Minimal Change Disease
Steroid-responsive nephrotic syndrome with normal light microscopy and diffuse foot-process effacement.
Also known as: MCD, minimal change disease, nil disease, lipoid nephrosis
Overview
A podocytopathy characterized by nephrotic syndrome with normal-appearing glomeruli on light microscopy, absent immune deposits on immunofluorescence, and diffuse podocyte foot-process effacement on electron microscopy. The most common cause of nephrotic syndrome in children.
Epidemiology
Causes ~90% of nephrotic syndrome in children under age 10 and ~10-15% in adults. Peak childhood incidence age 2-6, with a male predominance in pediatrics that disappears in adults. Strong association with atopy and recent upper respiratory infections.
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Risk factors
- Atopy (asthma, eczema, allergic rhinitis)
- Recent viral upper respiratory infection
- NSAIDs (often combined with acute interstitial nephritis)
- Hematologic malignancy — particularly Hodgkin lymphoma; less commonly non-Hodgkin lymphoma and leukemia
- Lithium therapy
- Bee or insect sting hypersensitivity
- Immunotherapy: interferon, ipilimumab, pembrolizumab
Pathophysiology
MCD is felt to be a T-cell–mediated podocytopathy. A circulating factor (possibly anti-nephrin antibodies, IL-13, or hemopexin) alters the podocyte cytoskeleton, neutralizes the negatively charged glomerular filtration barrier, and produces selective loss of albumin into the urine. Foot-process effacement is diffuse but reversible, explaining the rapid response to corticosteroids and the absence of structural damage on light microscopy.
Clinical presentation
Symptoms
- Abrupt onset (often within days) of periorbital and dependent edema
- Foamy urine, weight gain, decreased urine output
- Children may present with abdominal pain from ascites or peritonitis
- Symptoms often follow a viral illness or allergen exposure
Signs / physical exam
- Generalized edema (periorbital, scrotal/vulvar, pretibial, ascites)
- Blood pressure usually normal or only mildly elevated (unlike FSGS)
- Generally no hematuria; if microscopic hematuria present, consider alternate diagnoses
Classic findings
Heavy 'selective' proteinuria (predominantly albumin) with rapid corticosteroid response — sometimes within 1-2 weeks in children.
Differential diagnosis
- FSGS — Segmental sclerosis on biopsy, higher rate of hypertension/hematuria, often steroid-resistant
- Membranous nephropathy — Adult-onset nephrotic syndrome; subepithelial deposits, anti-PLA2R antibody
- Diabetic nephropathy — Long-standing diabetes, retinopathy, gradual sub-nephrotic to nephrotic proteinuria
- Amyloidosis — Older adult, monoclonal gammopathy or chronic inflammation; Congo red staining
- Lupus membranous (class V) — Positive ANA/anti-dsDNA, low complements, extrarenal SLE
- IgA nephropathy — Nephritic features (hematuria) usually dominate; mesangial IgA deposits
Diagnostic workup
Diagnostic criteria
In children with classic presentation (age 1-10, no hematuria, no hypertension, normal complement, normal renal function), empiric corticosteroid therapy is initiated without biopsy. Adults and steroid-resistant children require kidney biopsy showing normal LM, negative IF, and diffuse foot-process effacement on EM.
Labs
- Spot urine protein-to-creatinine ratio or 24-hour urine — nephrotic range (>3.5 g/day adult; >40 mg/m²/h child)
- Serum albumin (low, often <2.5 g/dL), lipid panel (elevated)
- BMP — usually normal Cr; AKI can occur from intravascular volume depletion
- C3, C4 — both normal (helps distinguish from membranoproliferative or lupus nephritis)
- Hepatitis B, hepatitis C, HIV, ANA, anti-PLA2R (in adults) to exclude other causes
- Consider age-appropriate malignancy screening in adults (lymphoma history, exam)
Imaging
- Renal ultrasound only if AKI, hematuria, or suspicion of obstruction — usually normal-sized kidneys
Diagnostic algorithm
| Feature | Minimal change disease | FSGS |
|---|---|---|
| Most common age | Children 2-6 | Adults, especially Black patients |
| Hematuria | Rare | Common |
| Hypertension | Uncommon | Common |
| Light microscopy | Normal | Focal segmental sclerosis |
| EM foot-process effacement | Diffuse | Diffuse (primary) or segmental (secondary) |
| Steroid response | ~90% in children | ~30-50% in adults |
| Progression to ESKD | Rare | Common in untreated primary |
Treatment
First-line
- Corticosteroids — prednisone 60 mg/m²/day (max 60 mg) in children for 4-6 weeks, then taper; 1 mg/kg/day (max 80 mg) in adults for up to 16 weeks
- Dietary sodium restriction, fluid management
- Loop diuretic (furosemide, torsemide, bumetanide) for symptomatic edema — use cautiously to avoid intravascular volume depletion
- Albumin infusion before IV diuretic if severe hypoalbuminemia and refractory edema (controversial)
- Pneumococcal vaccination and consideration of penicillin prophylaxis in children with hypogammaglobulinemia
Steroid-sensitive (most pediatric cases)
- Remission within 4 weeks of steroid therapy
- Taper over additional 2-5 months once urine protein negative
Frequent relapsing or steroid-dependent
- Calcineurin inhibitor — cyclosporine, tacrolimus
- Mycophenolate mofetil
- Cyclophosphamide (used historically; gonadotoxicity limits use)
- Levamisole in pediatric protocols (outside the US)
Steroid-resistant
- Reconsider diagnosis — repeat biopsy; FSGS may be the true lesion
- Rituximab
- Calcineurin inhibitor
Second-line / adjunct
- Rituximab — increasing first-line role in frequently relapsing or steroid-dependent MCD
- ACE inhibitor (lisinopril, enalapril) or ARB (losartan, valsartan) for any residual proteinuria
- Statin therapy if persistent dyslipidemia after remission
Complications
- Spontaneous bacterial peritonitis in children with ascites — pneumococcus is the leading pathogen
- Thromboembolism — DVT, PE, renal vein thrombosis (less common than in membranous)
- Acute kidney injury from intravascular volume depletion or interstitial edema
- Steroid toxicity: growth retardation, cataracts, osteoporosis, infection
- Progression to FSGS in steroid-resistant cases on repeat biopsy
PANCE pearls
- Classic pediatric presentation does not require biopsy — empiric prednisone is both diagnostic and therapeutic.
- Hodgkin lymphoma is the classic paraneoplastic association in adults.
- Severe edema with hypoalbuminemia can precipitate intravascular volume depletion and prerenal AKI; diurese cautiously.
- Children with relapse should be screened for SBP if abdominal pain develops.
- Anti-nephrin antibodies have recently been described as a possible serologic marker (2022-2024 literature).
References
- KDIGO 2021 — KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases (Kidney Int 2021;100:S1-S276)
- IPNA — International Pediatric Nephrology Association Clinical Practice Recommendations for Steroid-Sensitive Nephrotic Syndrome (Pediatr Nephrol 2023;38:877-919)
- Anti-nephrin Ab — Watts AJB et al. Discovery of autoantibodies targeting nephrin in minimal change disease (JASN 2022;33:238-252)
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