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Relatively normal appearing glomeruli

Membranous nephropathy may show glomeruli which upon first glance appear relatively normal. This finding is most often seen in stage I disease.

By stage II disease, membranous nephropathy often shows uniformly thickened glomerular basement membranes. Other alterations such as hypercellularity and mesangial sclerosis are absent.

This glomerular tuft shows subtle thickening of the basement membranes, with patent capillary loops and no increase in sclerosis.

Silver stain highlight negatively staining "holes", indicative of membranous nephropathy

Silver stain highlights well-developed subepithelial spikes distributed regularly along the glomerular basement membrane.

Strong IgG immunofluorescence highlights the glomerular basement membranes

The IgG shows a granular staining pattern of regularly distributed deposits. This is differentiated from the linear pattern seen in anti-GBM disease.

Ultrastructural exam shows regularly distributed electron dense deposits. They are present on the subepithelial side of the basement membrane.

An area of mesangium (just right of center) shows paramesangial and mesangial deposits as well. This finding is more compatible with secondary membranous nephropathy.

Tubuloreticular inclusions are easily identified, which is indicative of a secondary etiology for the nephropathy. By far the most common cause would be underlying lupus erythematosis. This finding would be supported by finding co-deposits in the mesangium, another finding that is not typical for primary membranous nephropathy.


Membranous nephropathy (MN), also known as membranous glomerulopathy, is the most common cause of nephrotic syndrome in adults. It is a chronic immune complex disease that is either idiopathic (85%) or due to known secondary causes (15%).

In the idiopathic form, an antigen (not yet identified in humans) native to the basal surface of the podocytes is targeted by immunoglobulins. This leads to accumulation of subepithelial deposits on the basement membrane. In secondary MN, antigens of endogenous or exogenous origin. Endogenous antigens include SLE autoantigen-antibody complexes, tumors (especially lung, colon and melanoma) and thyroid antigens. Exogenous antigens include epitopes on certain drugs (e.g. penicillamine, NSAIDS) or infectious agents (e.g. hepatitis B, Treponema). These antigen will complex with antibodies, also leading to deposits in the subepithelial basement membrane.

These immunoglobulin deposits eventually elicit basement membrane thickening, and the basement membrane grows up and around the deposits, creating the typical spiking of the basement membrane highlighted using a silver stain. On immunofluroscence, the deposits of IgG and variable amounts of C3 created a granular pattern.


MN is the most frequent cause of nephrotic syndrome in adults, but is an uncommon cause of nephrotic syndrome in children. Current figures indicate that 30-40% of nephrotic syndrome is caused by MN versus only 5% of nephrotic syndrome in children.

Patients present with a slow onset of proteinuria. 15-35% present with hematuria and hypertension.


Treat the underlying condition if applicable. Otherwise, the efficacy of steroids and immunosuppressants is debatable. In contrast to minimal change disease, the proteinuria of MN is non-selective and does not respond to corticosteroids.1


Prognosis is rather good for idiopathic MN. In terms of the natural course of the disease (untreated disease), spontaneous remission occurs in ~5-30% of patients at 5 years. Spontaneous partial remission (defined as less than 2 grams of proteinuria per day) occurs in 25-40% of patients at 5 years. End-stage renal disease occurs in ~14% at 5 years, 35% at 10 years and 41% at 15 years.2

Factors that predict poorer prognosis include: severe proteinuria, advanced tubulointerstitial changes (inflammation, fibrosis) at biopsy and increased serum creatinine at presentation. In secondary MN, the prognosis would depend on the secondary cause.


1 Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th Ed. Philadelphia, PA: Elsevier; 2005: 979-81.

2 Cattran DC. Treatment of idiopathic membranous nephropathy. UpToDate: Topic last updated June 12, 2009.

Last updated: 2009-09-10
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