Renal/Urology · PANCE / PANRE

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

FeatureMinimal change diseaseFSGS
Most common ageChildren 2-6Adults, especially Black patients
HematuriaRareCommon
HypertensionUncommonCommon
Light microscopyNormalFocal segmental sclerosis
EM foot-process effacementDiffuseDiffuse (primary) or segmental (secondary)
Steroid response~90% in children~30-50% in adults
Progression to ESKDRareCommon in untreated primary
MCD vs FSGS — overlapping presentations distinguished by biopsy and steroid response.

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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