背景:α-Klotho缺乏症可能会增加心血管风险并恶化生存率。我们评估了透析前慢性肾脏病(CKD)患者中α-Klotho与心血管和全因死亡率的关系。
方法:在这项前瞻性研究中,对75例非糖尿病CKD3b-4期患者进行了中位8年的随访。主要和次要结局是全因死亡率和心血管死亡率,分别。人可溶性α-KlothoELISA检测(IBL-Takara27,998-96Well),人成纤维细胞生长因子-23ELISA测定(完整FGF23,MerckMilliporeMILLENZFGF23-32K),和人硬化蛋白ELISA试剂盒(Biomedica,维也纳,BI-20492)用于测量血清α-Klotho,根据制造商的协议,在Sechenov大学认证实验室中的FGF23和硬化蛋白水平。所有患者均行超声心动图评价左心室质量指数(LVMI),辛普森法左心室射血分数,和心脏(瓣膜)钙化的半定量点评分。通过Kauppila方法进行腹部侧位X线摄影来估计腹主动脉的钙化。Cox多元回归和受试者工作特征曲线(ROC)分析用于评估死亡危险因素及其临界值。
结果:15例(20%)和9例(12%)患者达到了主要和次要终点,分别。死亡和存活患者的α-Klotho水平中位数分别为344和484pg/ml,分别(p=0.002)。在多元Cox回归模型中,基线α-Klotho水平(HR0.99,95%CI0.98-1.00,p=0.023),主动脉钙化(HR1.18,95%CI1.02-1.36,p=0.029)和左心室质量指数(LVMI)(HR1.04,95%CI1.00-1.08,p=0.033)与主要终点相关,而α-Klotho(HR0.99,95%CI0.98-1.00,p=0.029),主动脉钙化(HR1.23,95%CI1.07-1.42,p=0.003)和LVMI(HR1.04,95%CI1.00-1.08,p=0.021)与次要终点相关.通过ROC分析,α-Klotho水平曲线下面积(AUC)最高,也就是说,主要终点为0.766(95%CI0.70-0.82),次要终点为0.842(95%CI0.79-0.90),临界值为412pg/ml(HR3.06,95%CI1.36-6.89,p=0.007)和368pg/ml(HR4.84,95%CI1.59-14.73,p=0.005),分别。
结论:在透析前CKD患者中,α-Klotho水平与全因死亡率和心血管死亡率相关,可能被认为是早期预后指标。
BACKGROUND: α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients.
METHODS: In this prospective study, 75 non-diabetic CKD stage 3b-4 patients were followed-up for a median of 8 years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32 K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers\' protocols. All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcification of the abdominal aorta. Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values.
RESULTS: Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484 pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC) by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412 pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368 pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively.
CONCLUSIONS: In pre-dialysis CKD patients, α-Klotho levels are associated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.