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 (http://www.nejm.org/doi/full/10.1056/NEJMoa1409354). 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.

Check out more of eAJKD’s coverage of Kidney Week 2014! Also, follow @eAJKD on Twitter for live updates!

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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