Membranous Glomerulopathy: the Evolving Story

Purpose Of Review: Membranous nephropathy is one of the most common glomerulopathies. Current treatments are entirely empirical, and pathophysiology-driven therapies are dramatically lacking. This review focuses on new pathophysiologic aspects of the disease, with special emphasis on the antigenic targets of pathogenic antibodies.

Recent Findings: In the past few years, two major antigens have been identified in human membranous nephropathy. The first is neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of membranous nephropathy that occur in newborns from NEP-deficient mothers. The second is the M-type phospholipase A2 receptor (PLA2R), the first autoantigen identified in idiopathic membranous nephropathy in the adult.

Summary: A common denominator shared by most cases of membranous nephropathy is the expression by podocytes of antigenic targets for in-situ formation of glomerular immune deposits. The recent discovery of neutral endopeptidase and PLA2R provides new tools for the monitoring of disease activity and should be of value in designing new antigen-driven therapeutic strategies.