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In chronic kidney disease (CKD), circulating FGF23 and PTH concentrations progressively increase as renal function declines. Oxidation of PTH at two methionine residues (positions 8 and 18) causes a loss of function. The impact of n\u2010oxPTH and oxPTH on FGF23 synthesis, however, and how n\u2010oxPTH and oxPTH concentrations are affected by CKD, is yet unknown. The effects of oxidized and non\u2010oxidized PTH 1\u201034 on\n                    <jats:italic>Fgf23<\/jats:italic>\n                    gene expression were analyzed in UMR106 osteoblast\u2010like cells. Furthermore, we investigated the relationship between n\u2010oxPTH and oxPTH, respectively, with FGF23 in two independent patients' cohorts (620 children with CKD and 600 kidney transplant recipients). While n\u2010oxPTH stimulated\n                    <jats:italic>Fgf23<\/jats:italic>\n                    mRNA synthesis in vitro, oxidation of PTH in particular at Met8 led to a markedly weaker stimulation of\n                    <jats:italic>Fgf23<\/jats:italic>\n                    . The effect was even stronger when both Met8 and Met18 were oxidized. In both clinical cohorts, n\u2010oxPTH\u2014but not oxPTH\u2014was significantly associated with FGF23 concentrations, independent of known confounding factors. Moreover, with progressive deterioration of kidney function, intact PTH (iPTH) and oxPTH increased substantially, whereas n\u2010oxPTH increased only moderately. In conclusion, n\u2010oxPTH, but not oxPTH, stimulates\n                    <jats:italic>Fgf23<\/jats:italic>\n                    gene expression. The increase in PTH with decreasing GFR is mainly due to an increase in oxPTH in more advanced stages of CKD.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000596r","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T02:41:23Z","timestamp":1600828883000},"page":"15269-15281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Relationship between GFR, intact PTH, oxidized PTH, non\u2010oxidized PTH as well as FGF23 in patients with CKD"],"prefix":"10.1096","volume":"34","author":[{"given":"Shufei","family":"Zeng","sequence":"first","affiliation":[{"name":"Fifth Department of Medicine (Nephrology\/Endocrinology\/Rheumatology) University Medical Centre Mannheim University of Heidelberg Heidelberg Germany"},{"name":"Department of Nephrology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Querfeld","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Nephrology and Metabolic Diseases Department of Pediatrics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Feger","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Hohenheim Stuttgart Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dieter","family":"Haffner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver and Metabolic Diseases Pediatric Research Center Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed A.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Fifth Department of Medicine (Nephrology\/Endocrinology\/Rheumatology) University Medical Centre Mannheim University of Heidelberg Heidelberg Germany"},{"name":"Institute of Nutritional Science University of Potsdam Potsdam Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Chu","sequence":"additional","affiliation":[{"name":"Fifth Department of Medicine (Nephrology\/Endocrinology\/Rheumatology) University Medical Centre Mannheim University of Heidelberg Heidelberg Germany"},{"name":"Department of Nephrology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"Slowinski","sequence":"additional","affiliation":[{"name":"Department of Nephrology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Bernd Dschietzig","sequence":"additional","affiliation":[{"name":"Department of Cardiology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Center for Pediatrics and Adolescent Medicine University of Heidelberg Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingquan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Fifth Department of Medicine (Nephrology\/Endocrinology\/Rheumatology) University Medical Centre Mannheim University of Heidelberg Heidelberg Germany"},{"name":"Institute of Nutritional Science University of Potsdam Potsdam Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Physiology University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"College of Life Science and Technology Heilongjiang Bayi Agricultural University Daqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Rausch","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Hohenheim Stuttgart Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina","family":"Horvathova","sequence":"additional","affiliation":[{"name":"Biomedica Slovakia s.r.o. 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