Neyra Javier A, Hu Ming Chang
Department of Internal Medicine, University of Texas Southwestern Medical Center, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, USA; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, USA.
Bone. 2017 Jul;100:41-49. doi: 10.1016/j.bone.2017.01.017. Epub 2017 Jan 20.
The extracellular domain of transmembrane alpha-Klotho (αKlotho, hereinafter simply called Klotho) is cleaved by secretases and released into the circulation as soluble Klotho. Soluble Klotho in the circulation starts to decline early in chronic kidney disease (CKD) stage 2 and urinary Klotho possibly even earlier in CKD stage 1. Therefore soluble Klotho could serve as an early and sensitive marker of kidney function decline. Moreover, preclinical animal data support Klotho deficiency is not just merely a biomarker, but a pathogenic factor for CKD progression and extrarenal CKD complications including cardiovascular disease and disturbed mineral metabolism. Prevention of Klotho decline, re-activation of endogenous Klotho production or supplementation of exogenous Klotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiomyopathy, and alleviation of vascular calcification in CKD. Therefore Klotho is not only a diagnostic and/or prognostic marker for CKD, but the treatment of Klotho deficiency may be a promising strategy to prevent, retard, and decrease the burden of comorbidity in CKD.
跨膜α-klotho（αKlotho，以下简称Klotho）的细胞外结构域被分泌酶切割，并以可溶性Klotho的形式释放到循环中。循环中的可溶性Klotho在慢性肾脏病（CKD）2期早期就开始下降，而尿Klotho可能在CKD 1期甚至更早的时候就开始下降。因此，可溶性Klotho可作为肾功能下降的早期敏感标志物。此外，临床前动物数据表明，Klotho缺乏不仅是一种生物标志物，而且是CKD进展以及包括心血管疾病和矿物质代谢紊乱在内的肾外CKD并发症的致病因素。预防Klotho下降、重新激活内源性Klotho生成或补充外源性Klotho均与减轻肾纤维化、延缓CKD进展、改善矿物质代谢、改善心肌病以及减轻CKD中的血管钙化有关。因此，Klotho不仅是CKD的诊断和/或预后标志物，而且治疗Klotho缺乏可能是预防、延缓和减轻CKD合并症负担的一种有前景的策略。
