Diagnosis: Nephrotic Syndrome - Most Likely Minimal Change Disease (MCD)

Why This Diagnosis?

Classic Nephrotic Syndrome Features

Why Minimal Change Disease?

• MCD is the most common cause of nephrotic syndrome in children, especially between ages 1-7 years (though extends to school age)
• The child is vitally stable and active - renal function is usually preserved in MCD
• The glomeruli appear histologically normal on light microscopy (hence "minimal change")
• The only abnormality is podocyte foot process effacement visible on electron microscopy

Minimal Change Disease: Glomerulus showing normal basement membranes and absence of proliferation (PAS stain). - Robbins & Kumar Basic Pathology

Pathogenesis

1. Podocyte injury → slit diaphragm disruption
2. Selective proteinuria (mainly albumin - smaller plasma proteins)
3. Hypoalbuminemia → reduced plasma oncotic pressure
4. Fluid shifts to interstitium → edema (starts periorbitally/face, then ascites, scrotal/labial edema, pleural effusion)
5. Compensatory RAAS activation → sodium and water retention (worsening edema)
6. Hepatic lipoprotein overproduction → hyperlipidemia

Workup to Confirm

Note: In a child aged 1-12 years with typical nephrotic syndrome and no atypical features (hypertension, hematuria, renal impairment, hypocomplementemia), biopsy is usually deferred and empiric steroid therapy is started - as >90% will have MCD and respond.

Treatment

1. First-Line: Oral Corticosteroids (Prednisolone)

• Prednisolone: 60 mg/m²/day (or 2 mg/kg/day, max 60 mg) as a single morning dose for 4-6 weeks
• Then 40 mg/m² on alternate days for 4-6 weeks, then taper
• >90% of children with MCD achieve complete remission (proteinuria clears) within 2-4 weeks

2. Supportive Measures

3. Relapsing Disease

• Relapses occur in >2/3 of initial responders
• Frequently relapsing / Steroid-dependent: Add steroid-sparing agents:
  • Levamisole (low-cost, well tolerated)
  • Oral cyclophosphamide (for remission consolidation)
  • Mycophenolate mofetil (MMF)
  • Calcineurin inhibitors (tacrolimus, cyclosporine)
  • Rituximab (for difficult steroid-dependent cases)

4. Biopsy Indications in This Age Group

• Age <1 year or onset in infancy (congenital NS)
• Persistent hematuria / low complement
• Hypertension at presentation
• Renal impairment at presentation
• No response to steroids after 8 weeks (steroid-resistant NS)

Prognosis

• Excellent in MCD - does not cause kidney failure
• Most children enter remission with steroids and outgrow the disease by adolescence
• Significant steroid side effects (growth impairment, weight gain, hypertension, cataracts) are the main long-term concern with relapsing courses

Other Causes to Consider (if Atypical)

DKA management in casualty / emergency department

1. Immediate assessment: ABCDE

• Airway and breathing: Give oxygen only if hypoxemic or in shock. Look for Kussmaul breathing.
• Circulation: HR, BP, perfusion, capillary refill, pulses, urine output, body weight.
• Disability: GCS/mental status, headache, vomiting, abnormal behavior, seizures. These may signal cerebral edema.
• Establish 2 IV lines if possible. Cardiac monitor and strict input-output chart.
• Keep NPO initially if vomiting, drowsy, or severely unwell.

2. Confirm DKA and send initial investigations

• Glucose >200 mg/dL (>11 mmol/L)
• Blood beta-hydroxybutyrate ≥3 mmol/L, or urine ketones moderate/large
• Venous pH <7.30 or serum bicarbonate <18 mmol/L

• Bedside glucose and blood ketones
• VBG: pH, bicarbonate, pCO₂
• Electrolytes, urea, creatinine, calcium, magnesium, phosphate
• CBC, infection evaluation if clinically indicated
• ECG, especially if potassium abnormal
• Urinalysis and culture if infection suspected
• Calculate corrected sodium and anion gap

3. Fluids: start before insulin

If shock or poor perfusion

• 0.9% saline 20 mL/kg IV rapidly, reassess after each bolus.
• Repeat only if necessary, with senior/PICU input.

If not in shock

• 0.9% saline 10-20 mL/kg over 20-30 minutes.
• Then replace the remaining maintenance plus estimated deficit gradually, usually over about 36-48 hours, according to the pediatric DKA protocol.
• Use isotonic fluid initially. Avoid excessive fluids.

4. Potassium: check before starting insulin

• Ensure urine output and renal function are assessed before substantial potassium replacement.
• Check potassium at baseline, around 2 hours after insulin begins, then at least every 4 hours. The adult consensus target is K+ 4-5 mmol/L, and pediatric protocols use frequent reassessment due to high risk of rapid decline. The 2024 consensus summary emphasizes delaying insulin if potassium is low.

5. Insulin infusion: begin only after initial fluids

• Regular insulin IV infusion 0.05-0.1 units/kg/hour
• In many children, start 0.05 units/kg/hour for mild/moderate DKA and consider 0.1 units/kg/hour for severe DKA, following local pediatric protocol.
• Do not give an IV insulin bolus in children.

6. Add dextrose but continue insulin

• Add 5% dextrose to IV fluid.
• If glucose continues to fall but ketosis persists, increase to 10% dextrose as per protocol.
• Continue insulin infusion until ketoacidosis resolves.

7. Monitoring

8. Cerebral edema: recognize and treat immediately

• Headache, irritability, confusion, drowsiness
• Recurrent vomiting
• Bradycardia, rising BP
• Cranial nerve palsy, unequal pupils
• Seizure or reduced GCS

1. Call PICU/anesthesia immediately.
2. Elevate head of bed to 30 degrees, keep neck neutral.
3. Reduce IV fluid rate if appropriate, without stopping necessary resuscitation.
4. Give either:
   • Mannitol 0.5-1 g/kg IV over 10-15 min, or
   • 3% hypertonic saline 2.5-5 mL/kg IV over 10-15 min
5. Prepare for airway protection if consciousness is deteriorating.

9. Bicarbonate and phosphate

• Bicarbonate is not routinely indicated. Consider only in extreme acidosis, usually pH <6.9, with hemodynamic compromise or life-threatening hyperkalemia, after senior/PICU consultation.
• Do not routinely give phosphate. Replace if severe hypophosphatemia or if there is muscle weakness, respiratory failure, or cardiac dysfunction.

10. Resolution and transition to subcutaneous insulin

• Child is clinically improved and can eat/drink
• Venous pH ≥7.30 or bicarbonate ≥18 mmol/L
• Blood beta-hydroxybutyrate is low, ideally <0.6 mmol/L

• Give the first SC basal-bolus insulin dose.
• Overlap IV insulin for 30-60 minutes after rapid-acting SC insulin, or longer as required after basal insulin, according to the insulin regimen.
• Treat the precipitating cause and arrange diabetes education before discharge.

Quick casualty order

1. ABCDE, monitors, two IV lines, weigh patient.
2. Bedside glucose and ketones, VBG, electrolytes, ECG.
3. 0.9% saline 10-20 mL/kg over 20-30 min. Give 20 mL/kg rapidly only if shock.
4. Check potassium and add KCl as appropriate.
5. Start IV regular insulin 0.05-0.1 U/kg/h after 1 hour of fluids, with no bolus.
6. Add dextrose at glucose 250-300 mg/dL, continue insulin until ketones/acidosis resolve.
7. Hourly glucose and neuro checks. Watch actively for cerebral edema.