{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:20:29Z","timestamp":1788283229590,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Background:<\/jats:title>\n Peritoneal dialysis (PD) is a life-sustaining therapy for kidney failure, yet its long-term viability is compromised by progressive peritoneal fibrosis in some patients. Currently, reliable treatment options are lacking as the pathogenesis remains poorly understood, with the metabolic underpinnings of fibrotic progression remaining particularly elusive.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Using a physiologically relevant framework comprising human primary mesothelial cells and a PD fluid\u2013exposed mouse model, we performed bidirectional genetic and pharmacological modulation of branched-chain amino acid catabolism. Integrated proteomic and metabolomic analyses were conducted to investigate downstream metabolic consequences.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n We identified profound impairment in branched-chain amino acid (BCAA) catabolism, centered on a functional bottleneck at the rate-limiting branched-chain \u03b1-ketoacid dehydrogenase complex, as a metabolic hallmark of peritoneal fibrosis. Functional uncoupling of the amino acids from their ketoacid derivatives indicated that branched-chain \u03b1-ketoacid (BCKA) burden was more closely linked to the fibrotic phenotype than BCAA abundance alone. Mechanistically, BCKA burden was associated with reduced glucose-6-phosphate dehydrogenase expression and activity, lower NADPH-generating capacity, and increased intracellular oxidant burden.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Together, these findings showed that BCKA burden, rather than BCAA abundance alone, more closely tracked fibrotic responses and was linked to reduced pentose phosphate pathway\u2013associated redox capacity in peritoneal fibrosis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001241","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:00:45Z","timestamp":1788282045000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Impaired BCAA Catabolism Drives Peritoneal Fibrosis via BCKA-Mediated Suppression of the Pentose Phosphate Pathway"],"prefix":"10.1681","author":[{"given":"Jiayang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Minhang Hospital, Fudan University, Shanghai 201203, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiangang","family":"Wu","sequence":"additional","affiliation":[{"name":"Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9579-4524","authenticated-orcid":false,"given":"Junhao","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Minhang Hospital, Fudan University, Shanghai 201203, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-1239","authenticated-orcid":false,"given":"Svetlana","family":"Reilly","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1670-1922","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Minhang Hospital, Fudan University, Shanghai 201203, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Minhang Hospital, Fudan University, Shanghai 201203, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-4217","authenticated-orcid":false,"given":"Hong","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Minhang Hospital, Fudan University, Shanghai 201203, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4710-4571","authenticated-orcid":false,"given":"Nan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-023X","authenticated-orcid":false,"given":"Zhiping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China."},{"name":"Department of Clinical Pharmacy, Kunshan Women and Children's Healthcare Hospital, Children\u2019s Hospital of Fudan University Kunshan Branch, Kunshan 215301, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-1405","authenticated-orcid":false,"given":"Zanzhe","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Ren Ji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3251-5037","authenticated-orcid":false,"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Minhang Hospital, Fudan University, Shanghai 201203, China."},{"name":"Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,9,1]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:00:45Z","timestamp":1788282045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001241","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-03-23","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}