Exciting NEJM Membranous Nephropathy Article

A landmark paper on membranous nephropathy was published by Beck et al in the most recent issue of NEJM. Ultimately we will have to see if the finding is reproducible, but based on the data presented this represents a major breakthrough in understanding the pathogenesis of membranous nephropathy and nephrotic syndrome.

There has long been strong evidence in support of a circulating factor which causes podocyte injury and resultant nephrotic syndrome. Additional evidence from the neutral endopeptidase story further suggested that an autoantibody directed again some podocyte antigen might be the culprit. In this issue, the researchers demonstrate that in 70% of patients with idiopathic membranous nephropathy (but 0% of patients with secondary membranous nephropathy or other forms of proteinuric kidney disease such as FSGS or diabetic nephropathy) contain an autoantibody against the podocyte antigen phospholipase A2 receptor. Furthermore, the autoantibody's presence appears to correlate with disease activity, suggesting a possible pathogenic role.

The work has a number of implications. First, it suggests that membranous nephropathy is indeed a separate disease than FSGS and other distinct forms of nephrotic syndrome. The common final pathway for proteinuria is the same (podocyte injury), but the ways in which to get there is likely different. Second, it suggests that detection of serum antibodies against phospholipase A2 receptor may be a useful part of the diagnostic workup for nephrotic syndrome--perhaps even making biopsies unnecessary--and perhaps could be used to follow disease activity in response to various therapeutic maneuvers. That is, this test may well become the "ANCA" of membranous nephropathy.