Glomerulonephritis: Antibody Mediated Injury

Membranoproliferative Glomerulonephritis

Peer Review Status: Internally reviewed

Membranoproliferative, or mesangiocapillary, glomerulonephritis (MPGN) is a chronic progressive glomerulonephritis that occurs in older children and adults.

Circulating immune complexes have been identified in 50% of patients and activation of the complement system with hypocomplementemia, is a hallmark of MPGN.

Idiopathic MPGN has several distinct histopathologic and immunopathologic features and three variants have been described.

• Type I MPGN characterized by mesangial and subendothelial immune deposits.
• Type II MPGN (dense deposit disease) characterized by interrupted linear deposits in the lamina densa of the basement membrane.
• Type III MPGN, an uncommon variant, characterized by features of both type I MPGN and membranous GN, or by disurption of the glomerular basement membrane with accumulation of new basement membrane material arranged in layers.

A. Morphologic Features
All types of MPGN feature mesangial hypercellularity and matrix expansion, and mesangial interposition beneath the endothelium with formation of double contours.

In type I MPGN the deposits are subendothelial and mesangial.

The glomeruli frequently contain C3 and immunoglobulins,

and ultrastructurally the electron dense deposits are subendothelial with mesangial interposition and basement membrane duplication.

In type II MPGN or dense deposit disease, electron dense deposits are present within the lamina densa of the glomerular basement membrane

and contain C3 in a linear pattern in the peripheral capillary loops with ring-like patterns in the mesangium

In type III MPGN the deposits are subendothelial and subepithelial. The deposits are usually large and span the glomerular basement membrane.

B. Clinical Course
Patients with MPGN may present with the nephrotic syndrome, an abnormal urinary sediment with non-nephrotic proteinuria or with acute nephritis. The diagnosis is suspected when serum complement levels are depressed.

Type I MPGN:

• is the most frequent primary MPGN
• is also often associated with systemic disease, infection and neoplasms.
• Membranoproliferative glomerulonephritis secondary to cyroglobulinemia is strongly associated with Hepatitis C virus infection.
• The nephrotic syndrome is the most common presenting illness.

Type I MPGN is a slowly progressive disease; in 30-40% of patients the disease remains stable despite persistent nephrotic range proteinuria. Median survival, free of renal failure in both children and adults ranges from 9 to 12 years.

In type II MPGN:

• Acute nephritis or recurrent macroscopic hematuria are the most common presentations.
• Most patients with type II MPGN are younger than 20 years of age, have more persistent C3 depression and more commonly present with nephritis.
• Approximately 20% of patients remain stable for many years and median survival, free of renal failure ranges from 5 to 10 years.

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Last Modified: February 26, 1997