Association of serum soluble Klotho with episode of nonfatal cardiovascular disease and mortality in maintenance hemodialysis patients

Objective To explore the association of serum soluble Klotho (sKlotho) with nonfatal cardiovascular disease (CVD) and all-cause/CVD mortality in maintenance hemodialysis (MHD) patients. Methods A total of 132 MHD patients admitted during October 2011 were enrolled. Serum sKlotho was measured by ELISA. Demographic data, including age, gender and comorbid conditions, were obtained from their medical histories, and parameters including calcium, phosphorus and albumin were assessed. The occurrence time of nonfatal CVD and all-cause mortality were recorded during the 60 months follow-up. MHD patients were categorized into four groups according to the quartiles of sKlotho: group Ⅰ (sKlotho<361.34 ng/L), group Ⅱ (361.34 ng/L≤ sKlotho<398.81 ng/L), group Ⅲ (398.81 ng/L≤sKlotho<445.99 ng/L) and group Ⅳ (sKlotho≥ 445.99 ng/L). Spearman correlation analysis and binary Logistic regression analysis were used to test the association between sKlotho and nonfatal CVD events. The impacts of sKlotho on all-cause mortality and CVD mortality were assessed by Kaplan-Meier method with log-rank test. Cox regression model was applied to evaluate the effect of sKlotho on MHD patients outcomes. Results All 132 MHD patients had sKlotho ranging from 304.02 ng/L to 550.62 ng/L. And 87 patients suffered from nonfatal CVD, with 192 episodes of nonfatal CVD during the follow-up period. The sKlotho had negative correlations with coronary artery disease (r=-0.286, P=0.001), congestive heart failure (r=-0.190, P=0.029), cerebrovascular accident (r=-0.240, P=0.006) and peripheral arterial occlusion (r=-0.243, P=0.005). The sKlotho were risk factors of coronary artery disease (OR=0.989, P=0.023) and peripheral artery occlusion (OR=0.988, P=0.046). 35 patients died in the follow-up period, including 27 death from CVD. The all-cause mortality and CVD mortality rates were significantly different among four groups (P=0.036, P=0.047). Survival rates of all-cause death and CVD death varied among four groups (χ2=8.076, P=0.044; χ2=7.866, P=0.049). Patients in group Ⅳ had higher survival rates of all-cause death and CVD death than those in group Ⅰ and group Ⅱ (all P<0.05). Multivariate Cox regression analyses revealed diabetes and age were independent risk factors for all-cause mortality and CVD mortality (all P<0.05), but sKlotho was not associated with the poor prognosis (HR=0.996, P=0.256; HR=0.996, P=0.287). Conclusions Patients with lower sKlotho have worse nonfatal CVD ratio, especially coronary artery disease and peripheral arterial occlusion. Reduced serum sKlotho is associated with all-cause and CVD mortality, but sKlotho is still not a predictive indicator of prognosis of MHD patients. Key words: Renal dialysis; Glucuronidase; Cardiovascular disease; Mortality; Soluble Klotho