membranoproliferative glomerulonephritis

Classification

• type 1: antigen-antibody reactions trigger classic complement pathway
• type 2: hyperactive alternative complement pathway

Etiology

• idiopathic
  • type 1
  • type 2 (dense deposit disease)
• secondary
  • chronic infection
  • "shunt nephritis"
  • malaria
  • hepatitis C >> hepatitis B or HIV1*
  • systemic lupus erythematosus (SLE)
  • Sjogren's syndrome
  • congenital complement deficiency (C2,C3)
  • mixed cryoglobulinemia
  • sickle cell disease
  • partial lipodystrophy (type 2)
  • alpha-1 antitrypsin deficiency
  • subacute endocarditis
  • malignancies
    • monoclonal gammopathy (multiple myeloma)

* hepatitis B & HIV1 associated with nephrotic syndrome

* hepatitis B associated with membranous glomerulopathy

* HIV1 associated with focal segmental glomerulosclerosis

Epidemiology

• rare form of chronic glomerulonephritis
• children & young adults

Pathology

• duplication, splitting, tramtracking or double contouring of glomerular basement membrane (light microscopy)
• lobular appearance of glomeruli from
  • glomerular basement membrane proliferation
  • capillary loop thickening
• immunofluorescence shows immune complex deposition in the mesangium & capillary walls
  • type 1: diffuse C3, variable IgG, IgM
  • type 2: C3 in capillary wall & mesangial nodules
• electron microscopy shows ribboning or sausaging of dense material in type II membranoproliferative glomerulonephritis

Genetics

• implicated genes: LOI

Clinical manifestations

• commonly presents as chronic glomerulonephritis
  • may present as acute glomerulonephritis
• may present as nephrotic syndrome (50%)
• may present as asymptomatic hematuria & proteinuria (30%)
• may present as acute renal insufficiency
• generally, slow progression to renal failure

Laboratory

• urinalysis
  • microscopic hematuria
    • dysmorphic RBC & RBC casts suggestive of glomerular disease
  • 24 hour urine: proteinuria (< 3.5 g/day)
• serum complement C3, C4 are persistently low (> 8 weeks) in type 2, & may be intermittently low in type 1
• antistreptolysin-O (ASO) may be positive
• C3-nephritic factor is frequently present
• renal biopsy
  • mesangial proliferation
  • subendothelial glomerular basement membrane deposits (type 1)
  • intramembranous glomerular basement membrane deposits (type 2)

Management

• supportive care
• treatment of underlying disorder
• glucocorticoids have been helpful in some children
• dipyridamole 225 mg QD & aspirin 975 mg/day has been used to slow progression of disease in adults
• immunosuppressive therapy when nephrotic syndrome or renal failure
  • cyclosporine + prednisone has been used
• eculizumab may be useful for complement-mediated forms
• no therapy has been shown to improve disease-free survival
• > 50% of patients progress to end-stage renal disease within 15 years
• poor prognostic indicators
  • hypertension
  • renal insufficiency
  • heavy proteinuria
• disease tends to recur with renal transplantation
  • type 1 30%
  • type 2 90%

More general terms

• glomerulonephritis (GN, nephritic syndrome)

Additional terms

• alpha-1 antitrypsin deficiency
• complement C3 nephritic factor
• hepatitis B virus (HBV)
• lipodystrophy; lipoatrophy
• malaria
• nephrotic syndrome
• sickle cell (hemoglobin SS) disease
• systemic lupus erythematosus
• type 2 (mixed) cryoglobulinemia