Relationship between GFR, intact PTH, oxidized PTH, non‐oxidized PTH as well as FGF23 in patients with CKD. Issue 11 (22nd September 2020)

• Record Type: Journal Article
• Authors: Zeng, Shufei; Querfeld, Uwe; Feger, Martina; Haffner, Dieter; Hasan, Ahmed A.; Chu, Chang; Slowinski, Torsten; Bernd Dschietzig, Thomas; Schäfer, Franz; Xiong, Yingquan; Zhang, Bingbing; Rausch, Steffen; Horvathova, Katarina; Lang, Florian; Karl Krämer, Bernhard; Föller, Michael; Hocher, Berthold
• Is Part Of: FASEB journal. Volume 34:Issue 11(2020)
• Page Start: 15269
• Page End: 15281
• Publication Date: 2020-09-22
• Subjects: CKD -- FGF23 -- GFR -- non‐oxidized -- oxidized -- PTH; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202000596R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are regulators of renal phosphate excretion and vitamin D metabolism. 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‐oxPTH and oxPTH on FGF23 synthesis, however, and how n‐oxPTH and oxPTH concentrations are affected by CKD, is yet unknown. The effects of oxidized and non‐oxidized PTH 1‐34 on Fgf23 gene expression were analyzed in UMR106 osteoblast‐like cells. Furthermore, we investigated the relationship between n‐oxPTH and oxPTH, respectively, with FGF23 in two independent patients' cohorts (620 children with CKD and 600 kidney transplant recipients). While n‐oxPTH stimulated Fgf23 mRNA synthesis in vitro, oxidation of PTH in particular at Met8 led to a markedly weaker stimulation of Fgf23 . The effect was even stronger when both Met8 and Met18 were oxidized. In both clinical cohorts, n‐oxPTH—but not oxPTH—was 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‐oxPTH increased only moderately. In conclusion, n‐oxPTH, but not oxPTH, stimulates Fgf23 gene expression. The increase in PTH with decreasing GFR is mainly due to an increase in oxPTH in more advanced stages of CKD.