs and symptoms may continue for several months, - most patients also have microangiopathic hemolytic
especially GN anemia (RBC lysis) and thrombocytopenia
- risk of chronic renal insufficiency is 2-5% - UTZ: marked enlargement
- BEST PROGNOSIS - isolated microscopic hematuria - Radionucleotide studies: little or no renal function in
- Highest risk of CHRONIC RENAL FAILURE affected kidneys
o both acute nephritic and nephrotic syndromes - Doppler Flow of IVC and renal vein confirm the diagnosis
- Contrast studies are avoided to minimize the risk of further
RENAL VENOUS THROMBOSIS vascular damage.
NEWBORNS AND - asphyxia
INFANTS - dehydration DIFFERENTIAL DIAGNOSIS
(+) risk factors - shock - Hemolytic-Uremic Syndrome
- sepsis o secondary to undercooked hamburgers; older
- infants born to mothers with DM children
OLDER CHILDREN - nephrotic syndrome (more common o (+) sudden onset gross hematuria
in adults) o (+) microangiopathic hemolytic anemia
- cyanotic heart disease o (+) thrombocytopenia
- inherited hypercoagulable states
- (+) Flank Masses
- exposure to angiographic contrast
o Hydronephrosis
agents
o Polycystic Kidney Disease
THROMBUS FORMATION o Wilm’s tumor
- mediated by endothelial cell injury resulting from hypoxia, o Renal abscess
endotoxin, or contrast media o Hematoma
o endothelial cell injury causes reparative
mechanisms TREATMENT OF PRIMARY CAUSE
o vasoconstriction (more severe in clean cut) - supportive care:
o platelet plug o correction of fluid and electrolyte imbalance

