Complementary and alternative medicine-associated membranous nephropathy: a systematic review

Background: Complementary and alternative medicine use can lead to the development of membranous nephropathy (MN). The true prevalence and etiologies of complementary and alternative medicine-induced MN remain likely underestimated. The purpose of this review was to report on the incidence of MN induced by various types of complementary and alternative medicine, their clinical presentation, and treatment responses. Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. We performed searches in MEDLINE, Embase, PubMed, the Cochrane Library, and conducted hand searches of the reference lists. Studies reporting cases of membranous nephropathy with complementary and alternative medicine exposure published in English from 2010 were included. Two authors independently assessed study eligibility and extracted data for analysis. Results: Twenty-seven studies were included (case reports [n = 10], case series [n = 10], cohort studies [n = 5], and case-control studies [n = 2]) involving a total of 262 patients (66% female) with biopsy-proven MN. The mean age of patients was 43 (±14) years, and the majority of cases (70 [87.5%]) reported exposure to mercury from traditional medicines, skin-whitening creams and hair dyes. Of the 113 cases tested for neural epidermal growth factor-like 1 protein (NELL-1) antibodies, 107 (94.7%) were positive. Treatment approaches varied widely. Of those managed conservatively (54.8%), 64% achieved complete remission and 24% achieved partial remission. Conclusions: Most reported cases of complementary and alternative medicine-associated MN were in the context of mercury exposure and tested positive for NELL-1. There was no difference in clinical response between those treated with immunosuppression or conservative management.