Membranoproliferative glomerulonephritis

Abstract

Membranoproliferative glomerulonephritis is an uncommon kidney disorder characterized by mesangial cell proliferation and structural changes in glomerular capillary walls. It can be subdivided into idiopathic and secondary forms, which are differentially diagnosed by a review of clinical features, laboratory data, and renal histopathology. Three types-I, II, and III-have been defined by pathologic features. All three types are associated with hypocomplementemia, but they manifest somewhat different mechanisms of complement activation. Type II, also known as "dense deposit disease", is associated with the presence of C3-nephritic factor. Membranoproliferative glomerulonephritis primarily affects children and young adults, with patients presenting with nephrotic or nephritic syndrome or with asymptomatic renal disease. This type of glomerulonephritis often progresses slowly to end-stage renal disease, and it tends to recur after renal transplantation, especially type II. The efficacy of various forms of treatment remains controversial; however, long-term steroid treatment seems to be effective in children with nephrotic-range proteinuria. Improvement in renal outcomes largely relies on the evaluation of more selective agents in carefully controlled studies.

Fig. 1

Schematic depiction of the complement system highlighting the different pathways of complement activation in the three types of membranoproliferative glomerulonephritis (MPGN). NeFt Nephritic factor of the terminal pathway, P properdin

Fig. 2

In the normal glomerulus (a), the capillary loops are open, the mesangial areas have no more than three nuclei each, and the foot processes are intact, without any deposits or proliferation. In type I MPGN (b), the glomerulus appears to be lobulated due to extensive endocapillary proliferation, and the glomerular basement membrane has a split appearance as a result of the mesangial interposition and subendothelial deposits. In type 2 MPGN (c), the capillary walls appear to be thickened by dense deposits in a ribbon-like pattern, and the mesangial area also contains dense material

Fig. 3

Electron micrographs show subendothelial deposits with intermesangial interposition in type I MPGN (a) and intramembranous dense deposits in type II MPGN (b). Original magnification: a ×25,000, b ×7000

Fig. 4

Treatment options of idiopathic MPGN depending on the level of proteinuria and renal dysfunction. ARB Angiotensin receptor blocking agent, ACEI angiotensin-converting enzyme inhibitor, MMF mycophenolate mofetil

Fig. 5

Management of hepatitis C-associated cryoglobulinemic MPGN. GFR Glomerular filtration rate, * as described in the opposite box under proteinuria <3g/d