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 o treatment of renal insufficiency
- Anticoagulation or thrombolysis remain controversial
o streptokinase
o urokinase
o recombinant t-PA
o difficult in patients with sepsis and deranged
coagulation
- Surgical Thrombectomy - thrombosis of the IVC
- Nephrectomy
o children with severe HTN (kidneys non-functional)
refractory to antihypertensive medications
PROGNOSIS
- Perinatal mortality from RVT has decreased significantly
due to intensive support.
- Partial or complete renal atrophy is a common sequela of
RVT leading to renal insufficiency (early onset), renal
tubular dysfunction and systemic hypertension
- Recovery of renal function is common in children with RVT
due to nephrotic syndrome or cyanotic heart disease
- RVT during neonatal period requires follow-up for life
because of early onset hypertension.
URINARY TRACT INFECTION
- Can involve any age group
- Accounts for 30% of pediatric consultations
- Host defense mechanism versus bacterial virulence factors:
o increased virulence and decreased defines
o same virulence with decreased defense
- Considered as a manifestation of an underlying problem
- Never treat a single infection alone.
- Note for underlying causes; look for risk factors.
- UTI is the most common disease in the first year of life with
the male to female ratio of 2.8 – 5.4 : 1 (boys > girls)
o Urinary abnormalities especially Dilating
Nephropathies and Obstructive Neuropathies are
more common in males than in females (accounts
for the increased incidence of UTI in males during
the first 6 months of life)
- Beyond 1 – 2 years, there is a female preponderance with
a male: female ratio of 1:10
o In girls, the 1st UTI usually occurs by 5 y/o, which
peaks during infancy and toilet training
- Independent risk factors for recurrence are:
o 1st UTI at the age of <6 mons
o 3 -5 years old
o Vesicoureteral reflux during grades 3- 5
§ Vesicourethral reflux is the backflow of
urine from the urinary bladder
§ In grade 3 there is already dilation of urinary
tract which means patient already have
hydronephrosis
PEDIATRICS 3A: NEPHROLOGY A
Grade I - Reflux into nondilated ureter
Grade II - Reflux into renal pelvis and calyces without dilation
Grade III - Reflux with mild to moderate dilation and minimal
blunting of fornices
Grade IV - Reflux with moderate ureteral tortuosity and dilation
of pelvis and calyces
Grade V - Reflux with gross dilation of ureter, pelvis, and calyces,
loss of papillary impressions, and ureteral tortuosity
HOST FACTORS:
- constipation - directly related to UTI
- infrequent urination
- flushing mechanism of urine helps in getting rid of bact.
- associated with holding or postponing urination
- normal urination in neonates is 8-12x; voids q feeding
- immune system
- congenital/functional problems: may cause recurrent UTI
BACTERIAL VIRULENCE FACTORS:
- Ability to adapt
- Fimbrae
PATHOGENESIS
- Ascending infection
- Periurethral area contains bowel bacteria
- This is caused predominantly of E. coli in girls, and after the
first 6 months of life, Proteus in boys
- In older children, gram negative bacteria colonizes the
periurethral area and precedes the development of UTI
- The change from normal flora may be induced by a course
of a broad spectrum antibiotics causing an infection
o Patients taking broad spectrum antibiotics may also
involve and kill the normal flora that brings about
the rise of pathogenic organism that causes UTI
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 BACTERIAL VIRULENCE HOST RESPONSE TO UTI o malodorous urine
FACTORS - asymptomatic bacteriuria
E.coli strains express Innate host immune o (+) urine culture without manifestations of infection
surface fimbriae (P fimbriae) system o mostly in girls; mostly benign
Flagella mediated Cytokine production
motility CLINICAL PRESENTATION
Lipopolysaccharide Neutrophil recruitment - The most useful indicators of UTI in infants aged below 24
production to kill bacteria months are:
Capsular polysaccharide IL – 6 o Fever above 40 degrees
IL – 8 causes and increase in o Previous history of UTI
Hemolysins neutrophil migration and o Fever for more than 24 hours
activation resulting o Suprapubic tenderness
in pyuria
o Ill appearance
E.coli compete with host cells
o No other source of fever
for nutrients
including iron o Uncircumcised in boys
Aerobactin which is a high o Combined predictors of fever exceeding 39 degrees
affinity iron-binding C for more than 48 hours without another source of
protein. fever were more useful that individual findings.
“The occurrence of UTI can be affected mainly by interplay o The presence of abdominal pain, back pain, dysuria,
between the bacterial virulence factors and host defense frequency and new onset incontinence increased the
mechanisms. If the bacterial virulence factor overwhelms the host likelihood of a UTI in older children.
defense response, patient then will develop UTI.”
CLINICAL SYMPTOMS (Varies on the age group)
ETIOLOGIC AGENTS - Febrile children below 5 years old: (preschool – toddler)
- Predominant organisms are gram o Fever above 38 degrees
negative organisms (EKE) o Looking unwell
o E. coli >80% o Urinary symptoms
o Klebsiella pneumonia o Reduced fluid intake
o Enterobacter - Neonates:
- Proteus vulgaris : for uncircumcised boys o Lethargy
- S. saprophyticus: acute UTI for adolescent girls o Poor feeding
- E. coli is the most common pathogen even in adults o Jaundice
- Proteus sp. are common cause UTI in uncircumcised o Fever or no fever in combination of the
boys presentation above
- Staphylococcus saprophyticus is common cause in o UTI in neonates presents nonspecific clinical
asymptomatic bacteriuria in female adolescents (only symptoms and sometimes with similar
diagnosed with UTI secondary to urine culture with manifestation with sepsis
presence of Staph saprophyticus without any symptoms o Neonatal sepsis would present with:
at all) § Fever / no fever
§ Hypothermia / hyperthermia
BASIC FORMS OF UTI § Jaundice especially within first 24 hours is
- Pyelonephritis always interpreted as pathologic, but even if
o abdominal, back, or flank pain jaundice occurred after the first 24hrs and
o fever - may be the only manifestation at times the onset is very sudden will still be
o malaise considered as pathologic. (Physiologic
o nausea and vomiting Jaundice occurs in a slow cephalocaudal
o diarrhea (occasionally) manner
- cystitis o Sepsis are common because neonates are
o indicates bladder involvement considered to be immunocompromised population.
o dysuria They may have immunoglobulins and white cells,
§ discomfort at “terminal” phase of but they cannot respond adequately as compared
micturition to older children or adults.
o urgency, frequency, suprapubic pain, incontinence o Infection can easily spread in neonates.

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 § UTI can also cause sepsis to neonates colonies and the child is symptomatic, the child is
considered to have UTI
URINARY SAMPLE COLLECTION - In a bag sample (wee bag), if the urinalysis result is positive,
- “The diagnosis of UTI will start with Urinalysis. It is very the patient is symptomatic, and there is a single organism
important not just to get any urine sample, but to get a cultured with a colony count >100,00, there is a presumed
quality urine sample.” UTI
o Clean voided samples (common) - “In clinical practice , even at least 10,000 CFU/mL of a
o Catheterized sample single bacterial specie provided patients is symptomatic”
o Suprapubic sample
CRITERIA FOR THE DIAGNOSIS OF UTI BY URINE CULTURE
o Dipstick testing of urine for WBC esterase and nitrite
or urinary microscopy for pyuria or bacteria cannot (GOLD STANDARD) BASED ON COLONY COUNT
replace urine culture for the diagnosis of UTI. Method of Collection Colony Count Probability of Infection
“Suprapubic and catheterized samples are considered invasive Suprapubic aspirate Any number >99%
and are reserved for patients who have difficulty in obtaining a Catheter ≥10,000 95%
quality clean catch sample. Also for patients with anatomical Clean void ≥100,000
problems that may hinder in getting a quality clean catch like boy 1 specimen infection unlikely
patients with imperforate anus that also have rectovaginal fistula girl 1 specimen 80%
2 specimens 90%
wherein feces exit to the vagina.”

