minimal change disease; minimal change glomerulonephropathy (MCD)

Etiology

• generally idiopathic
• secondary causes
  • atopy
    • pollen, dairy products
  • infections:
    • strongyloides
    • syphilis
    • mycoplasma
    • ehrlichiosis
    • infectious mononucleosis
  • malignancies
    • Hodgkin's disease
    • non-Hodgkin's lymphoma
    • leukemias
    • thymoma
    • gastrointestinal cancers
    • kidney cancers
  • pharmaceuticals
    • NSAIDs (with interstitial nephritis)
    • lithium carbonate
    • rifampin
    • interferons
    • pamidronate

Epidemiology

• most common cause of nephrotic syndrome in children
• accounts for 10-20% of adult cases of nephrotic syndrome
  • 9-16% of total nephrotic syndrome

Pathology

• T-cell lymphokine attack on glomerular epithelial cells
• fusion of epithelial cell foot processes (EM)
• loss of heparin sulfate basement membrane negative charge
• light microscopy & immunofluorescence are normal

Clinical manifestations

• patients present with abrupt-onset of nephrotic syndrome
• hypertension may be present
• a single episode of nephrotic syndrome followed by a long remission in 30%
• relapsing course in 60%
  • relapses usually occur within the 1st 6 months of remission
• progression to chronic renal failure is uncommon

Laboratory

• serum creatinine
  • generally normal in children
  • up to 15% of adults with acute renal failure
    • risk factors: hypertension, hypoalbuminemia, heavy proteinuria, hypovolemia & NSAID-associated interstitial nephritis
• urinalysis
  • microscopic hematuria
  • selective proteinuria
• serum complement levels are normal
• serum IgG decreased, IgM increased
• renal biopsy
  • generally not done in the absence of hematuria, pyuria, erythrocyte casts & leukocyte casts
  • generally normal on light microcsopy
  • no immune-complexes on immunofluorescence
  • foot process fusion by electron microscopy

Differential diagnosis

• early focal segmental glomerulosclerosis
• membranous glomerulonephritis
  • onset of edema generally slower
  • acute renal failure generally due to renal vein thrombosis

Management

• glucocorticoids are initial treatment of choice
  • prednisone dosing:
    • start 1 mg/kg/day; taper over 3 months, then discontinue
    • 60 mg QD or QOD for 4 weeks, followed by 40 mg/m2 for 4 weeks
  • 80% of patients respond by decreased proteinuria
  • monitor urinary protein during steroid taper
  • reinstitute glucocorticoid for relapse after initial remission
• treatment failure
  • failure to respond to 16 weeks of therapy (adults)
  • often associated with misdiagnosis
• immunosuppressive agents for relpase or treatment failure
  • cyclophosphamide (Cytoxan) - 2 mg/kg/day PO for 8 weeks
  • calcineurin inhibitors: cyclosporine
  • mycophenolate
  • rituximab
  • chlorambucil (Leukeran)
    • 0.2 mg/kg/day PO for 8-12 weeks
  • levamisole
• prognosis: < 5% of patients progress to end-stage renal disease

More general terms

• glomerulonephropathy; glomerulopathy

Additional terms

• focal segmental glomerulosclerosis (FSGS)
• nephrotic syndrome