Decreased circulating α-Klotho levels predict renal outcome in patients with chronic kidney disease

Abstract

α-Klotho is mainly expressed in the renal distal tubules and functions as a cofactor for fibroblast growth factor (FGF) 23. It can be released into the circulation and exerts a pleiotropic effect. In this observational cohort study, I aimed to delineate a relationship between circulating α-Klotho levels and kidney function and to evaluate whether α-Klotho concentrations can predict renal outcome in 243 subjects, who were diagnosed chronic kidney disease (CKD) between January 2006 and December 2011. Baseline serum concentrations of α-Klotho and FGF23 were determined by enzyme-linked immunosorbant assay. Circulating α-Klotho levels gradually decreased as the stage of CKD advanced (P for trend < 0.01). In an adjusted multivariate linear regression model, log α-Klotho was independently associated with estimated glomerular filtration rates (eGFR); (β = 0.179, P < 0.001). When patients were divided into two groups according to the median value of α-Klotho, 40 patients (32.8%) with α-Klotho ≤ 396.3 pg/ml reached the composite outcome of a doubling of the baseline serum creatinine levels or end-stage renal disease compared to 17 patients (14.0%) with α-Klotho >396.3 pg/ml [hazard ratio (HR), 2.48; 95% confidential interval (CI), 1.24 to 4.95; P = 0.01]. Cox regression analysis revealed that α-Klotho independently predicted the composite renal outcome even after adjustment for age, gender, diabetes, blood pressure, eGFR, proteinuria, parathyroid hormone, and FGF23 (per 10 pg/ml increase; HR, 0.95; 95% CI, 0.93 to 0.98; P < 0.001). In conclusion, I demonstrated that circulating α-Klotho levels were decreased as kidney function declined and decreased α-Klotho concentrations significantly predicted renal outcome, suggesting that α-Klotho could be a novel biomarker for CKD progression.