What may cause a false negative culture:

TEST SENSITIVITY SPECIFICITY
- Already had an antibiotic administration
WBC ESTERASE 83% 78% - A double voided urine sample
NITRITE 53% 98% - diluted urine
WBC ESTERASE 93% 72%
AND
RISK FACTORS
NITRITE
- CONGENITAL FUNCTIONAL PROBLEMS
MICROSCOPY
WBC >5 / hpf 73% 81% o Important concern for these may cause recurrent
Bacteria 81% 83% UTI
(+) WBC ESTERASE, 99.8% 70% - IMMUNE SYSTEM OF THE PATIENT
NITRITE, MICROSCOPY o Could be due to increase virulence and decrease in
the defense mechanism of the patient
- “In the Philippines the cutoff considered as significant in - CIRCUMCISION
diagnosing UTI is presence of WBC >5/hpf. It is only o According to Singh-Grewa et al, the risk of
considered significant value to consider UTI, it does not complications outweighed the benefits in boys
always mean that patient already have UTI.” without UTI, but in boys with previous UTI or high
- “Sensitivity increases as the tests are combined together.” grade VUR (III- V), the benefits outweighed the risks.
- “Specificity of 70%: if all of the tests are negative in 10 o The American urological association (AUA) states
patients, only 7patients are sure to be negative while the 3 that the circumcision of the male infant with VUR
patients are not sure to be negative to have UTI.” may be considered based on an increased risk of UTI
- “4 parameter test used by old hospitals / clinics in in boys who are not circumcised.
Philippines: pH, Specific gravity, Protein and Sugar” - BLADDER BOWEL DYSFUNCTION
- “Even if the sensitivity of these tests combined: 99.8%, it o The risk of febrile UTI in children with VUR on
cannot replace URINE CULTURE (gold standard) in continuous antibiotic prophylaxis is greater in
diagnosing UTI.” patients with BBD compared with those without
BBD
DIAGNOSIS BASED ON URINE CULTURE o RISK FACTORS
- Freshly voided urine sample: >100,000 CFU / mL of a single § Daytime urinary incontinence
bacterial species § Squatting and other holding maneuvers
- Catheter specimen: >104 CFU/mL (Sphincter control, children seating on heel,
- Suprapubic aspiration: any bacterial growth etc.)
- If the culture shows >50,000 colonies of a single pathogen § Prolonged or fractionated voiding
(suprapubic / catheter sample), or if there are 10,000 § Increased residual volumes (pre vs post-
voiding bladder US)

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 § Constipation – directly related to UTI - Most sensitive investigation for acute and chronic kidney
§ Fecal soiling damage
o INTERVENTION - Cannot differentiate damage due to UTI and congenital
§ Increasing fluid intake causes
§ Regular or timed voiding (e.g. every 3 hours
even if they don’t feel urgency to void) KUB
§ Relaxation measures to avoid holding - Kidney, urinary bladder
maneuvers - Pre and post void bladder ultrasound
§ Prevention and treatment of constipation - First renal imaging study performed for a diagnosed case of
§ Use of bladder and bowel diaries to assess UTI
progress - Normal kidney is vascular, same echogenicity with liver
- Kidney whiter than liver, classified as hyperechoic, and
IMAGING STUDIES indicates renal parenchymal disease
- “Renal imaging to localize renal infection and to see if there
are urinary abnormalities that could increase the risk for
recurrent febrile UTI.”
- OBJECTIVE
o To detect: Obstructive lesions, VUR, Kidney damage
- INDICATIONS
o Acute pyelonephritis
o Bacteriuria before 1 years of age
o Hypertension VCUG
o Abdominal mass - Voiding Cystourethrogram
o Decreased renal concentrating ability - High risk patients
o Recurrent cystitis (boys) - Reference standard for identifying VUR
o Covert bacteruria - Provides information on the bladder and urethra
o Posterior midline anomaly - For patients with atypical features (abnormalities: masses,
§ functional obstruction dimples in sacral area)
• Lumbosacral meningocele which - For Reflux
directly affects the function of the
urinary bladder RADIOLOGIC IMAGING OF THE GUT
- Radio-type imaging DMSA Scan
detects:
o scars after pyelonephritis
o renal agenesis
o ectopic kidney
- Static renal exam
- Specific to the CORTEX
- Picture: Loss of superior pole of
left kidney; loss of function; cold
nodules/scarring

