{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:48:51Z","timestamp":1783745331867,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["451001034"],"award-info":[{"award-number":["451001034"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FortaFoundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Primary focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury and treatment-resistant nephrotic syndrome. Recurrence of the original disease after kidney transplantation (rFSGS) occurs in 10%\u201350% of patients. Unidentified circulating permeability factors (CPF) are likely involved in FSGS pathogenesis. We hypothesized that donor podocyte susceptibility to CPF is also relevant. We developed a personalized model for (r)FSGS using induced pluripotent stem cell (iPSC)-derived podocytes from patients and kidney donors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Five patients and their respective living kidney donors were included. Three patients had developed rFSGS, and two patients manifested no symptoms of rFSGS. One patient (P5) had heterozygous mutations in NPHS2. Peripheral blood mononuclear cells were reprogrammed to iPSC, and differentiated to podocytes. iPSC-derived podocytes from either patients or donors were exposed to presumed CPF-containing plasma\/serum of corresponding patients. Three assays to detect podocyte injury were performed: (i) reactive oxygen species formation, (ii) cellular granularity induction, and (iii) quantitative assessment of F-actin redistribution (FAR), a new quantitative method. Crossmatch experiments with donor iPSC-derived podocytes and patients samples assessed individual susceptibility to CPF-induced injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Successful podocyte differentiation was confirmed by morphology and protein expression. Only FAR differentiated consistently between patient and healthy donor samples. All pre-transplant patient samples except P5 caused significant FAR in corresponding patient podocytes. Significant FAR was observed in donor podocytes exposed to corresponding patient samples in the setting of rFSGS, and not in donor podocytes exposed to samples of patients who did not develop rFSGS. Effects of FSGS patient samples on non-corresponding donor podocytes were variable.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In vitro assays using iPSC-derived donor podocytes may allow individualized assessment of rFSGS. Prospective studies in a larger cohort are required to validate our findings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf045","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T07:45:20Z","timestamp":1740642320000},"page":"1736-1745","source":"Crossref","is-referenced-by-count":3,"title":["Personalized disease recurrence modeling using iPSC-derived podocytes in patients with idiopathic nephrotic syndrome"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-2181","authenticated-orcid":false,"given":"Bartholomeus T","family":"van den Berge","sequence":"first","affiliation":[{"name":"Radboudumc Department of Nephrology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]},{"name":"Radboudumc Department of Pathology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-9921","authenticated-orcid":false,"given":"Martijn","family":"van den Broek","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Pathology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]},{"name":"Radboudumc Department of Pediatric Nephrology, Radboud Institute for Molecular Life Science, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Di Giovanni","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Nephrology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Debiec","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Sorbonne Universit\u00e9 and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Gloudemans","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Pathology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinty","family":"Leusink","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Nephrology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"den Braanker","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Nephrology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack F M","family":"Wetzels","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Nephrology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-6900","authenticated-orcid":false,"given":"Pierre","family":"Ronco","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche Sorbonne Universit\u00e9 and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Smeets","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Pathology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitske","family":"Jansen","sequence":"additional","affiliation":[{"name":"Uniklinik RWTH Aachen Department for Renal and Hypertensive Diseases, Rheumatological and Immunological Diseases, , Aachen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-4916","authenticated-orcid":false,"given":"Rutger J","family":"Maas","sequence":"additional","affiliation":[{"name":"Radboudumc Department of Nephrology, Radboud Institute for Molecular Life Sciences, , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"2025082900421759000_bib1","doi-asserted-by":"publisher","first-page":"502","DOI":"10.2215\/CJN.05960616","article-title":"Focal segmental