Department of Nephrology, Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Department of Nephrology, Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China,
Cardiorenal Med. 2020;10(3):175-187. doi: 10.1159/000506380. Epub 2020 Apr 15.
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.
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.
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).
These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.
实验研究表明，Klotho 缺乏是 CKD 相关并发症的致病因素，包括心血管疾病（CVD）。然而，血清 Klotho 与非糖尿病 CKD 患者临床结局之间的关系仍需进一步阐明。我们旨在确定血清 Klotho 水平是否与无糖尿病的透析前 CKD 患者的 CVD 事件和死亡率相关。
共纳入 336 例无糖尿病的 CKD 2-5 期透析前患者，自 2014 年底至 2019 年 1 月进行 CVD 事件和全因死亡率随访。采用 ELISA 法检测血清 Klotho，并根据血清 Klotho 类别分为四分之一（最低、中间、第二高和最高四分位数）。
中位随访 3.52 年后（IQR 3.34-3.76），Kaplan-Meier 分析显示，与 Klotho 水平处于最高四分位数（参考类别）的参与者相比，Klotho 水平处于最低四分位数的患者全因死亡率风险更高（HR = 7.05；95%CI 1.59-31.25），CVD 事件风险更高（HR = 3.02；95%CI 1.45-6.30）。此外，中间 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，在多变量调整模型中，最低 Klotho 四分位数与全因死亡率仍显著相关（HR = 5.17；95%CI 1.07-24.96），中间 Klotho 四分位数与 CVD 事件风险仍显著相关（HR = 2.32；95%CI 1.03-5.21）。
这些结果表明，血清 Klotho 水平较低与非糖尿病透析前 CKD 患者的全因死亡率和 CVD 事件独立相关。