CONTROVERSIES SURROUNDING RENAL IMAGING

- Children with VUT have 1.5 x damage seen in DMSA
ULTRASOUND - Half of children without VUT also have changes
- Non invasive - Systematic review of 13 studies showed that DMSA is a
- Identify structural abnormalities: poor predictor of dilating VUR
o Obstruction - VCUG and DMSA scans are associated with significant
o Differences in kidney size radiation exposure
o Kidney damage

DMSA
- Sensitivity of 86% and specificity of 91% in identifying acute
parenchymal injury following UTI

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 TOP TO BOTTOM VS. RETROGRADE STUDIES FIRST o Increase level of Procalcitonin, CRP, White blood cell
- NATIONAL INSTITUTE OF HEALTH AND CARE EXCELLENCE count
(NICE) SENSITIVITY SPECIFICITY CUT OFF
o Uncomplicated first UTI of children over 6 months PROCALCITONIN 71% 72% 0.5 ng/mL
require no investigation CRP 87% 41% 20 mg/L
- AAP AND ISPN GUIDELINES WBC 63% 55% 15,000/mm3
o All infants 2 -24 months with febrile UTIs should “Even if they are said to be indicators of UTI. In reality they cannot
undergo ultrasound differentiate Upper from Lower not unless coupled with a postive
- All guidelines do not recommend routine VCUG and DMSA DMSA”
unless:
o Ultrasound is abnormal LOWER TRACT INFECTION
o Child is seriously ill - From urinary bladder and down
o Fails to respond rapidly to antibiotics - Considered uncomplicated infection
o Recurrent infection UPPER TRACT INFECTION:
- From ureter to kidneys
- Considered as complicated infection

TREATMENT
- Risk of kidney damage on DMSA scan 6 -12 mons after UTI
shows no significant difference between oral antibiotics for
No MAG 3 No workup 10-14 days vs IV meds for 3-4 days followed by oral
(MR antibiotics vs IV antibiotics for 7-14 days. (Not included in
up the study are 1-3 months old neonates)
- Majority of children may be treated with oral antibiotics or
short course IV antibiotics followed by oral antibiotics
- “The determinant in giving specific treatment is the patient.
If the patient is still active and strong, give oral antibiotics.
If the patient is suffering already like pyelonephritis and is
ill- looking, give IV for short course followed by oral
- Retrograde: start with VCUG first
o If (+) Reflux: do DMSA antibiotics or give It entirely for 7 -14 days. (only covers
patients >3months of age)
o If Normal: No work up
- 1-3months of age: a continuous antibiotic through IV is
o If (+) Hydronephrosis): Do MAG-3 Lasix, Renogram
used to treat UTI. “
(MR Urogram)
- Top to Bottom: Starts from a renal scan (DMSA) proceed to
CONTINUOUS ANTIBIOTIC AS PROPHYLAXIS
other investigation depending on the result of the scan:
- RCT’s found no difference in the efficacy of antibiotics in
o If (+) Cortical defect(pyelonephritis): proceed to
VCUG preventing UTI between children with and without VUR or
o If Normal no work up done but if recurred, febrile between mild and severe VUR
- Done for the last 50 years
UTI do VCUG
- For patients Identified to be:
o If (+) Central photopenia (hydronephrosis): do
o Those with recurrent febrile episodes
sonogram
o Those with high degree of VUR
- Antibiotics used for prophylaxis:
LOCALIZATION OF UTI
- Standard for acute pyelonephritis is o Any antibiotic, popularly used are 1st gen ceph,
acute parenchymal damage on DMSA scan trim-sulfa, nitrofurantoin
- Increased levels of:
WHICH ANTIBIOTICS TO USE?
o Procalcitonin
- On the basis of resistance patterns:
o CRP
o >50% are resistant to ampicillin
o WBC
- Metanalysis of 18 studies of children with febrile UTI: o 30% resistant to trimethroprim and first gen
cephalosporins
o 61% positive for DMSA

