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Relationship between GFR, intact PTH, oxidized PTH, non‐oxidized PTH as well as FGF23 in patients with CKD
The FASEB Journal ( IF 4.4 ) Pub Date : 2020-09-22 , DOI: 10.1096/fj.202000596r
Shufei Zeng 1, 2 , Uwe Querfeld 3 , Martina Feger 4 , Dieter Haffner 5 , Ahmed A Hasan 1, 6 , Chang Chu 1, 2 , Torsten Slowinski 2 , Thomas Bernd Dschietzig 7 , Franz Schäfer 8 , Yingquan Xiong 1, 6 , Bingbing Zhang 9, 10 , Steffen Rausch 4 , Katarina Horvathova 11 , Florian Lang 6 , Bernhard Karl Krämer 1 , Michael Föller 4 , Berthold Hocher 1, 12, 13, 14
Affiliation  

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.

中文翻译:

CKD患者GFR、完整PTH、氧化PTH、非氧化PTH以及FGF23的关系

成纤维细胞生长因子 23 (FGF23) 和甲状旁腺激素 (PTH) 是肾磷酸盐排泄和维生素 D 代谢的调节剂。在慢性肾病 (CKD) 中,循环 FGF23 和 PTH 浓度随着肾功能下降而逐渐增加。PTH 在两个甲硫氨酸残基(位置 8 和 18)处的氧化导致功能丧失。然而,n-oxPTH 和 oxPTH 对 FGF23 合成的影响,以及 n-oxPTH 和 oxPTH 浓度如何受 CKD 影响尚不清楚。在 UMR106 成骨细胞样细胞中分析了氧化和非氧化 PTH 1-34 对 Fgf23 基因表达的影响。此外,我们在两个独立的患者队列(620 名 CKD 儿童和 600 名肾移植受者)中分别研究了 n-oxPTH 和 oxPTH 与 FGF23 之间的关系。虽然 n-oxPTH 在体外刺激 Fgf23 mRNA 合成,但 PTH 的氧化尤其是在 Met8 处导致 Fgf23 的刺激明显减弱。当 Met8 和 Met18 都被氧化时,效果甚至更强。在两个临床队列中,n-oxPTH(而非 oxPTH)与 FGF23 浓度显着相关,与已知的混杂因素无关。此外,随着肾功能的逐渐恶化,完整 PTH(iPTH)和 oxPTH 显着增加,而 n-oxPTH 仅适度增加。总之,n-oxPTH 刺激 Fgf23 基因表达,而不是 oxPTH。随着 GFR 降低,PTH 增加主要是由于 CKD 晚期阶段 oxPTH 增加。当 Met8 和 Met18 都被氧化时,效果甚至更强。在两个临床队列中,n-oxPTH(而非 oxPTH)与 FGF23 浓度显着相关,与已知的混杂因素无关。此外,随着肾功能的逐渐恶化,完整 PTH(iPTH)和 oxPTH 显着增加,而 n-oxPTH 仅适度增加。总之,n-oxPTH 刺激 Fgf23 基因表达,而不是 oxPTH。随着 GFR 降低,PTH 增加主要是由于 CKD 晚期阶段 oxPTH 增加。当 Met8 和 Met18 都被氧化时,效果甚至更强。在两个临床队列中,n-oxPTH(而非 oxPTH)与 FGF23 浓度显着相关,与已知的混杂因素无关。此外,随着肾功能的逐渐恶化,完整 PTH(iPTH)和 oxPTH 显着增加,而 n-oxPTH 仅适度增加。总之,n-oxPTH 刺激 Fgf23 基因表达,而不是 oxPTH。随着 GFR 降低,PTH 增加主要是由于 CKD 晚期阶段 oxPTH 增加。总之,n-oxPTH 刺激 Fgf23 基因表达,而不是 oxPTH。随着 GFR 降低,PTH 增加主要是由于 CKD 晚期阶段 oxPTH 增加。总之,n-oxPTH 刺激 Fgf23 基因表达,而不是 oxPTH。随着 GFR 降低,PTH 增加主要是由于 CKD 晚期阶段 oxPTH 增加。
更新日期:2020-09-22
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