Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohashu, Oko-cho, Nankoku 783-8505, Japan.
Clin Exp Nephrol. 2012 Oct;16(5):722-9. doi: 10.1007/s10157-012-0621-7. Epub 2012 Mar 29.
α-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble α-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble α-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble α-Klotho levels in human CKD.
A total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured.
Serum soluble α-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (P < 0.0001) and inversely with serum creatinine level (P < 0.01). Interestingly, α-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1 (P = 0.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble α-Klotho was associated inversely with log-transformed FGF23 level (P < 0.01).
Our data indicate that soluble α-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble α-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.
α-klotho 最初被鉴定为衰老基因，后来被证明是调节磷酸盐代谢的调节剂。成纤维细胞生长因子 23（FGF23）是磷酸盐代谢的关键调节剂。慢性肾脏病（CKD）患者血清可溶性α-klotho 水平以前尚未确定，尤其是与 FGF23 和肌酐水平的关系。本研究旨在探讨 CKD 患者肾功能、年龄和 FGF23 水平是否调节血清可溶性α-klotho 水平。这是首次报道测量人类 CKD 中可溶性α-klotho 水平的效用。
共纳入 292 例 CKD 患者。采集血清样本，采用酶联免疫吸附试验试剂盒测定 FGF23 和可溶性α-klotho 水平。此外，还测定了血清肌酐、血红蛋白、白蛋白、钙和磷水平。
血清可溶性α-klotho 水平与估计肾小球滤过率（eGFR）呈正相关（P<0.0001），与血清肌酐水平呈负相关（P<0.01）。有趣的是，与 CKD 1 期相比，2 期 CKD 患者的α-klotho 水平显著降低（P=0.0001）。血清 FGF23 水平与血清肌酐呈正相关，与 eGFR 呈负相关。与 CKD 1 期相比，5 期 FGF23 水平显著升高。可溶性α-klotho 与 log 转换的 FGF23 水平呈负相关（P<0.01）。
我们的数据表明，与 CKD 1 期相比，2 期 CKD 患者的可溶性α-klotho 水平显著降低，而不仅仅是在疾病的晚期。因此，可溶性α-klotho 可能是 CKD 诊断的一个新的生物标志物，特别是在早期。
