Minimal Change Disease

Minimal change disease (MCD) gets its name from the fact that the kidney biopsy looks essentially normal under a light microscope. Only on electron microscopy do you see the diagnostic finding: diffuse effacement (flattening) of the podocyte foot processes — the specialised cells that maintain the kidney's filter barrier.

When podocytes lose their normal architecture, large amounts of protein (especially albumin) leak through the filter into the urine.

Who Gets It

• Most common in children aged 2-10 (~70% of childhood nephrotic syndrome)
• Boys > girls in childhood
• Adults: ~15% of adult nephrotic syndrome
• Slightly more common in Asian populations

Causes

• Primary (idiopathic) — most cases; thought to be T-cell driven cytokine release
• Secondary (less common):
• NSAIDs (especially long-term)
• Lithium
• Hodgkin lymphoma (always consider in adults)
• Allergic reactions
• Infections (e.g. mononucleosis)

Typical Presentation

• Sudden onset over days-weeks
• Frothy urine
• Periorbital puffiness (often noticed in mornings)
• Leg and ankle swelling
• Weight gain (fluid)
• Abdominal swelling (ascites)
• Sometimes pleural effusions, breathlessness
• In children: often follows a viral infection

Investigations

• Urine ACR — extremely high (often > 300, may exceed 1,000)
• Serum albumin — low (< 30 g/L = nephrotic; often < 20)
• Cholesterol — very high
• Creatinine — usually normal; can rise from intravascular volume depletion
• Complement, ANA, ANCA, hepatitis B/C, HIV — usually normal/negative
• Anti-PLA2R — negative (rules out membranous)

Kidney Biopsy

• Children with classic presentation: usually not biopsied initially — treat as MCD, biopsy only if no response
• Adults: biopsy is standard before treatment
• Light microscopy: normal
• Immunofluorescence: negative
• Electron microscopy: diffuse podocyte foot process effacement

IMPORTANT — exclude lymphoma in adults presenting with new MCD: examine lymph nodes, do a chest X-ray.

FIRST EPISODE — STEROIDS:

Children

• Prednisolone 60 mg/m² daily (max 60 mg) for 4-6 weeks
• Then alternate-day 40 mg/m² for 4-6 weeks
• Then taper over 2-5 months
• ~90% achieve complete remission within 4 weeks
• Those who remit quickly = good prognosis

Adults

• Prednisolone 1 mg/kg daily (max 60-80 mg) for 8-16 weeks
• Then slow taper over 6+ months
• ~80% complete remission within 16 weeks
• Slower response than children

Supportive

• Salt restriction < 5 g/day
• Fluid restriction if heavy oedema
• Diuretic (furosemide ± spironolactone) for oedema
• ACE inhibitor or ARB if proteinuria persists
• Statin if cholesterol very high (often unnecessary if rapid remission)
• Anticoagulation prophylaxis if albumin < 20 g/L (high VTE risk)
• Pneumococcal vaccination
• Bone protection if prolonged steroids
• PPI gastric protection

RELAPSE (return of proteinuria):

• Treat with prednisolone again, then taper
• Frequent relapses (2 in 6 months) or steroid-dependent → step up to:
• LEVAMISOLE (children)
• CICLOSPORIN or TACROLIMUS (calcineurin inhibitors)
• MYCOPHENOLATE MOFETIL (MMF)
• CYCLOPHOSPHAMIDE (8-week course)
• RITUXIMAB — now increasingly first-choice steroid-sparing agent in adults and frequently-relapsing children

Steroid-resistant

• Reconsider diagnosis — repeat biopsy may show FSGS
• Calcineurin inhibitor often induces remission
• Genetic testing if young or atypical

MOST PATIENTS WITH MCD WILL RELAPSE — this is normal. The aim is to detect relapses early and minimise both proteinuria and steroid exposure.

Home Monitoring

• Daily morning urine dipstick (especially with infections)
• Weight monitoring
• Keep a 'relapse diary'
• Contact your team at first sign of 2+ protein on dip

Infection Risk

• Heavy proteinuria loses immunoglobulins — bacterial infection risk
• Steroids and immunosuppression add to risk
• Pneumovax and meningococcal vaccines before/between immunosuppression
• Live vaccines avoided during immunosuppression
• Annual flu, COVID vaccines
• Penicillin V prophylaxis sometimes used in children

Diet

• Normal protein intake (don't restrict — you're losing protein)
• Low salt during active disease
• Heart-healthy fats (cholesterol is high)
• Adequate calcium and vitamin D (steroids)

Growth In Children

• Long steroid courses can affect growth
• Paediatric nephrology monitors carefully
• Steroid-sparing agents help spare growth

Mental Health

• Nephrotic syndrome and steroids are tough emotionally
• Mood changes, weight gain, body image issues
• Peer support (e.g. Nephrotic Syndrome Trust) helpful

Long-term Outlook

• Most retain normal kidney function for life
• Some have lifelong intermittent relapses but kidneys remain healthy
• Small number (~5%) progress to CKD — usually those reclassified as FSGS
• Adult-onset is slightly more persistent than childhood-onset

Pregnancy

• Best timed during remission off heavy immunosuppression
• Stop teratogenic drugs (MMF, cyclophosphamide) 3 months before conception
• Steroids and ciclosporin acceptable in pregnancy
• Risk of relapse during/after pregnancy — closer monitoring
• Pre-eclampsia risk slightly higher
• Joint renal-obstetric clinic

TRANSPLANT (rare — most don't reach kidney failure):

• If kidney failure does occur, transplant is option
• Recurrence in graft is uncommon (unlike FSGS)
• If recurrence does happen — usually responds to standard treatment

Family Members

• MCD is generally NOT inherited
• Family screening not usually needed
• Exception: genetic forms in some children with steroid-resistant disease — genetic testing may be indicated