老年人早期肾功能损害时肾-骨轴调节因子、炎症和铁状态的改变及维生素 D 补充的影响。
Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.
机构信息
University of East Anglia, Norwich Medical School, Norwich, UK.
Freeman Hospital, Bone Clinic, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
出版信息
Age Ageing. 2024 May 1;53(5). doi: 10.1093/ageing/afae096.
CONTEXT
Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation.
OBJECTIVE AND METHODS
Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression.
RESULTS
Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR.
CONCLUSION
Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.
背景
慢性肾脏病（CKD）导致成纤维细胞生长因子 23（FGF23）和肾脏-骨骼轴发生改变。这可能部分是由炎症和铁状态的改变引起的。维生素 D 补充剂可能会减轻炎症。
目的和方法
35 名早期 CKD（估计肾小球滤过率（eGFR）为 30-60 ml/min/1.73 m2；CKDG3a/b；n=35）或正常肾功能（eGFR >90 ml/min/1.73 m2；CKDG1；n=35）的老年人接受了为期 1 年的 12000、24000 或 48000 IU D3/月的治疗。在补充前和补充后检测了肾脏-骨骼轴、炎症和铁状态的标志物。通过单变量和多变量回归确定了 c 端和完整 FGF23（cFGF23；iFGF23）的预测因子。
结果
在补充前，与 CKDG3a/b 相比，CKDG1 组的血浆 cFGF23、iFGF23、PTH、骨硬化蛋白和 TNFα明显升高，Klotho、1,25-二羟维生素 D 和铁水平降低。补充后，只有 cFGF23、25（OH）D 和 IL6 两组间有差异。补充的反应在 eGFR 组之间存在差异。仅在 CKDG1 组中，磷酸盐降低，cFGF23、iFGF23 和前胶原 I N-端肽增加。在 CKDG3a/b 组中，TNFα显著降低，铁增加。两组血浆 25（OH）D 和 IL10 增加，羧基末端胶原交联减少。在单变量模型中，cFGF23 和 iFGF23 分别由钙和磷酸盐代谢调节剂在两个时间点预测；IL6 在单变量模型中预测了 cFGF23（补充后）和 iFGF23（补充前）。铁调素在多元模型中，以 eGFR 预测了补充后的 cFGF23。
结论
在早期 CKD 中发现了肾脏-骨骼轴、炎症和铁状态调节因子的改变。维生素 D3 补充的反应在 eGFR 组之间存在差异。血浆 IL6 预测了 cFGF23 和 iFGF23，铁调素预测了 cFGF23。
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