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 o Amoxicillin-clavulanate and to third gen
cephalosporins are also increasing due to ESBL
producing E.coli
Step 1. Identify organism
Step 2. Give empirical treatment based on the most common
pathogen for the age group
If E. coli..and uncomplicated.. amoxicillin-clavulanate as primary
empirical treatment
OTHER THERAPIES
- Cranberry
o Inhibits the p. fimbriae of ecoli preventing it from
adhering to uroepithelial cells, therefore E. coli can
be easily flushed out from the urinary tract
- Probiotics
o Invitro studies shows bactericidal effects
o RCTs: no significant data that proves its advantages
against UTI
- Vaccines
o In adults: immuno stimulants are beneficial
o In pediatrics: no study to support
WILM’S TUMOR (NEPHROBLASTOMA)
- Complex mixed embryonal neoplasm of the kidney
composed of;
o Blastema
o Epithelia
o Stroma
- 8 cases/million children <15 years of age
- Peak: 2-5 years of age
- Second most common malignant abdominal tumor in
childhood
- Abdominal masses are considered a medical emergency.
- May arise in one or both kidneys; one side may be bigger
than the other. The incidence of a bilateral Wilms is 7%.
- May be associated with the following:
o Hemihypertrophy - one side is bigger, very obvious
o Aniridia - absence of iris, unilateral or bilateral
o Other congenital anomalies, usually of GUT
o variety of syndromes
- Majority are sporadic
- 1-2% are familial, AD
o Familial cases are associated with diagnosis at an
earlier age
o increased frequency of bilateral disease
o congenital absences are usually absent
o not associated with Wilms tumor gene (WT1)

GENITOURINARY ANOMALIES (MOST COMMONLY ASSOCIATED)

- hypoplasia (small kidney, few glomeruli)
- fusion (horseshoe kidney) and ectopia (not in the renal
fossa), 2 kidneys on the same side
- duplication of the collecting systems (hydronephrosis at the
upper portion of the system)
- hypospadias
o mild: meatus displaced at apex
o moderate: at the middle
o severe: at the perianal area
- cryptorchidism

ASSOCIATED SYNDROMES
- WAGR syndrome
- Denys-Drash syndrome
- Beckwith-Wiedemann syndrome
- Pearlman syndrome
- Sotos syndrome
- Neurofibromatosis (von Recklinghausen disease)
- von Willebrand disease

CLINICAL MANIFESTATIONS
- abdominal mass - approached as malignant mass
- smooth, firm
- occasionally cross the midline
- abdominal pain, vomiting
- hematuria
- hypertension

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 HISTOLOGY
FAVORABLE UNFAVORABLE
- conventional form - markedly large nuclei
characterized by - hyperchromatism and
blastema, epithelia and multipolar figures of
stromal elements nuclei
- devoid of ectopia or - areas of anaplasia may be
anaplasia focal or diffuse; predict
high rates of tumor
relapse and death
- clear cell sarcoma is a
subtype of the
unfavorable form and
usually metastasizes to
the bone
OTHER DISEASES:
- BENIGN FAMILIAL HEMATURIA
o Verify if hematuria present also in immediate or
distant family members
o Work up minimally then observe (Urinalysis, Rnela
function test and UTZ) then follow up
o If there is no progression, no need for renal biopsy
- ALPORT’S SYNDROME
o Familial
o initially a seemingly benign micro hematuria
o after several years: proteinuria, renal deterioration
o In family history: one relative would have
progressive renal problems ending up in dialysis
o associated sensorineural deafness

DIAGNOSIS CHEMOTHERAPY GUIDELINES

- Abdominal mass - urgent nature of the condition S1, S2 with - Vincristine
- complete PE, CBC favorable histology - Dactinomycin
- Liver and Kidney FT’s S3 with favorable - Radiation in tumor
- Specific tumor markers histology bed
- Flat plate of the abdomen
- Ultrasonography - often used
- CT/MRI - Radiation to sites
- Chest X-ray: detection of metastasis, useful for pre-op S4 with favorable - Vincristine
histology - Dactinomycin of known disease,
- Doxorubicin particularly the
- tumor limited to kidney; completely confined lungs
S1 (NO - capsule intact; no tumor rupture; no residual
RESIDUAL) tumor apparent beyond margins of excision - surgical resection
S4 with tumor in may be
- tumor extends beyond kidney but completely
the liver considered, as
excised
S2 (NO - regional extension of tumor; vessel infiltration; opposed to
radiation
RESIDUAL) tumor biopsied or local spillage of tumor
confined to the flank S4, resistant
- no residual tumor apparent at or beyond tumors that w/ - Consider surgical resection and alternate
margins of excision chemo or radiation or investigational chemotherapy and
failure; recurring alternate or investigational chemotherapy
S3 WITH - residual non-hematogenous tumor confined to tumors
RESIDUAL P the abdomen
TUMOR - LN involved of hilus, periaortic chains, or beyond Unfavorable - Vincristine - Radiation to
SURGERY - diffuse peritoneal contamination by tumor histology - Dactinomycin tumor bed and
spillage; peritoneal implants of tumor; tumor - Doxorubicin sites of
extends beyond surgical margins microscopically - Cyclophos- established
or macroscopically phamide metastasis
- tumor not completely removable d/t local - More aggressive
infiltration into vital structures e.g. Aorta treatment
S4 - Distant metz, deposits beyond S3 (e.g. lung, liver, Wilms tumor not - Chemotherapy is administered
bone, brain) operable - Diagnosis established by percutaneous
needle biopsy
S5 - Bilateral renal involvement at diagnosis
Bilateral Wilms - Chemo identical - Surgical
tumor to that extirpation after
TREATMENT employed in chemo
inoperable
- Surgery tumors utilized
- Patency of the IVC should be established prior to resection
- IVC not patent: chemotherapy should be administered

