Abstract
Background: Soluble Klotho plays an important role in cardiovascular disease and death in chronic kidney disease (CKD). We assessed the relationship between serum soluble Klotho (sKL) level and outcome in MHD patients.Methods: Soluble Klotho was detected by ELISA. Cox regression analysis and Kaplan-Meier analysis showed the relationship between sKL and cardiovascular disease (CVD) mortality in maintenance hemodialysis (MHD) patients.Results: There were 45 cases (35.2%) of all-cause death and 36 cases (28.1%) of CVD mortality. Multivariate linear regression analysis showed that Log[iPTH] (γ = −0.224, P = 0.015) was an independent predictor of sKL level. Cox regression showed that lower sKL was associated with higher CVD mortality rate [OR = 0.401, 95% CI (0.183–0.867), P = 0.022]. Kaplan-Meier analysis showed that the CVD mortality rate increased significantly in patients with low sKL (P = 0.006). Compared with high sKL patients, low sKL patients with no or mild vascular calcification [aortic calcification score (AACs) ≤ 4] had no significant difference in all-cause mortality rate. The CVD mortality rate was significantly lower in high sKL patients (P = 0.004) than in those with low sKL. In the severe calcification group (AACs ≥ 5), all-cause and CVD mortality rates were similar between different sKL groups (P = 0.706 and 0.488, respectively). The area under the receiver-operating characteristic curve (AUC) of soluble Klotho for predicting the CVD in MHD patients with AACs ≤ 4 was 0.796 (0.647–0.946, P = 0.017), sensitivity was 0.921, and specificity was 0.50 for a cutoff value of 307.69 pg/ml.Conclusions: Lower sKL was associated with higher CVD mortality rate. Lower sKL concentration in MHD patients with no or mild calcification can predict CVD mortality.
Highlights
Cardiovascular disease (CVD) is one of the main causes of mortality in maintenance hemodialysis (MHD) patients
Multivariate linear regression analysis showed that Log[iPTH] (γ = −0.224, P = 0.015) was an independent predictor of soluble Klotho (sKL) level
Klotho gene knockout animals exhibit a wide range of vascular calcification patterns and short life expectancy [3]. sKL plays an important role in the prevention and treatment of acute kidney injury, reduces renal fibrosis induced by unilateral ureteral obstruction and slow the transition sKlotho Predict CVD in MHD
Summary
Cardiovascular disease (CVD) is one of the main causes of mortality in maintenance hemodialysis (MHD) patients. A secreted form of Klotho of 70 kDa is the product of alternative splicing, which releases the extracellular domain of membrane Klotho into blood, where it functions as a circulating substance that exerts multiple systemic biological actions on distant organs. This cleaved extracellular domain of membrane Klotho is referred to as soluble Klotho (sKL) [3]. In chronic kidney disease (CKD), sKL play an important role in cardiovascular disease and death [3,4,5]. Soluble Klotho plays an important role in cardiovascular disease and death in chronic kidney disease (CKD). We assessed the relationship between serum soluble Klotho (sKL) level and outcome in MHD patients
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