Membranous Glomerulonephritis

Membranous GN is characterised by widespread thickening of

the glomerular capillary wall and is the most common cause of

nephrotic syndrome in adults. In majority of cases (85%),

membranous GN is truly idiopathic, while in about 15% of cases

it is secondary to an underlying condition (e.g. SLE, malignancies,

infections such as chronic hepatitis B and C, syphilis, malaria,

and drugs).

ETIOPATHOGENESIS

Idiopathic membranous GN is an immune complex disease. Th e

deposits of immune complex are formed locally because

circulating immune complexes are detected in less than a

quarter of cases. Since leucocytic

infiltration is not a feature of membranous GN, damage to the

GBM is mediated directly by complement. While nephritogenic

antigen against which autoantibodies are formed in idiopathic

membranous GN is not known yet, the antigen in cases of

secondary membranous GN is either an endogenous (e.g.

DNA in SLE) or exogenous one (e.g. hepatitis B virus, tumour

antigen, treponema antigen, drug therapy with penicillamine).

Currently, pathogenesis of membrane alteration in membranous

GN is believed to be by MAC (membrane attack complex i.e.

C35b-C9) terminal complex on podocytes.

Morphologic Features

Grossly, the kidneys are enlarged, pale and smooth. Light

microscopy shows the following findings:

a. Glomeruli The characteristic finding is diffuse thickening of

glomerular capillary walls with all glomeruli being affected

more or less uniformly. As disease progresses, the deposits

are incorporated into enormously thickened basement

membrane, producing ‘duplication’ of GBM which is actually

formation of a new basement membrane. These basement

membrane changes are best appreciated by silver

impregnation stains (black colour) or by periodic acid-Schiff

stain (pink colour). Th ere is no cellular proliferation in the

glomerular tufts.
 b. Tubules: The renal tubules remain normal except in the

early stage when lipid vacuolation of the proximal convoluted

tubules may be seen.

c. Interstitium: Interstitium may show fine fibrosis and

scanty chronic inflammatory cells.

d. Vessels: In early stage, vascular changes are not prominent,

while later hypertensive changes of arterioles may occur.

Electron microscopy shows characteristic electron-dense

deposits in subepithelial location. The basement membrane

material protrudes between deposits as ‘spikes’.

Immunofluorescence microscopy reveals granular deposits of

immune complexes consisting of IgG associated with

complement C3. In secondary cases of membranous GN the

relevant antigen such as hepatitis B or tumour antigen may be

seen.

Clinical Features
The presentation in majority of cases is insidious onset of

nephrotic syndrome in an adult. The proteinuria is usually of

non-selective type. In addition, microscopic haematuria and

hypertension may be present

at the onset or may develop during the course of the disease.

The changes in membranous GN are irreversible in majority of

patients. Progression to impaired renal function and end stage

renal disease with progressive azotaemia occurs in

approximately 50% cases within a span of 2 to 20 years. Renal

vein thrombosis has been found to develop in patients with

membranous GN due to hypercoagulability. The role and

beneficial effects of steroid therapy with or without the

addition of immunosuppressive drugs is debatable.