Membranoproliferative Glomerulonephritis (MPGN)

Membranoproliferative GN is another important cause of

nephrotic syndrome in children and young adults. As the name

implies, it is characterised by two histologic features—increase

in cellularity of the mesangium associated with increased

lobulation of the tuft, and irregular thickening of the capillary

wall.

ETIOPATHOGENESIS

Etiology of MPGN is unknown though in some cases there is

evidence of preceding streptococcal infection. Based on

ultrastructural, immunofluorescence and pathogenetic

mechanisms, three types of MPGN are recognised:

 Type I or classic form is an example of immune complex

disease and comprises more than 70% cases. It is

characterised by immune deposits in the subendothelial

position. Immune complex MPGN is seen in association with

systemic immune complex diseases (e.g. SLE, mixed

 cryoglobulinemia, Sjögren’s syndrome), chronic infections

(e.g. bacterial endocarditis, HIV, hepatitis B and C) and

malignancies (e.g. lymphomas and leukaemias).

 Type II or dense deposit disease is the example of

alternate pathway disease and constitutes about 30% cases.

Th e capillary wall thickening is due to the deposition of

electron-dense material in the lamina densa of the GBM.

Type II MPGN is an autoimmune disease in which patients

have IgG autoantibody termed C3 nephritic factor. Type II

cases have an association with partial lipodystrophy, an

unusual condition of unknown pathogenesis characterised by

symmetrical loss of subcutaneous fat from the upper half of

the body.

 Type III is rare and shows features of type I MPGN and

membranous nephropathy in association with systemic

diseases or drugs.

Morphological Features
Grossly, the kidneys are usually pale in appearance and firm in

consistency.

By light microscopy, the features are as under:

a. Glomeruli: Glomeruli show highly characteristic changes.

They are enlarged with accentuated lobular pattern. The

enlargement is due to variable degree of mesangial cellular

proliferation and increase in mesangial matrix. The GBM is

considerably thickened; with silver stains it shows two

basement membranes with a clear zone between them. This

 is commonly referred to as ‘double contour’, splitting, or

‘tram track’ appearance.

b. Tubules Tubular cells may show vacuolation and hyaline

droplets.

c. Interstitium Th ere may be scattered chronic inflammatory

cells and some finely granular foam cells in the interstitium.

d. Vessels Hypertensive vascular changes are prominent in

cases in which hypertension develops.

By electron microscopy and immunofluorescence

microscopy,the changes are different in the three types of

MPGN
Type I: It shows electron-dense deposits in subendothelial

location conforming to immune-complex character of the

disease. These deposits reveal positive fluorescence for C3 and

slightly fainter staining for IgG.

Type II: The hallmark of type II MPGN is the presence of

dense amorphous deposits within the lamina densa of the GBM

and in the mesangium. Immuno fluorescence studies reveal the

universal presence of C3 and properdin in the deposits but the

immuno globulins are usually absent

Type III: This rare form has electron-dense deposits within

the GBM as well as in subendothelial and sub epithelial regions

of the GBM. Immuno fluorescence studies show the presence of

C3, IgG and IgM.

CLINICAL FEATURES

Clinically, there are many similarities between the main forms

of MPGN. The most common age at diagnosis is between 15 and

20 years. Approximately 50% of the patients present with

nephrotic syndrome; about 30% have asymptomatic proteinuria;

and 20% have nephritic syndrome at presentation. Th e

proteinuria is non-selective. Haematuria and hypertension are

frequently present. Hypocomplementemia is a common feature.

With time, majority of patients progress to renal failure, while

some continue to have proteinuria, haematuria and hyper tension

with stable renal function. Prognosis of type I is relatively

better and majority of

patients survive without clinically significant impairment of GFR,

while type II cases run a variable clinical course.