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CASE I - 4-year-old male with anasarca for 2 weeks

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Q1. Five Most Common Causes of Anasarca in Children (5 marks)

1. Nephrotic syndrome - most common renal cause; massive proteinuria leads to hypoalbuminemia and subsequent generalized edema
2. Congestive cardiac failure - right-sided failure causes systemic venous hypertension and edema
3. Chronic liver disease / cirrhosis - reduced albumin synthesis + portal hypertension
4. Protein-energy malnutrition (kwashiorkor) - severe hypoalbuminemia
5. Acute glomerulonephritis (nephritic syndrome) - sodium and water retention

The clinical clue in this case - face-first onset, worse in morning, normal BP, no hematuria - strongly points to nephrotic syndrome.

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Q2. Differentiate Nephritic Syndrome from Nephrotic Syndrome (5 marks)

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Q3. Nephrotic Range Proteinuria and Diagnosis of Nephrotic Syndrome (2+3 = 5 marks)

Nephrotic Range Proteinuria:

• In children: Urine protein >40 mg/m²/hour, OR urine protein:creatinine ratio (uPCR) >2.0 mg/mg (>200 mg/mmol), OR 3+ to 4+ protein on urine dipstick
• In adults: >3.5 g/day (or >3.5 g/1.73 m²/day)

Diagnosis of Nephrotic Syndrome requires ALL of the following:

1. Massive proteinuria - uPCR >2.0 or dipstick 3-4+ on 3 consecutive days (or >40 mg/m²/hr)
2. Hypoalbuminemia - serum albumin <2.5 g/dL (<25 g/L)
3. Edema - pitting edema (periorbital, pedal, ascites, anasarca)
4. Hyperlipidemia - elevated total cholesterol, LDL, triglycerides; low HDL

The tetrad: Massive Proteinuria + Hypoalbuminemia + Edema + Hyperlipidemia

• Urine: 3-4+ protein, dipstick/spot uPCR >2.0; microscopy (may show lipid bodies/oval fat bodies)
• Serum albumin <2.5 g/dL
• Elevated cholesterol and triglycerides
• Normal complement C3/C4 (in MCNS - the most common cause)
• Normal BUN/creatinine (initially)
• 24-hour urine protein or spot uPCR confirms nephrotic range

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Q4. Classification of Nephrotic Syndrome by Response to Steroid Therapy (3 marks)

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Q5. Steroid Prescription for a 15 kg Child (2 marks)

• Prednisolone 2 mg/kg/day (maximum 60 mg/day)
• For 15 kg child: 2 × 15 = 30 mg/day as a single morning dose
• Duration: 4-6 weeks (until urine protein is negative for 3 consecutive days, then continue to complete 4-6 weeks)

• Prednisolone 1.5 mg/kg on alternate days (or 40 mg/m²)
• For 15 kg child: ~22.5 mg on alternate days (round to 20-22.5 mg on alternate days)
• Duration: 4-6 weeks, then stop

Tab. Prednisolone 5 mg Give 6 tablets (30 mg) once daily in the morning for 6 weeks Then give 4-5 tablets (20-22.5 mg) on alternate mornings for 6 weeks (Total course ~12 weeks)

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CASE III - 4-year-old with swelling for 1 month, frothy urine, BP 90/60

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Q1. Most Probable Cause of Swelling (2 marks)

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Q2. Differential Diagnosis of Anasarca (2 marks)

1. Nephrotic syndrome (most likely - renal cause)
2. Congestive cardiac failure (JVP raised, cardiomegaly, abnormal CVS - excluded here as CVS is normal)
3. Cirrhosis/chronic liver disease (jaundice, hepatomegaly, stigmata - excluded: no jaundice)
4. Protein-energy malnutrition (kwashiorkor) (nutritional history)
5. Acute nephritic syndrome / GN (hematuria, hypertension - absent here)
6. Hypothyroidism (myxedema - non-pitting)
7. Allergic/angioedema (transient, urticaria)

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Q3. Investigations and Expected Findings (4 marks)

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Q4. Treatment of Nephrotic Syndrome (4 marks)

• Prednisolone 2 mg/kg/day (max 60 mg/day) orally for 6 weeks - induction
• Then 1.5 mg/kg on alternate days for 6 weeks - tapering
• 95% of MCNS achieves remission

• Salt restriction (low-sodium diet, <1-2 g/day) to reduce edema
• Fluid restriction only if severe hyponatremia
• Diuretics (furosemide 1-2 mg/kg/day) for massive/symptomatic edema; use cautiously as can precipitate hypovolemia
• Albumin infusions (20% salt-poor albumin 1 g/kg) only for severe symptomatic hypovolemia or refractory edema
• Protein intake: Normal for age; do NOT restrict dietary protein

