Tan Sven-Jean, Smith Edward R, Holt Stephen G, Hewitson Tim D, Toussaint Nigel D
Department of Nephrology, Royal Melbourne Hospital, Parkville, Australia.
Department of Medicine (RMH), University of Melbourne, Melbourne, Australia.
Clin Kidney J. 2017 Jun;10(3):397-404. doi: 10.1093/ckj/sfw146. Epub 2017 Feb 28.
Membrane-bound α-klotho functions as a co-receptor with fibroblast growth factor receptor at the renal tubule conferring specificity to fibroblast growth factor-23 (FGF-23), allowing it to inhibit tubular phosphate reabsorption at physiological concentrations. α-klotho also exists as a soluble protein. However, the complex interrelationships between soluble α-klotho (sKl), FGF-23 and phosphate reabsorption are poorly understood, with little known about the links between sKl, FGF-23 and phosphate reabsorption in chronic kidney disease (CKD). This study addresses this issue in a cohort of patients with and without CKD. We conducted a single-centre, cross-sectional study of contemporaneously obtained samples of blood and 24-h urine biochemistry along with sKl and intact FGF-23 (iFGF-23) from non-dialysis-dependent CKD patients and healthy volunteers. Pearson's correlation coefficients were used to determine correlations between natural log-transformed (Ln) sKl and iFGF-23 with other parameters of interest. Backward multivariate analysis was undertaken to evaluate the relationship between mineral parameters. One hundred and sixteen participants (77 with CKD and 39 healthy volunteers) were studied, of which 74 (63.8%) were male. The median age was 61 (interquartile range 49-71) years. Those with CKD had lower sKl (408 versus 542 pg/mL), higher iFGF-23 (94 versus 41 pg/mL), higher fractional excretion of phosphate (25.05 versus 10.98%) and lower daily urinary phosphate excretion (UPE) (24.8 versus 32.3 mmol/L) compared with healthy volunteers (all P 0.002). Age correlated inversely and estimated glomerular filtration rate (eGFR) correlated positively with phosphate reabsorption and Ln(sKl), while the opposite was seen with Ln(iFGF23). Upon multivariate analysis, eGFR, Ln(sKl) and parathyroid hormone were independently associated with phosphate reabsorption, whereas Ln(iFGF-23) was not, after adjustment for age. Abnormalities in phosphate regulatory pathways are disturbed early in CKD. While iFGF-23 is associated with phosphate excretion on univariate analyses, sKl demonstrates a significant association with phosphate reabsorption independent of iFGF-23, and this relationship deserves further exploration.
膜结合型α-klotho作为一种共受体，与肾小管中的成纤维细胞生长因子受体共同作用，赋予成纤维细胞生长因子23（FGF-23）特异性，使其能够在生理浓度下抑制肾小管对磷酸盐的重吸收。α-klotho也以可溶性蛋白的形式存在。然而，可溶性α-klotho（sKl）、FGF-23与磷酸盐重吸收之间复杂的相互关系目前仍知之甚少，对于慢性肾脏病（CKD）中sKl、FGF-23与磷酸盐重吸收之间的联系更是了解甚少。本研究在一组患有和未患有CKD的患者中探讨了这一问题。我们对非透析依赖型CKD患者和健康志愿者同时采集的血液样本、24小时尿液生化指标以及sKl和完整FGF-23（iFGF-23）进行了单中心横断面研究。使用Pearson相关系数来确定自然对数转换后的（Ln）sKl和iFGF-23与其他感兴趣参数之间的相关性。进行向后多变量分析以评估矿物质参数之间的关系。共研究了116名参与者（77名CKD患者和39名健康志愿者），其中74名（63.8%）为男性。年龄中位数为61岁（四分位间距49 - 71岁）。与健康志愿者相比，CKD患者sKl较低（408对542 pg/mL）、iFGF-23较高（94对41 pg/mL）、磷酸盐排泄分数较高（25.05对10.98%）且每日尿磷酸盐排泄量（UPE）较低（24.8对32.3 mmol/L）（所有P < 0.
