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Approximately 90% of cases are classified as idiopathic nephrotic syndrome, most of which are histologically diagnosed as minimal change disease (MCD). Although the majority of patients achieve remission with steroid therapy, a subset develops steroid resistance and progresses to focal segmental glomerulosclerosis (FSGS) and kidney failure. Increasing evidence suggests that MCD and idiopathic FSGS represent a disease continuum, with FSGS reflecting a more advanced stage. Although several candidates have been proposed as circulating factors, none fully explains the disease pathogenesis. This landscape changed in 2022 with the discovery of anti-nephrin autoantibodies in MCD. Subsequently, we reported that circulating anti-nephrin autoantibodies were identified by ELISA in patients with post-transplant recurrent FSGS, and punctate IgG deposition colocalizing with nephrin was consistently detected in allograft biopsy specimens obtained during recurrence. Notably, these IgG deposits resolved following remission. Collectively, these findings suggest diffuse podocytopathies as autoantibody-mediated disorders and support a shift toward autoantibody-based disease classification. Experimental and clinical studies demonstrate that anti-nephrin autoantibodies induce nephrin phosphorylation. This process may be associated with nephrin endocytosis and subsequent cytoskeletal alterations. Additionally, autoantibodies targeting slit diaphragm molecules other than nephrin have been identified. However, the pathogenic roles of these autoantibodies remain to be clarified. Collectively, these findings highlight a complex, autoantibody-driven mechanism in diffuse podocytopathies and underscore the need for standardized assays and biomarker-driven classification strategies.<\/jats:p>","DOI":"10.1007\/s10157-026-02830-z","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:57:19Z","timestamp":1772103439000},"page":"691-697","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-nephrin autoantibodies in post-transplant recurrent focal segmental glomerulosclerosis: diagnostic advances and future directions"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3734-4766","authenticated-orcid":false,"given":"Yoko","family":"Shirai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4309-8672","authenticated-orcid":false,"given":"Motoshi","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"issue":"4","key":"2830_CR1","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s10157-016-1319-z","volume":"21","author":"K Kikunaga","year":"2017","unstructured":"Kikunaga K, Ishikura K, Terano C, Sato M, Komaki F, Hamasaki Y, et al. 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