Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Hospital, Homburg/Saar, Germany.
Kidney Int. 2013 Jan;83(1):121-8. doi: 10.1038/ki.2012.288. Epub 2012 Aug 15.
A decreased expression of the fibroblast growth factor (FGF)-23 coreceptor Klotho was postulated as an early alteration in chronic kidney disease mineral and bone disorder, resulting in a compensatory increase in plasma FGF-23 levels. Klotho exists in both membrane-bound and secreted (sKlotho) forms, the latter of which may exert vasculoprotective effects. Here we analyzed plasma sKlotho levels in a large cohort of 312 patients with stage 2-4 chronic kidney disease, and assessed plasma levels of FGF-23, sKlotho, parathyroid hormone, and urinary fractional phosphate excretion. Patients were prospectively followed for an average of 2.2 years for the occurrence of death or initiation of renal replacement therapy. The levels of sKlotho were significantly associated with age, but not with the glomerular filtration rate or other parameters of calcium-phosphate metabolism. Moreover, while patients with high FGF-23 levels faced worst outcome even after adjustment for confounders, we found no prognostic impact of sKlotho. Thus, plasma levels of sKlotho were not related to kidney function and did not predict adverse outcome in patients with chronic kidney disease. Future studies are needed to understand how tissue expression, urinary excretion, and plasma levels of Klotho diverge in progressive chronic kidney disease.
成纤维细胞生长因子 23（FGF-23）的核心受体 Klotho 表达降低被认为是慢性肾脏病矿物质和骨异常的早期改变，导致血浆 FGF-23 水平代偿性增加。Klotho 存在于膜结合和分泌（sKlotho）形式中，后者可能发挥血管保护作用。在这里，我们分析了 312 例 2-4 期慢性肾脏病患者的大量队列中的血浆 sKlotho 水平，并评估了 FGF-23、sKlotho、甲状旁腺激素和尿磷分数排泄的血浆水平。患者前瞻性随访平均 2.2 年，以确定死亡或开始肾脏替代治疗的发生。sKlotho 的水平与年龄显著相关，但与肾小球滤过率或其他钙磷代谢参数无关。此外，尽管高 FGF-23 水平的患者即使在调整混杂因素后也面临最差的结局，但我们发现 sKlotho 没有预后影响。因此，血浆 sKlotho 水平与肾功能无关，不能预测慢性肾脏病患者的不良结局。需要进一步的研究来了解组织表达、尿排泄和血浆水平的 Klotho 在进行性慢性肾脏病中的差异。
