Background: Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes. Methods: A total of 336 CKD stage 2–5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category. Results: After a median follow-up of 3.52 years (IQR 3.34–3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59–31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45–6.30). In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21–5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07–24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03–5.21). Conclusion: These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.
Cardiorenal Med 2020;10:175–187

中文翻译：

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非糖尿病慢性肾脏疾病的血清Klotho，心血管事件和死亡率。

背景：实验研究表明，Klotho缺乏症是CKD相关并发症（包括心血管疾病（CVD））的致病因素。然而，非糖尿病CKD患者的血清Klotho与临床结局之间的关联需要进一步阐明。我们旨在确定无糖尿病的透析前CKD患者的血清Klotho水平是否与CVD事件和死亡率相关。方法：从2014年底至2019年1月，共招募336名无糖尿病的CKD 2-5期透析前无糖尿病患者，并随访其CVD事件和总死亡率。通过ELISA检测血清Klotho，并根据其血清Klotho类别将其分为四分位数（最低，中，第二高和最高四分位数）。结果：经过3.52年的中位随访（IQR 3.34–3.76），Kaplan-Meier分析显示，与最高四分位数（参考类别）的Klotho水平的参与者相比，最低Klotho四分位数的参与者与更高的全因死亡率风险（HR = 7.05； 95％CI 1.59-31.25）和更高的CVD事件风险（HR = 3.02； 95％CI 1.45-6.30）。此外，中间的Klotho四分位数也与CVD事件风险相关（HR = 2.56； 95％CI 1.21-5.41）。此外，在多元调整模型中，最低的Klotho四分位数仍与全因死亡率显着相关（HR = 5.17； 95％CI 1.07–24.96），而中间的Klotho四分位数与CVD事件风险保持显着相关性（HR = 2.32； 95％CI 1.03–5.21）。结论：这些结果表明，较低的血清Klotho水平与非糖尿病前透析CKD患者的总死亡率和CVD事件独立相关。
2020年《心血管内科》; 10：175–187