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Membranous Nephropathy

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Overview

Also known as membranous glomerulonephritis and not to be confused with membranoproliferative glomerulonephritis, membranous nephropathy (MN) is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) being the first.

The pathophysiology of MN is thought to be due to the formation of immune complexes as a result of antibodies binding to antigens in the glomerular basement membrane (GBM).

Epidemiology

  • MN is the second most common cause of nephrotic syndrome in adults
  • MN is the third most common cause of end-stage renal failure (ESRF)
  • The mean age of diagnosis is 50-60 years, but MN can affect people of all ages
  • MN is more common in men

Risk Factors

  • Autoimmune disease (e.g. systemic lupus erythematosus, rheumatoid arthritis)
  • Hepatitis B and C – immune complexes can deposit in the glomeruli
  • Syphilis
  • Malignancy – particularly lung and colorectal due to tumour antigens deposited in the glomeruli and immune complex formation
  • Some medications – NSAIDs, lithium, and penicillamine

Presentation

Patients present with nephrotic syndrome:

  • Proteinuria (>3.5 g/24hr)
  • Hypoalbuminaemia
  • Oedema

Other features that may also be seen in nephrotic syndrome include:

  • Hyperlipidaemia
  • Hypercoagulability
  • Immunodeficiency

Additional features include:

Hypertension – may be due to volume overload or renal dysfunction

Fatigue and malaise – may suggest an underlying cause (e.g. an autoimmune disease)

Differential Diagnoses

Focal segmental glomerulosclerosis (FSGS)

  • Both present similarly
  • In FSGS, light microscopy shows focal segmental areas of mesangial sclerosis and immunofluorescence microscopy is unremarkable

Minimal change disease (MCD)

  • More common in children
  • Both present similarly, although hypertension is less common in MCD
  • Light microscopy and immunofluorescence are normal in MCD
  • Electron microscopy shows diffuse podocyte effacement

Investigations

  • Urinalysis:
    • Proteinuria is seen
    • No significant haematuria is generally seen
  • Urine microscopy and culture:
  • 24-hour urinary protein or urine protein:creatinine ratio:
    • Shows proteinuria
  • Urea and electrolytes (U&Es) and estimated glomerular filtration rate (eGFR):
    • Urea and creatinine may be elevated
  • Estimated glomerular filtration rate (eGFR):
    • May be reduced
  • Serum albumin:
    • May be low
  • Serum lipids:
    • Shows hypertriglyceridaemia/hypercholesterolaemia
  • C3 and C4 complement levels:
    • May be low if SLE present
  • Liver function tests (LFTs):
    • To rule out chronic liver disease as a cause of hypoalbuminaemia
  • Renal ultrasound:
    • To rule out structural abnormalities
  • Kidney biopsy – gives definitive diagnosis:
    • Light microscopy shows diffuse thickening of the GBM
    • Immunofluorescence shows diffuse granular IgG and C3 deposits along the GBM
    • Electron microscopy

Management

  • Manage underlying cause (if applicable)
  • ACE inhibitor or angiotensin-II receptor blocker (ARB):
    • Reduces proteinuria, slows progression, and controls hypertension
  • Statins:
    • If hyperlipidaemia is present
  • Immunosuppression with corticosteroids and another agent such as cyclophosphamide

Complications

The main complication is chronic kidney disease and its associated complications (e.g. hypertension and cardiovascular disease, CVD). CVD can also occur due to hyperlipidaemia due to nephrotic syndrome.

Other complications include:

  • Hypercoagulability – due to loss of antithrombin III in nephrotic syndrome
  • Increased risk of infection – due to loss of immunoglobulins in nephrotic syndrome

Prognosis

  • Around 1/3 of patients undergo spontaneous remission
  • The prognosis is worse if the patient is male, is older at diagnosis, and with greater levels of proteinuria

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