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 PROGNOSTIC FACTORS NEPHRITIS) Least presence of mild to moderate
- Major prognostic factors are tumor size, stage and common mesangial proliferation
histology
- Prognosis is worse with: SLE GN PATHOLOGY
o large tumor (>500g) - Clinical manifestations are mediated by immune complexes
o advanced stage (S3, S4) - Aberrations in both B - and T-cell function
o unfavorable histological type - WHO classification based on light microscopy +
- Wilms tumor constitutes a paradigm of successful immunofluorescence + electron microscopy features
multidisciplinary treatment; more than 60% of patients o Transformation from one class to another is
with all stages generally survive common
- Stages I through III have a cure rate varying from 88-98%. o Likely to occur in inadequately treated patients

GLOMERULONEPHRITIS ASSOCIATED WITH SYSTEMIC LUPUS CLINICAL MANIFESTATIONS:

ERTHEMATOSUS (GN SLE) - Clinical evidence in 30 -70% of children
- Characterized by fever, weight loss, rash, hematologic o Kidney disease is one of the most common features
abnormalities, arthritis, and involvement in the heart, of SLE in childhood, may even be the only one
lungs CNS and kidneys - Milder forms (all class II, some class III)
- Majority are adolescent females o Hematuria
o Normal renal function
WHO CLASSIFICATION o Proteinuria of <1g/24 hours
CLASS I NEPHRITIS No histologic abnormality - Some class II, all class IV
CLASS II NEPHRITIS Glomeruli with mesangial deposits o Hematuria and proteinuria
(MESANGIAL LUPUS with Ig and Complement o Reduced renal function
NEPHRITIS) o Nephrotic syndrome
CLASS II A Mild mesangial hypercellularity o Acute renal failure
- Class IV can rarely have normal urinalysis
CLASS II B Moderate mesangial
- Class V
hypercellularity and increase matrix
o Nephrotic Syndrome
CLASS III NEPHRITIS Almost all glomeruli
(FOCAL SEGEMENTAL - Mesangial deposits
DIAGNOSIS
LUPUS - Subendothelial deposits
- Circulating ANAs suggestive
GLOMERULONEPHRITIS) between endothelial cells
- Ab to naïve dsDNA confirmatory
and glomerular basement
- C3, C4 depressed
membrane
- Renal biopsy if no clear correlation between cli nical
Occasional
manifestations and severity of renal involvement
- Capillary wall necrosis,
- Results guide immunosuppressive treatment
crescent formation, and
sclerosis
TREATMENT
CLASS IV NEPHRITIS ALL GLOMERULI
- Pediatric specialist required
(DIFFUSE - Significant mesangial
- Immunosuppressive therapy -> establish clinical and
PROLIFERATIVE LUPUS deposits
serologic remission
NEPHRITIS) most - Subendothelial deposits of Ig
o Normalization of anti -DNA, C3 and C4 levels
common and most and complement
- Initial : PREDNISONE at 1-2 mg/ kg/ day in 2 -3 divided
severe - Mesangial proliferation
doses
FREQUENTLY
o Tapered over 4-6 months, 4-6 week after remission
- Capillary walls thickened,
- More severe forms (III and IV) 6-month IV
secondary to subendothelial
o Cyclophosphamide at 500 -1000 mg/ m2
deposits (WIRE LOOP LESION)
o Followed by every 3 months for 18 months
often necrosis, crescent
formation, and scarring - Class I or II steroid spari ng agent Azathioprine at 1.5
CLASS V NEPHRITIS Resembles idiopathic membranous - 2.0 mg/ kg OD
(MEMBRANOUS LUPUS glomerulopathy, except for - Mild Mycophenolate mofetil
- Refractory Class IV Riuximab, a chimeruc monoclonal Ab
specific for human CD20

