Membranoproliferative Glomerulonephritis

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

Membranoproliferative glomerulonephri-tis (MPGN) or mesangiocapillary glo-merulonephritis is a severe type of glo-merulonephritis that is often idiopathic in nature. It affects patients from age 8 to 30. Patients usually present with a nephritic picture (hematuria with red cell casts, non-nephrotic-range proteinuria, hypertension, and renal insufficiency). Characteristic histologic changes seen on light micros-copy include thickening of the GBM, hypercellularity as a result of mesangial cell proliferation and influx of monocytes, and narrowing of the capillary lumens. Immunofluorescence shows extensive complement deposition along the capillary wall. MPGN is classified into three types, depending on the location of dense depos-its seen on electron microscopy. In type I MPGN, immune deposits are found in the mesangium and subendothelial space. This type is a rare finding but appears to be the most benign lesion. Systemic diseases associated with type I MPGN include hep-atitis C infection with and without mixed cryoglobulinemia, SLE, hepatitis B infec-tion, subacute bacterial infection (SBE), and infected ventriculo-peritoneal shunt (VP shunt). Type II MPGN is also called dense-deposit disease due to the presence of continuous dense, ribbonlike mate-rial in the subendothelial area, tubules, and Bowman’s capsule. Although C3 has been detected on immunofluorescence, no immune complexes have been demon-strated. Its high recurrence after kidney transplantation suggests that a circulating factor is present. This factor was previously identified as a circulating C3 nephritic fac-tor (C3NeF), an IgG autoantibody against the alternative complement pathway C3 convertase that normally cleaves C3 into C3a and C3b. This binding to the enzyme creates a stable C3bBb complex that is resistant to enzymatic inactivation but allows consumption of C3. The exact role of C3NeF remains to be defined because it does not correlate with the activity of the disease. It is proposed that persistent hypocomplementemia and accumulation of terminal C5b-9 complement complex deposits in the glomeruli will eventually cause tissue damage. Type III MPGN is characterized by marked thickening of and disruption of the GBM. Subepithe-lial deposits are found that are suggestive of immune complexes. Causes of type III MPGN are unknown. A report links a gene that causes familial MPGN type III in an Irish family to chromosome 1.

The clinical course of MPGN varies according to the type and etiology. Type I MPGN has the best prognosis and appears to respond to steroids. Treatment of the underlying disease with antiviral agents (for hepatitis B and C) and antibacterial agents (for SBE and infected VP shunt) is effective in stabilizing renal function. Use of antiplatelet agents has limited use.