membranous glomerulonephritis; mesangiocapillary glomerulonephritis (membranous nephropathy)

Etiology

• autoimmune (primary)
  • 75-85% with PLA2R antibody
• secondary to systemic disease
  • connective tissue disease
    • systemic lupus erythematosus
    • Sjogren's syndrome
  • sarcoidosis
  • malignancy (1.5% of cases)
    • lung cancer
    • breast cancer
    • gastric cancer
    • pancreatic cancer
    • colon cancer
    • bladder cancer
    • sarcomas
      • lymphomas, leukemias
    • carcinoid
    • malignancies occur at 5 times the expected rate in patients with membranous glomerulonephritis
  • infections
    • hepatitis B, hepatitis C
    • quartan malaria
    • syphilis
    • HIV1 infection
  • sickle cell disease
  • pharmacologic agents
    • gold
    • D-penicillamine
    • captopril
    • probenecid
    • some NSAIDs
    • TNF-alpha inhibitors
    • tiopronin
  • heavy metals - mercury, gold
  • thyroid disease

Epidemiology

• primary cause of idiopathic nephrotic syndrome in white adults (50%) & in patients > 70 years of age
  • 18-41% of total nephrotic syndrome
• mean age of onset is 35 years

Pathology

• deposition of cationic antigens in subepithelial space
• 'spike & dome' epithelial deposits of basement membrane material
• thickening of glomerular capillary wall
• immunofluorescence shows subepithelial granular deposits of IgG4 & C3 (PLA2R antibody)
• electron miscroscopy shows podocyte foot process effacement consistent with protein leakage through the glomeruli

Genetics

• implicated genes: LRPAP1 (p39RAP)

Clinical manifestations

• typically presents with nephrotic syndrome with preserved GFR
  • see nephrotic syndrome
• onset may be abrupt
• slow progression with spontaneous remissions & exacerbations
• hypertension (40%)
• end-stage renal disease (20%)

Laboratory

• 24 hour urine: protein generally > 3.5 g (75%)
• creatinine clearance & glomerular filtration rates are generally near normal
• urinalysis
  • microscopy: urine sediment generally unremarkable
  • microscopic hematuria common
  • erythrocyte casts absent
• serum complement levels are normal
• hepatitis serology
• antinuclear antibody
• PLA2R antibody in serum (phospholipase A2 receptor antibody)
  • ~100% specific for primary membranous glomerulonephropathy
  • obviates need for renal biopsy if no evidence of other pathology
• lipid panel
• renal biopsy needed for diagnosis

* also see ARUP consult

Diagnostic procedures

• renal ultrasound with doppler (rule out renal vein thrombosis)
  • CT angiography is preferred procedure
• renal biopsy confirms diagnosis
• colonoscopy (rule out colon cancer)

Radiology

• CT angiography to rule out renal vein thrombosis
• mammography (rule out breast cancer)
• chest X-ray or low-dose non-contrast chest CT (rule out lung cancer)

Complications

• renal vein thrombosis (25-50%)
  • may cause acute renal failure
  • membranous nephropathy is most likely cause of nephrotic syndrome to result in renal vein thrombosis
• systemic venous thromboembolism
  • pulmonary embolism, deep vein thrombosis
• progression to end-stage renal disease
  • risk factors
    • male > 50 years of age
    • low GFR
    • hypertension
    • secondary glomerulosclerosis & chronic tubulointerstitial nephritis on renal biopsy
  • nephrotic syndrome

Management

• not all patients require treatment; without therapy
  • 25-30% of patients will have complete remission within 1 year
  • 50% of patients will have partial remission
  • 20% of patients will progress to end-stage renal disease
  • observe for 6-12 months to allow time for spontaneous remission prior to initiating immunosuppressive therapy
• nephrotic syndrome
  • supportive therapy, unless complications such as acute renal failure, anasarca, deep vein thrombosis
  • loop diuretic for edema. add metolazone as needed
• immunosuppressive therapy should be reserved for patients with high risk of progression to end-stage renal disease, nephrotic syndrome
  • high dose alternate day glucocorticoids
  • combination of cytotoxic agent & glucocorticoids
    • cyclosporine (Sandimmune)
    • mycophenolate (Cellcept)
    • tacrolimus
    • other cytotoxic agents
      • cyclophosphamide (Cytoxan)
      • azathiaprine (Imuran)
      • chlorambucil (Leukeran)
  • rituximab may be a 1st-line treatment option in selected patients
  • calcineurin inhibitors
• ACE inhibitors may diminish the degree of proteinuria
• control hypertension
• treat underlying disorder
  • lamivudine may benefit nephropathy in patients with hepatitis B
• optimal therapy not established
• screening for cancer (see etiology) determined by additional risk factors (if any)
  • extensive screening not indicated

More general terms

• glomerulonephritis (GN, nephritic syndrome)

Additional terms

• nephrotic syndrome
• renal vein thrombosis
• systemic lupus erythematosus