• Usually resolves with remission; statins considered if prolonged

• Daily first-morning urine dipstick for proteinuria at home
• Monitor BP, weight, urine output, edema

• Prednisolone 2 mg/kg/day until 3 consecutive urine protein-negative days, then 1.5 mg/kg on alternate days for 4 weeks

• Cyclophosphamide, levamisole, mycophenolate mofetil (MMF), calcineurin inhibitors (tacrolimus, cyclosporine), rituximab

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Q5. Common Complications of Nephrotic Syndrome (3 marks)

• Spontaneous bacterial peritonitis (SBP) - due to loss of immunoglobulins in urine; organisms: Streptococcus pneumoniae, E. coli
• Other: cellulitis, pneumonia, septicemia
• Patients are functionally hypogammaglobulinemic and opsonin-deficient

• Deep vein thrombosis, pulmonary embolism, renal vein thrombosis, cerebral venous sinus thrombosis (CVST)
• Due to: loss of anticoagulant proteins (antithrombin III, protein C & S), increased procoagulant factors, hemoconcentration, and thrombocytosis
• Clinically relevant: In the scenario where child developed monoparesis and altered sensorium on Day 5, the likely cause is cerebral venous sinus thrombosis (CVST)

• Due to low oncotic pressure (leaky edema) + aggressive diuretic use
• Presents with abdominal pain, tachycardia, cold peripheries

• From hypovolemia, thrombosis, or sepsis

• Dilutional hyponatremia, hypocalcemia (loss of vitamin D-binding protein)

• Cushingoid changes, growth retardation, cataracts, hypertension, osteoporosis, glucose intolerance, behavioral changes

• Accelerated atherosclerosis risk in long-term

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CASE III (continued) - Q19-Q22

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Q19. Likely Cause of Altered Sensorium + Monoparesis on Day 5 (2 marks)

• Loss of anticoagulants (antithrombin III, protein C, protein S) in urine
• Increased synthesis of procoagulant factors (fibrinogen, factors V, VIII)
• Hemoconcentration from hypoalbuminemia + diuretic use
• Thrombocytosis

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Q20. Possible Causes of New Onset Swelling after Discharge (2 marks)

1. Relapse of nephrotic syndrome - most common; relapse rate ~60-70% of children with MCNS; often triggered by upper respiratory infection
2. Steroid taper-related relapse - relapse during steroid tapering = steroid-dependent NS
3. Inadequate treatment duration - early discontinuation of steroids
4. Secondary nephrotic syndrome - e.g., underlying lupus nephritis (especially given the context of hypertension at next visit and persistent proteinuria)
5. Intercurrent infection - URTI is the most common relapse trigger

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Q21. Would You Proceed to Renal Biopsy? Explain with Reason (3 marks)

• Child is now hypertensive with trace protein (not full nephrotic range)
• This changes the picture - could suggest a different underlying pathology (e.g., focal segmental glomerulosclerosis, lupus nephritis, or another GN)

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Q22. Indications for Renal Biopsy in Nephrotic Syndrome (5 marks)

1. Age <12 months or >12 years at presentation (unusual ages for MCNS)
2. Macroscopic hematuria (gross blood in urine, not just microscopic)
3. Steroid-resistant nephrotic syndrome (SRNS) - failure to achieve remission after 4-8 weeks of adequate steroid therapy
4. Persistent renal insufficiency / elevated creatinine for >1-2 weeks not explained by hypovolemia
5. Low complement (C3/C4) levels - suggests post-infectious GN, MPGN, lupus nephritis
6. Systemic or syndromic features suggesting secondary cause - e.g., SLE, HSP, diabetes, drugs, positive ANA, butterfly rash
7. Frequently relapsing or steroid-dependent NS - before initiating steroid-sparing agents like calcineurin inhibitors or cyclophosphamide (to confirm histology and guide therapy)
8. Suspicion of familial/genetic nephrotic syndrome - for appropriate management planning
9. Unusual presentations - e.g., extreme hypertension, rapid deterioration of renal function
10. Failure to respond to second-line agents (CNI-resistant SRNS)

Key point: Empirical steroid therapy without biopsy is the standard for a child aged 1-12 years with typical first-episode nephrotic syndrome (periorbital/generalized edema, massive proteinuria, normal BP, no hematuria, normal complement).

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• Comprehensive Clinical Nephrology, 7th Ed (Table 18.2; pp. 265-266)
• Harriet Lane Handbook, 23rd Ed (pp. 703-705)
• Brenner & Rector's The Kidney (pp. 233-252)
• ISKDC Criteria / KDIGO 2021 Guidelines for Nephrotic Syndrome in Children