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 PROGNOSIS PATHOLOGY
- Aggressive immunotherapy -> improved prognosis - Initial glomerular changes due to subendothelial and
- Renal survival without dialysis in 80% after 10years mesangial deposition of granular, amorphous, material of
- Highest risk for ESRD - diffuse proliferative class IV unknown origin
- Risks of treatment o Thickening of capillary walls
o Chronic immunosuppressive treatment o Narrowing of capillary lumens
o Chronic steroid treatment: osteoporosis, obesity, o Widening of mesangium
HPN, DN - Fibrin thrombi - in glomerular capillaries/ arterioles ->
o Cyclophosphamide (>20g): high risk of malignancy Cortical Necrosis
of infertility - Severe partial or total sclerosis, - ischemia, concentric
intimal proliferation -> vascular occlusion
HEMOLYTIC UREMIC SYNDROME (HUS)
- Most common cause of acute RF in young children PATHOGENESIS
- Classic triad - Endothelial cell injury
o Microangiopathic hemolytic anemia - Localized clotting in the kidney capillaries/ arterioles
o Thrombocytopenia o DIC is unusual
o Uremia o Low C3 in non-diarrheal forms
- Features common to TIP except latter tends to occur in - RBC damage à microangiopathic anemia
young adult women as relapsing illness with fever, serious - Intrarenal and diffuse microvascular platelet
CNS involvement and thrombocytopenia adhesion/ damage à Thrombocytopenia

ETIOLOGY CLINICAL MANIFESTATION

TYPICAL - Acute enteritis with diarrhea caused - Most common in children <4 years old
(Post- by Shiga - like verotoxin -producin E. coli - Onset usually preceded by gastroenteritis characterized by
diarrheal) 0157:H7 80% fever, vomiting, abdominal pain, and diarrhea (watery à
HUS - Shigella and less commonly bloody)
o Salmonella, campylobacter, o Less common: URTI
Streptococcus pneumonia, Bartonella - 5-10 days later: sudden onset of pal lor, irritability,
o Coxsackie, echovirus, influenza, weakness, lethargy, oliguria
varicella, HIV, EBV - PE: dehydration, edema, petechiae, hepatosplenomegaly
ATYPICAL - UTI due to Shiga toxin -producing and marked irritability
HUS - E. Coli
DIAGNOSIS AND DIFFERENTIALS
- Post-infectious outside GIT
- Clinical findings - always consider HUS in pediatric ARF
(Streptococcis pneumonia)
o Differentials: SLE and malignant hypertensio n,
- Oral contraceptives, mitomycine or
cyclosporine, gancyclovir, crack cocaine, bilateral RVT (diff by Doppler)
quinine
- Exposure to pyran copolymer CBC
- Hgb: 5-9g/ dL
- Familial occurrence no diarrhea,
AR, or AD o High plasma hgb, but low plasma haptoblobin
o Mutation in complement - PBS: helmet cells, burr cells, fragmented RBCs
component H - Retic: moderately elevated
o Complete deficiency of Von - (-) Coombs test
Willebrand factor - Significant leukocytosis: usually > 3-,000/ mm3
o metalloprotease and - Thrombocytopenia (90%): 20,000 100,000/ mm3
membrane cofactor protein - Normal PTT and PT (no vitamin K deficiency)
- Rare Association: SLE, malignant
ACUTE RENAL INJURY
hypertension, preeclampsia,
postpartum renal failure, and radiation Varies: mild RI to acute oliguric or anuric RF requiring
nephritis dialysis
o Elevated creatinine level
Urinalysis surprisingly mild
o Low-grade microscopic hematuria and proteinuria

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 IMAGING TUBULOINTERSTITIAL NEPHRITIS (TIN)
Barium contrast studies: colonic spasms, transient early Characterized by tubulointerstitial inflammation and
filling defects damage with relative sparing of glomeruli and vessels
Radio: colitis (thumb -printing) Acute and chronic forms: Primary or Systemic/Secondary

CASE CLASSIFICATION (CDC) ACUTE TIN

CONFIRMED
Hallmarks: lymphocytic infiltration of tubulointerstitium,
o Acute illness diagnosis as HUS or TTP meeting lab
tubular edema, varying degrees of tubular damage
criteria with history of acute or bloody diarrhea in
Eosinophils (drug -induced), granulomas
past 3 weeks or
T cell-med immune mechanism, unknown pathology

