Membranoproliferative Glomerulonephritis

Membranoproliferative Glomerulonephritis

 

Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular injury defined by mesangial expansion, cellular proliferation and double contouring of glomerular basement membrane. It was historically classified according to the relationship of electron dense deposits to the glomerular basement membrane (type 1 – sub-endothelial, 2 – intramembranous and 3 – sub-endothelial and sub-epithelial).

 

An MPGN pattern of glomerular injury (usually type 1 or type 3) is associated with a number of secondary causes. These usually have a pattern of C3 and immunoglobulin staining on IF and are best classified as immune-complex MPGN. MPGN has also been historically associated with C3 dominant staining on IF, (a pattern now better recognised as C3G). Secondary causes of MPGN (usually immune-complex MPGN) include infective diseases, auto-immune conditions and haematological disorders. A list of possible causes that could be considered are listed below. Drusen, age-related macular degeneration and acquired partial lipodystrophy have been reported in association with MPGN. Familial history has been reported in cases of MPGN.

 

A pattern of C3 dominant staining on IF was previously recognised in all types of MPGN that prompted the possibility of a disorder of complement regulation. These have now been reclassified as C3G (with MPGN).

 

Secondary causes of MPGN

Autoimmune diseases

  • Systemic lupus
  • Sjogren’s syndrome
  • Rheumatoid arthritis
  • Mixed connective tissue disease

Infections

  • Hepatitis B
  • Hepatitis C
  • Epstein-Barr virus
  • Human immunodeficiency virus
  • Endocarditis
  • Shunt infections
  • Visceral abscesses
  • Leprosy
  • Malaria
  • Schistosomiasis
  • Mycoplasma
  • Brucellosis

Neoplasms/Paraproteinaemias

  • Monoclonal gammopathy of undetermined significance
  • Plasma Cell dyscrasia
  • Waldenstrom macroglobulinaemia
  • Chronic lymphocytic leukaemia
  • Low-grade B-cell lymphoma
  • Cryoglobulinaemia type 1 and 2
  • Immunotactoid glomerulopathy
  • Monoclonal Ig deposition disease
  • Fibrillary glomerulopathy
  • Carcinomas, Wilms’ tumour, malignant melanoma

Chronic liver disease

  • Chronic active hepatitis (B,C)
  • Cirrhosis
  • Alpha-1 antitrypsin deficiency

Miscellaneous 

  • Thrombotic microangiopathy
  • Sickle cell disease
  • Transplant glomerulopathy
  • Niemann-Pick disease (Type C)