{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:29:06Z","timestamp":1791721746625,"version":"4.3.4"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Nazarbayev University Collaborative Research Program","award":["091019CRP2105"],"award-info":[{"award-number":["091019CRP2105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Proteinuria is a well-established biomarker of chronic kidney disease (CKD) and a risk predictor of associated disease outcomes. Proteinuria is also a driver of CKD progression toward end-stage kidney disease. Toxic effects of filtered proteins on proximal tubular epithelial cells enhance tubular atrophy and interstitial fibrosis. The extent of protein toxicity and the underlying molecular mechanisms responsible for tubular injury during proteinuria remain unclear. Nevertheless, albumin elicits its toxic effects when degraded and reabsorbed by proximal tubular epithelial cells. Overall, healthy kidneys excrete over 1000 individual proteins, which may be potentially harmful to proximal tubular epithelial cells when filtered and\/or reabsorbed in excess. Proteinuria can cause kidney damage, inflammation and fibrosis by increasing reactive oxygen species, autophagy dysfunction, lysosomal membrane permeabilization, endoplasmic reticulum stress and complement activation. Here we summarize toxic proteins reported in proteinuria and the current understanding of molecular mechanisms of toxicity of proteins on proximal tubular epithelial cells leading to CKD progression.<\/jats:p>","DOI":"10.1093\/ndt\/gfad215","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T04:10:13Z","timestamp":1696392613000},"page":"589-599","source":"Crossref","is-referenced-by-count":71,"title":["Tubular toxicity of proteinuria and the progression of chronic kidney disease"],"prefix":"10.1093","volume":"39","author":[{"given":"Zhalaliddin","family":"Makhammajanov","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine, Nazarbayev University , Astana , Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9844-8772","authenticated-orcid":false,"given":"Abduzhappar","family":"Gaipov","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Nazarbayev University , Astana , Kazakhstan"},{"name":"Clinical Academic Department of Internal Medicine, CF \u201cUniversity Medical Center\u201d , Astana , Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Askhat","family":"Myngbay","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University , Astana , Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rostislav","family":"Bukasov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Sciences and Humanities, Nazarbayev University , Astana , Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Aljofan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine, Nazarbayev University , Astana , Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-0675","authenticated-orcid":false,"given":"Mehmet","family":"Kanbay","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Koc University , Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"2024032707114482100_bib1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nrneph.2017.52","article-title":"The systemic nature of CKD","volume":"13","author":"Zoccali","year":"2017","journal-title":"Nat Rev Nephrol"},{"key":"2024032707114482100_bib2","doi-asserted-by":"crossref","first-page":"e0158765","DOI":"10.1371\/journal.pone.0158765","article-title":"Global prevalence of chronic kidney disease \u2013 a systematic review and meta-analysis","volume":"11","author":"Hill","year":"2016","journal-title":"PLoS 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