PROBABLE
CLINICAL MANIFESTATIONS
o Meeting laboratory criteria with no clear history of
Classic Fever, Rash, arthralgia, + increased serum creatinine
acute or bloody diarrhea in past 3 weeks OR
o Rash: maculopapular to urticarial, often transient
o Onset with in 3 weeks after acute or bloody diarrhea
Nonspecific: N/V, fatigue, weight loss
ad meets lab criteria except microangiopathy
Flank pain (stretched renal capsule)
unconfirmed
30-40% non-oliguric
Microscopic hematuria
COMPLICATIONS
o Sig H or P is uncommon - except w/ NSAIDs
Anemia, acidosis, hyperkalemia, fluid overload, heart
Urinalysis - WBC casts, granular or hyaline ca sts, but NO
failure, hypertension, and uremia
RBC casts
Extra-renal (~life-threatening)
o Eosinophils - not sensitive or specific
o CNS: irritability, seizures, infarcts of BG and CC,
cortical blindness, coma
DIAGNOSIS
o GIT: Ischemic or inflammatory colitis, intestinal
Clinical and laboratory
perforation, intussusception and hepatitis
Careful history of timing especially with respect to drug
o Pancreas: Focal necrosis -> acute pancreatitis,
exposure (usually 1-2 weeks after)
glucose intolerance, insulin – dependent DM, High
RUS: not diagnostic but may see echogenic, enlarged
lipase
kidneys
o Heart: Pericarditis, myocardial dysfunction,
Removal of an agent with improvement: highly suggestive
arrhythmias
Severe, rapidly deteriorating - do biopsy
o Other: Skin necrosis, parotitis, adrenal dysfunction,
rhabdomyolysis
TREATMENT AND PROGNOSIS
Supportive, address complications of ARF (hyperK or
PROGNOSIS AND TREATMENT
volume overload)
Supportive care
Corticosteroids
o Fluid and electrolytes: Aggressive vutrition
Best prognosis: rapid improvement w/ o treatment
o Control Hypertension: Early dialysis
Guarded prolonged RI
Avoid antibiotics (Higher HUS risk)
Anti-thrombotic treatment, Plasmapheresis: no proven
CHRONIC TIN
benefit
Diarrheal 90% survive: 12% ESRD or death In children, commonly due to underlying congenital renal
Worst Prognosis disease: obstructive uropathy or vesicoureteral reflux or
o CNS symptoms antimicrobials
o WBC: >20,000, ischemic colitis, hypertension Idiopathic: more common in adults
Transplant does not guarantee no recurrence Seen in all forms of progressive renal disease
F-U required: some complications manifest 20 years later Severity is most important factor in progression to ESRD
Undefined pathophysiology, maybe immune mediated

JUVENILE NEPHRONOPHTHISIS (JN)/MEDULLARY CYSTIC KIDNEY

DISEASE COMPLEX (MCKD)
Group of inherited cystic renal diseases that share common
histo phenotype of chronic TIN

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 JUVENILE NEPHROPHTHISIS (JN)
Rare AR (however, in Europe cause 10-2% of ESRD)
Polyuria, growth failure, “unexplained” anemia and CRF in
late childhood or adolescence
Variants
o Senior-Loken syndrome (retinitis pigmentosa)
o Joubert syndrome
o Oculomotor apraxia type Cogan

MEDULLARY CYSTIC KIDNEY DISEASE COMPLEX (MCKD)

AD typically presents in adulthood

TUBULOINTERSTITIAL NEPHRITIS WITH UVEITIS

Rare autoimmune syndrome of chronic TIN + anterior
uveitis + bone marrow granulomas
Usually adolescent females

CHRONIC TIN PATHOLOGY

Kidneys - pale and small for age
Micro: tubular atrophy and drop out with interstitial
fibrosis and a patchy lymphocytic interstitial inflammation
JN: characteristic small cysts in corticomedullary region
Primary CTIN: glomeruli relatively spared until late disease

CHRONIC TIN CLINICAL MANIFESTATIONS

Often non -specific, may have s/ sx of chronic renal
insufficiency
Fatigue, growth failure, polyuria, polydipsia, and enuresis
Anemia is common (JN)
Significant hypertension: tubular damage = salt wasting

CHRONIC TIN DIAGNOSIS

Signs and Symptoms of renal tubular damage : polyuria,
increase creatinine + history suggesting chronic disease
(long -standing enuresis or anemia)
RUS: evidence of chronicity, corticomedullary cysts (JN) or
obstructive uropathy
o Vesicocystourethrogram: VUR or bladder
abnormality
JN: molecular diagnosis
Unclear - do biopsy if not too advanced

CHRONIC TIN TREATMENT AND PROGNOSIS

- Fluids and electrolytes
- Avoid nephrotoxic agents
- Obstructive uropathy salt supplement, K + binding resin
(Kayexalate à watch out for arrhythmia)
- Antibiotic prophylaxis
- Variable prognosis, ~ESRD (*JN)

USE AT YOUR OWN RISK! NO PROOFREADING WAS DONE!

Notes from Bahaghari Trans, Additional Trans, Cruz and Mari
Trans, MRA Trans

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