glomerulosclerosis","volume":"12","author":"Rosenberg","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025082900421759000_bib2","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1159\/000508099","article-title":"Focal segmental glomerulosclerosis: state-of-the-art and clinical perspective","volume":"144","author":"Shabaka","year":"2020","journal-title":"Nephron"},{"key":"2025082900421759000_bib3","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1093\/ndt\/gfae025","article-title":"Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group","volume":"39","author":"Mirioglu","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2025082900421759000_bib4","doi-asserted-by":"publisher","first-page":"e14970","DOI":"10.1111\/ctr.14970","article-title":"Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation","volume":"37","author":"Chukwu","year":"2023","journal-title":"Clin Transplant"},{"key":"2025082900421759000_bib5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.2215\/CJN.08970719","article-title":"Recurrence of FSGS after kidney transplantation in adults","volume":"15","author":"Uffing","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025082900421759000_bib6","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.kint.2023.10.017","article-title":"Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements","volume":"105","author":"Raina","year":"2024","journal-title":"Kidney Int"},{"key":"2025082900421759000_bib7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1471-2369-14-47","article-title":"A retrospective study of focal segmental glomerulosclerosis: clinical criteria can identify patients at high risk for recurrent disease after first renal transplantation","volume":"14","author":"Maas","year":"2013","journal-title":"BMC Nephrol"},{"key":"2025082900421759000_bib8","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1097\/00007890-199601270-00012","article-title":"The influence of native nephrectomy on the incidence of recurrent disease following renal transplantation for primary glomerulonephritis","volume":"61","author":"Odorico","year":"1996","journal-title":"Transplantation"},{"key":"2025082900421759000_bib9","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1681\/ASN.2013080852","article-title":"Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence","volume":"25","author":"Ding","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"2025082900421759000_bib10","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1007\/s00467-018-3994-3","article-title":"Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings","volume":"33","author":"Pelletier","year":"2018","journal-title":"Pediatr Nephrol"},{"key":"2025082900421759000_bib11","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1093\/ndt\/gfae108","article-title":"Prophylactic treatment of FSGS recurrence in patients who relapsed in a previous kidney graft","volume":"40","author":"Uro-Coste","year":"2025","journal-title":"Nephrol Dial Transplant"},{"key":"2025082900421759000_bib12","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1056\/NEJMoa2314471","article-title":"Autoantibodies targeting nephrin in podocytopathies","volume":"391","author":"Hengel","year":"2024","journal-title":"N Engl J Med"},{"key":"2025082900421759000_bib13","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1093\/ndt\/gfu355","article-title":"Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future","volume":"29","author":"Maas","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"2025082900421759000_bib14","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.kint.2018.10.030","article-title":"Development of a novel cell-based assay to diagnose recurrent focal segmental glomerulosclerosis patients","volume":"95","author":"Srivastava","year":"2019","journal-title":"Kidney Int"},{"key":"2025082900421759000_bib15","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1007\/s00467-012-2163-3","article-title":"TNFalpha pathway blockade ameliorates toxic effects of FSGS plasma on podocyte cytoskeleton and beta3 integrin activation","volume":"27","author":"Bitzan","year":"2012","journal-title":"Pediatr Nephrol"},{"key":"2025082900421759000_bib16","doi-asserted-by":"publisher","first-page":"85ra46","DOI":"10.1126\/scitranslmed.3002231","article-title":"Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis","volume":"3","author":"Fornoni","year":"2011","journal-title":"Sci Transl Med"},{"key":"2025082900421759000_bib17","doi-asserted-by":"publisher","first-page":"F1148","DOI":"10.1152\/ajprenal.00349.2015","article-title":"Novel unbiased assay for circulating podocyte-toxic factors associated with recurrent focal segmental glomerulosclerosis","volume":"310","author":"Kachurina","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"2025082900421759000_bib18","doi-asserted-by":"publisher","first-page":"e0203869","DOI":"10.1371\/journal.pone.0203869","article-title":"Differentiation of human iPSCs into functional podocytes","volume":"13","author":"Rauch","year":"2018","journal-title":"PLoS One"},{"key":"2025082900421759000_bib19","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1038\/s41596-018-0007-8","article-title":"Directed differentiation of human induced pluripotent stem cells into mature kidney podocytes and establishment of a glomerulus chip","volume":"13","author":"Musah","year":"2018","journal-title":"Nat Protoc"},{"key":"2025082900421759000_bib20","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1093\/ndt\/gfaa211","article-title":"Novel in vitro assays to detect circulating permeability factor(s) in