New Concept of MPGN

The diagnosis of membranoproliferative glomerulonephritis (MPGN) or mesangiocapillary GN is based on renal biopsy. The light microscope (LM) shows lobular pattern of glomeruli with endocapillary proliferation and double contour of their capillary walls. Immunofluorescence (IF) typically shows positivity with IgG and C3 except for type II or dense deposit disease in which only C3 is positive.

Traditionally MPGN is classify into 3 type: I, II, and III. Electron microscope (EM) differentiates these 3 types by the different location of electron dense deposits.

Recently an entity called C3 glomerulonephritis has been recognized. It has LM and EM features similar to MPGN I or II, but IF show only C3 staining.

A review article on NEJM last month proposed a new way to look at MPGN. LM identifies MPGN and then IF defines whether it is immunoglobulin (Ig) positve and C3 positive or Ig negative and C3 positive. When the former is identified, the underlying conditions must by sought out. These include autoimmune diseases, infections (especially hepatitis C) and monoclonal gammopathy. The latter is the result of dysregulation in alternative complement pathway. The cause could be genetics in which mutations regulating protein such as factor H or I occur, or the presence of antibodies to these proteins.

With this new perspective, MPGN I, II could be either Ig+/C3+ or Ig-/C3+, while MPGN II and C3 GN are Ig-/C3+. This change of concept reflects our increased understanding of etiology and pathogenesis of this glomerular disease. The original, morphological-based classification starts to give way to the new, pathogenesis-base approach.