Elsevier

Seminars in Nephrology

Volume 30, Issue 6, November 2010, Pages 635-644
Seminars in Nephrology

Membranous Nephropathy and Malignancy

https://doi.org/10.1016/j.semnephrol.2010.09.011Get rights and content

Summary

An association between the glomerular disease membranous nephropathy (MN) and malignancy has long been appreciated, but evidence supporting this relationship remains limited, speculative, and, at times, controversial. Reports that the two disease processes often evolve in parallel, as well as the occasional findings of tumor antigens or tumor-reactive antibodies within glomerular immune deposits, are all supportive of an association. However, the diagnosis of both MN and malignancy in the same individual also may be coincidental, especially in an older demographic group in which both diseases tend to occur. This article briefly reviews the proposed pathogenetic mechanisms of idiopathic and secondary forms of MN, as well as the arguments for and against the contention that malignancy-associated MN is itself a distinct clinical entity. In addition, the recent identification of the M-type phospholipase A2 receptor as a major glomerular antigen in idiopathic MN has the potential to offer fresh tools that might help resolve some of the controversy, and ultimately aid in the decision of how aggressively to screen for malignancy in an individual diagnosed with MN.

Section snippets

Proposed Pathogenesis of Idiopathic and Secondary Forms of MN

MN is not a single entity, but rather a common histopathologic pattern of injury caused by several disparate underlying disorders. Common to all are the immune deposits that form in a predominantly subepithelial location, beneath the foot processes of the visceral glomerular epithelial cell, or podocyte. The precise origin of these deposits has been the topic of much research in the past 50 years. Early work suggested that these deposits were the result of circulating immune complexes (CICs) of

Malignancy-Associated MN: A Distinct Entity?

With this background in hand, let us review the reasons why a causal relationship between malignancy and MN has not been universally accepted. Evidence for such an association was presented as early as 1966, when Lee et al1 observed that solid tumors had been found in 11% of cases of otherwise idiopathic nephrotic syndrome. Similar reports have followed on a regular basis,2, 3, 4, 5, 6, 7, 8, 9 each attempting to bring further clarity to the topic. One major argument against a causal

Recommendations

Despite the limitations noted earlier, the epidemiologic and serologic evidence for a true association of malignancy with MN is not to be ignored, especially because it has appeared time and time again, and has never convincingly been refuted. Given this suggestive relationship, and because of the risks associated with missing the diagnosis of a malignant tumor, many have recommended screening for common cancers in older patients with newly diagnosed MN without any other obvious cause. Because

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    • Cited by (0)

    Supported in part by a career development grant from the Halpin Foundation—American Society of Nephrology.

    Dr. Beck reports being a co-inventor on the patent application “Diagnostics for Membranous Nephropathy.”

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