idiopathic focal segmental glomerulosclerosis","volume":"36","author":"den Braanker","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"2025082900421759000_bib21","doi-asserted-by":"publisher","first-page":"dev200198","DOI":"10.1242\/dev.200198","article-title":"Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling","volume":"149","author":"Jansen","year":"2022","journal-title":"Development"},{"key":"2025082900421759000_bib22","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1681\/ASN.V133630","article-title":"A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression","volume":"13","author":"Saleem","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"2025082900421759000_bib23","doi-asserted-by":"publisher","first-page":"3039","DOI":"10.3390\/biomedicines11113039","article-title":"Levamisole modulation of podocytes\u2019 actin cytoskeleton in nephrotic syndrome","volume":"11","author":"Veissi","year":"2023","journal-title":"Biomedicines"},{"key":"2025082900421759000_bib24","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1016\/j.ekir.2022.09.014","article-title":"Circulating permeability factors in focal segmental glomerulosclerosis: in v itro detection","volume":"7","author":"Veissi","year":"2022","journal-title":"Kidney Int Rep"},{"key":"2025082900421759000_bib25","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1111\/joa.13595","article-title":"Identification of multinucleated cells in human kidney cortex: a way for tissue repairing?","volume":"240","author":"Fantone","year":"2022","journal-title":"J Anat"},{"key":"2025082900421759000_bib26","doi-asserted-by":"publisher","first-page":"102139","DOI":"10.1016\/j.mex.2023.102139","article-title":"Corrigendum to \u201cA quantitative method to analyse F-actin distribution","volume":"10","author":"Zonderland","year":"2023","journal-title":"MethodsX"},{"key":"2025082900421759000_bib27","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/s41581-019-0217-5","article-title":"Molecular stratification of idiopathic nephrotic syndrome","volume":"15","author":"Saleem","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"2025082900421759000_bib28","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1007\/s00467-019-4203-8","article-title":"Nephrotic syndrome in a dish: recent developments in modeling in vitro","volume":"35","author":"Veissi","year":"2020","journal-title":"Pediatr Nephrol"},{"key":"2025082900421759000_bib29","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1038\/s42003-023-05203-4","article-title":"iPSC-derived type IV collagen alpha5-expressing kidney organoids model Alport syndrome","volume":"6","author":"Hirayama","year":"2023","journal-title":"Commun Biol"},{"key":"2025082900421759000_bib30","doi-asserted-by":"publisher","first-page":"4577","DOI":"10.1038\/s41598-021-83883-w","article-title":"Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis","volume":"11","author":"Muller-Deile","year":"2021","journal-title":"Sci Rep"},{"key":"2025082900421759000_bib31","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1681\/ASN.2004030172","article-title":"Nephrotic plasma alters slit diaphragm-dependent signaling and translocates nephrin, podocin, and CD2 associated protein in cultured human podocytes","volume":"16","author":"Coward","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"2025082900421759000_bib32","doi-asserted-by":"publisher","first-page":"21137","DOI":"10.1074\/jbc.M117.819029","article-title":"The Hippo pathway regulator KIBRA promotes podocyte injury by inhibiting YAP signaling and disrupting actin cytoskeletal dynamics","volume":"292","author":"Meliambro","year":"2017","journal-title":"J Biol Chem"},{"key":"2025082900421759000_bib33","doi-asserted-by":"publisher","first-page":"e165002","DOI":"10.1172\/jci.insight.165002","article-title":"KIBRA upregulation increases susceptibility to podocyte injury and glomerular disease progression","volume":"8","author":"Meliambro","year":"2023","journal-title":"JCI Insight"},{"key":"2025082900421759000_bib34","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.kint.2023.11.022","article-title":"A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence","volume":"105","author":"Shirai","year":"2024","journal-title":"Kidney Int"},{"key":"2025082900421759000_bib35","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1681\/ASN.2021060794","article-title":"Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology","volume":"33","author":"Watts","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"2025082900421759000_bib36","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.kint.2024.07.022","article-title":"Pre-transplant anti-nephrin antibodies are specific predictors of recurrent diffuse podocytopathy in the kidney allograft","volume":"106","author":"Batal","year":"2024","journal-title":"Kidney Int"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfaf045\/62208186\/gfaf045.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/40\/9\/1736\/62208186\/gfaf045.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/40\/9\/1736\/62208186\/gfaf045.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T04:42:25Z","timestamp":1756442545000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/40\/9\/1736\/8046456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,2,28]]},"published-print":{"date-parts":[[2025,8,29]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfaf045","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,2,28]]}}}