Drew David A, Katz Ronit, Kritchevsky Stephen, Ix Joachim, Shlipak Michael, Gutiérrez Orlando M, Newman Anne, Hoofnagle Andy, Fried Linda, Semba Richard D, Sarnak Mark
Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, Massachusetts;
Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
J Am Soc Nephrol. 2017 Jun;28(6):1859-1866. doi: 10.1681/ASN.2016080828. Epub 2017 Jan 19.
CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble -klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism.
慢性肾脏病似乎是一种可溶性α-klotho蛋白缺乏的病症。尽管已知低水平的可溶性α-klotho蛋白与促进肾损伤的病症（如氧化应激和纤维化）之间存在关联，但关于可溶性α-klotho蛋白水平与肾功能变化之间的纵向关联的信息却很少。我们在健康老龄化与身体成分研究（一项针对老年人的队列研究）中的2496名参与者中检测了血清可溶性α-klotho蛋白。评估了可溶性α-klotho蛋白水平与肾功能下降（相对下降：估算肾小球滤过率下降≥30%；绝对下降：估算肾小球滤过率每年下降>3 ml/min）以及新发慢性肾脏病（新发估算肾小球滤过率<60 ml/min/1.73 m²且每年下降>1 ml/min）之间的关联。我们对模型进行了人口统计学、基线估算肾小球滤过率、尿白蛋白与肌酐比值、合并症以及矿物质代谢指标的校正。参与者的平均（标准差）年龄为75（3）岁，52%为女性，38%为黑人。α-klotho蛋白水平的中位数（第25、75百分位数）为630（477，817）pg/ml。在完全校正的模型中，α-klotho蛋白水平每升高两倍，与肾功能下降几率降低相关（估算肾小球滤过率下降30%时的比值比为0.78 [95%置信区间，0.66至0.93]，估算肾小球滤过率每年下降>3 ml/min时的比值比为0.85 [95%置信区间，0.73至0.98]），但与新发慢性肾脏病无关（发病率比为0.90 [95%置信区间，0.78至1.04]）。总体而言，较高的可溶性α-klotho蛋白水平与较低的肾功能下降风险独立相关。未来的研究应尝试在其他队列中重复这些结果并评估潜在机制。
