Kidney Week 2014: Membranous Nephropathy

In the Friday November 14th 2014 session “Primary and Secondary Membranous Nephropathy”, Dr. Heather Reich from Toronto General Hospital talked about the value of the anti-phospholipase A2 receptor (anti-PLA2R) antibodies in discerning primary vs. secondary membranous nephropathy. She broke up the numbers: 25% of all membranous nephropathy is secondary, and 75% is primary. From the subset of primary membranous, the responsible antigen had been identified in ¾ of patients as the anti-PLA2R antibodies and ¼ have not been identified — although the latest online issue of NEJM describes the identification of thrombospondin type 1 as one of these potential previously unidentified antigens ( The epitope for Anti-PLA2R antibody is located in the N-terminal domain in 90% of the cases. However, despite the early excitement, there are some issues with anti-PLA2R antibodies: there is a percentage of patients with secondary membranous that have a positive antibody titer, most of the studies comparing anti-PLA2R in primary vs. secondary are small, serum and biopsy staining for anti-PLA2R can dissociate (e.g., positive biopsy staining and negative serum antibody). Therefore, the anti-PLA2R antibodies are not ready for primetime. Dr. Richard Glassock, professor emeritus at UCLA, then talked about membranous nephropathy and malignancy. Patients with primary membranous usually had 2 age peaks: 30-40 and 50-60 y/o. In contrast, secondary membranous patients from malignancy are usually older (65-78, average 73 y/o) and are heavy smokers. 80% of cancers in secondary membranous are carcinomas and a study showed that lung cancer is the most common type. Glassock’s criteria for patients with high suspicious for secondary membranous from cancer are: age > 50 y/o, smokers, family history of cancer, lab features such as hypercalcemia and anemia, and on biopsy: absence of PLA2R epitope expression, non-IgG4 subclass, and > 8 WBC in glomerulus. He recommends screening all the smokers with CT chest and, in general, repeat surveillance screening if done more than 1 year ago (e.g. repeat mammogram older than 1 year ago). Finally, Dr. Michael Choi, from John Hopkins, talked about treatment for membranous. First line therapy is Ponticelli protocol (IV methylprednisolone daily for 3 days on months 1, 3, and 5 followed by oral prednisone, and oral cyclophosphamide daily for a month on months 2, 4, and 6), second-line therapy is calcineurin inhibitors (CNI). A head-to-head trial comparing Ponticelli protocol with CNI showed that 20% decline in CrCl and proteinuria reduction were better with Ponticelli protocol. Third-line therapy is rituximab. Rituximab effects are beyond B cell depletion and its effects do not correlate with it. Apparently, it also causes reduction of a protein SMPDL3B and directly stabilizes actin in the podocytes. The fourth-line therapy is ACTH gel, although he mentioned that synthetic ACTH IV has been also shown to decrease proteinuria in naïve patients.

Post written by Dr. Helbert Rondon, eAJKD Contributor.

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2 Comments on Kidney Week 2014: Membranous Nephropathy

  1. Should we first rule out malignancy in adults > 50 years and then decide on anti proteinuric drugs or we start with ACE inhibitors straight away ?

  2. Helbert Rondon, MD // June 12, 2015 at 10:27 am // Reply

    Thanks for the comments. Usually one would do both simultaneously. Start an ACEI is a general therapy for proteinuria which would benefit even if membranous nephropathy turn out to be secondary in nature (e.g. malignancy).

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