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Following renal transplantation, recurrence of FSGS (rFSGS) occurs in 30%\u201340% of patients with a high risk of graft loss. rFSGS typically presents with nephrotic-range proteinuria within days after post-transplantation. This review summarizes pathophysiology, biomarkers, and therapeutic strategies for rFSGS. Monogenic causes of FSGS, such as those caused by APOL1 mutation, show variable recurrence, while NPHS2 and ACTN4 show low recurrence of FSGS. Evidence suggests that idiopathic or primary FSGS is strongly associated with rFSGS, owing to podocyte structural damage caused by circulating permeability factors or immune dysfunction. Recent advances have identified biomarkers such as anti-nephrin antibodies, anti-CD40 antibodies, soluble tumor necrosis factor receptor 2 (sTNFR2), and soluble urokinase-type plasminogen activator receptor (suPAR) that help in early detection of recurrent FSGS. Post-transplant monitoring includes measuring urine protein-to-creatinine ratio (UPCR) and 24-h urine protein excretion, and a kidney biopsy. Preventive strategies, although including plasmapheresis and rituximab, show limited benefit and are not recommended for routine prophylaxis. Treatment options include plasmapheresis, immunoadsorption, and immunosuppressive drugs such as cyclophosphamide, rituximab, or calcineurin inhibitors. Recurrent FSGS is a clinical challenge with its multifactorial pathogenesis. Incorporating strategies such as genetic testing, risk stratification, and early detection with the help of biomarkers and early treatment can induce remission and preserve graft survival. Despite these advances, large prospective studies are still required for standardizing prevention and management strategies for rFSGS.<\/jats:p>","DOI":"10.1177\/09636897261417049","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:46:53Z","timestamp":1774860413000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Recurrence of focal segmental glomerulosclerosis: An updated review of pathophysiology, biomarkers, and therapeutic strategies"],"prefix":"10.1177","volume":"35","author":[{"given":"Zachary","family":"Oatley","sequence":"first","affiliation":[{"name":"College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Jaber","sequence":"additional","affiliation":[{"name":"College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Rayarakula","sequence":"additional","affiliation":[{"name":"College of Public Health, Kent State University, Kent, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Guirguis","sequence":"additional","affiliation":[{"name":"College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layth","family":"Khawaja","sequence":"additional","affiliation":[{"name":"College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Bhindwallam","sequence":"additional","affiliation":[{"name":"College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Gregorio Mara\u00f1\u00f3n Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime Manuel","family":"Restrepo","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Department, Fundaci\u00f3n Valle del Lili, Cali, Colombia"},{"name":"Universidad ICESI, Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupesh","family":"Raina","sequence":"additional","affiliation":[{"name":"College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA"},{"name":"Department of Nephrology, Akron Nephrology Associates\/Cleveland Clinic Akron General, Akron, OH, USA"},{"name":"Department of Nephrology, Akron Children\u2019s Hospital, Akron, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(04)01081-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.09.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2011.11.015"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017090958"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","unstructured":"Alejandro Tavera D\u00edaz M Andr\u00e9s Ballesteros Castro D Lafuente Covarrubias O Vannia Nava Rojas A. 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