Key Facts

MCD is a podocytopathy where T-cell-derived circulating factors damage podocytes, causing proteinuria. It is defined by the absence of significant changes on light microscopy with characteristic foot process effacement on EM.

Epidemiology

• Commonest cause of nephrotic syndrome in children (80%) – peak age 2-6 years
• 10-15% of adult nephrotic syndrome
• Annual incidence in children: 2-4 per 100,000
• M:F ratio in children: 2:1; adults: equal

Aetiology

• Primary/idiopathic: majority of cases
• Secondary causes: NSAIDs, lithium, interferon, lymphoma (Hodgkin), atopy, infections
• T-cell dysfunction with production of circulating permeability factors is hypothesised

Pathophysiology

• Circulating factors (likely T-cell derived) damage podocytes and disrupt the glomerular filtration barrier
• Loss of podocyte foot processes (effacement) → loss of charge-selective barrier → selective proteinuria (mainly albumin)
• No immune complex deposition, no complement activation
• Normal GBM on EM
• Associated with atopy and lymphoma suggests immune dysregulation

Classic Presentation

• Sudden-onset generalised oedema: periorbital (especially morning), peripheral, scrotal/labial, ascites
• Frothy urine (heavy proteinuria)
• Often preceded by URTI or atopic flare

Nephrotic Syndrome Features

• Proteinuria >3.5g/day (often >10g/day)
• Hypoalbuminaemia (<25 g/L)
• Hyperlipidaemia (raised cholesterol and triglycerides)
• Lipiduria: oval fat bodies, maltese cross under polarised light

Complications

• Infection: peritonitis (particularly pneumococcal), cellulitis – due to immunoglobulin loss
• Thromboembolism: DVT, PE, renal vein thrombosis – due to loss of antithrombin III
• Acute kidney injury: hypovolaemia, sepsis

Red Flags

• AKI at presentation → consider MCD with ATN or consider alternative diagnosis
• Adult-onset MCD → screen for secondary causes (lymphoma, drugs)
• Steroid resistance → reconsider diagnosis (may be FSGS on repeat/deeper biopsy)

Bedside

• Urinalysis: heavy proteinuria (3-4+ on dipstick), no haematuria
• Blood pressure: usually normal or low in children
• Weight: daily (fluid status monitoring)

Bloods

• Serum albumin: low (<25 g/L, often <15 g/L)
• Urine PCR: very high (often >300 mg/mmol)
• U&Es: usually normal renal function (AKI in 5%)
• Lipid profile: raised cholesterol and triglycerides
• FBC: haemoconcentration
• Immunoglobulins: low (particularly IgG)
• Complement (C3/C4): normal

Imaging

• Renal ultrasound: normal-sized kidneys; exclude other pathology
• Chest X-ray: pleural effusions in severe nephrotic syndrome

Special Tests

• Renal biopsy: NOT required in typical childhood MCD (children <12 with classic features treated empirically with steroids)
• Biopsy indicated: adults with nephrotic syndrome, steroid-resistant children, atypical features
  • LM: normal
  • IF: negative
  • EM: diffuse podocyte foot process effacement (diagnostic)
• Selectivity index: highly selective proteinuria (mainly albumin); less used now

Non-pharmacological

• Fluid and sodium restriction during oedema
• Dietary advice: adequate protein intake, avoid excessive salt
• Pneumococcal vaccination: if not previously immunised
• Thromboprophylaxis: consider if albumin <20 g/L and additional risk factors

Pharmacological

Children (first episode):

• Prednisolone 60mg/m²/day (max 80mg) for 4 weeks, then 40mg/m² on alternate days for 4 weeks, then taper over 2-4 weeks
• PREDNOS trial: longer initial course (16 weeks) reduces relapse rate vs 8 weeks

Adults:

• Prednisolone 1mg/kg/day (max 80mg) for a minimum of 4 weeks (up to 16 weeks if needed)
• Slower response than children: 70-80% achieve remission
• Taper over 6 months

Relapsing/steroid-dependent:

• Cyclophosphamide 2mg/kg/day for 8-12 weeks (induces prolonged remission in 70-80%)
• Ciclosporin 3-5mg/kg/day or tacrolimus 0.05-0.1mg/kg/day: steroid-sparing; high relapse on discontinuation
• Mycophenolate mofetil 500mg-1g BD: alternative steroid-sparing agent
• Rituximab 375mg/m² × 1-2 doses: increasingly used for frequently relapsing/steroid-dependent MCD; sustained remission in 60-80%

Symptomatic:

• Diuretics (furosemide + spironolactone) for oedema
• IV albumin 20% (100mL) + furosemide: for severe hypovolaemic oedema
• Statins: for persistent hyperlipidaemia
• Prophylactic penicillin V: during active nephrotic syndrome in children

Referral Criteria

• All adults with nephrotic syndrome → nephrology
• Steroid-resistant children → paediatric nephrology
• Frequently relapsing (≥2 relapses in 6 months or ≥4 in 12 months)

• Children: 90-95% achieve complete remission with steroids; 50-70% relapse
• Adults: 70-80% respond to steroids (but slower, over weeks-months)
• Steroid-resistant cases (~5% children, ~20% adults): re-biopsy to exclude FSGS
• Progression to ESRD: very rare (<5% overall)
• Remission off all treatment: achieved by >80% by adulthood
• Mortality from complications (infection, thromboembolism) is rare with modern management
• Cyclophosphamide induces sustained remission in 70-80% of frequently relapsing cases

Nephrotic Syndrome – Key Complications

PREDNOS Trial

• Compared 8-week vs 16-week prednisolone course in childhood nephrotic syndrome
• Extended course significantly reduced relapse rate at 2 years

Steroid-Sparing Agent Comparison