Minimal Change Disease

Minimal change disease (MCD) is a podocytopathy causing nephrotic syndrome, with normal glomeruli on light microscopy and diffuse foot process effacement on electron microscopy.

• Causes 70 to 90% of nephrotic syndrome in children under 10 years and 10 to 15% in adults.
• Pathogenesis: T cell and B cell dysfunction with circulating permeability factors (anti-nephrin antibodies, cytokines).
• Secondary causes in adults: NSAIDs, lithium, Hodgkin lymphoma and other malignancy, infections, allergy, atopy.
• Steroid sensitivity is high (over 90% in children, 80% in adults), but relapses are frequent (about 70% in children, 50% in adults).
• Complications: oedema, infection (peritonitis, cellulitis), thrombosis, hypovolaemia with AKI (adults), steroid toxicity.

• Rapid onset of periorbital then generalised oedema, ascites, pleural effusions, foamy urine, weight gain.
• Hypertension is uncommon in children; adults may have AKI and hypertension.
• Preceding infection or allergy in some.
• Complications: abdominal pain (peritonitis), thromboembolism, hypovolaemic shock.

• Proteinuria over 3.5 g/24 hours (urine protein to creatinine ratio over 2 g/g, or over 200 mg/mmol in children), albumin under 25 g/L, hyperlipidaemia, bland sediment, normal complement.
• Children with typical features (age 1 to 10, no haematuria, hypertension or renal impairment) are treated empirically without biopsy.
• Adults require renal biopsy: normal light microscopy, negative immunofluorescence (or minimal IgM), foot process effacement.
• Screen for secondary causes: hepatitis B and C, HIV, ANA, malignancy screen in older adults, drug history.
• Baseline: lipids, creatinine, HbA1c, TB screen and hepatitis B status before immunosuppression.

Supportive

• Sodium restriction (under 2 g/day), loop diuretics (furosemide 20 to 80 mg), albumin infusion only for severe hypovolaemia, ACE inhibitor if hypertensive, vaccination (pneumococcal), statin if persistent.
• Thromboprophylaxis with LMWH for albumin under 20 g/L with additional risk.

Immunosuppression

• Adults: prednisolone 1 mg/kg (maximum 80 mg) daily for 4 to 16 weeks until remission (about 2 to 3 weeks after proteinuria resolves), then taper over 6 months.
• Children: prednisolone 60 mg/m2 (maximum 60 mg) daily for 4 to 6 weeks, then 40 mg/m2 on alternate days for 4 to 6 weeks.
• Frequent relapse or steroid dependence: cyclophosphamide 2 mg/kg for 8 to 12 weeks, tacrolimus 0.05 to 0.1 mg/kg/day (trough 5 to 8 ng/mL), ciclosporin 3 to 5 mg/kg/day, mycophenolate mofetil 1 g twice daily, or rituximab 375 mg/m2 weekly for 4 doses (or 1 g twice) which induces sustained remission in many.
• Steroid resistance (rare): repeat biopsy to exclude FSGS, genetic testing in children, calcineurin inhibitor.
• Infection prophylaxis, bone protection, growth monitoring.
• Follow up with urine dipstick or protein at each relapse, and renal function annually.