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  • Title: Soluble α-klotho and its relation to kidney function and fibroblast growth factor-23.
    Author: Scholze A, Liu Y, Pedersen L, Xia S, Roth HJ, Hocher B, Rasmussen LM, Tepel M.
    Journal: J Clin Endocrinol Metab; 2014 May; 99(5):E855-61. PubMed ID: 24606097.
    Abstract:
    CONTEXT: Relations between fibroblast growth factor-23 (FGF-23), soluble α-klotho (s-α-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α-klotho requires further study. OBJECTIVES: Our objectives were to analyze the relation of s-α-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-α-klotho to cholecalciferol. PATIENTS, DESIGN, AND SETTING: Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D and chronic renal insufficiency). INTERVENTIONS: Interventions included 40 000 IU cholecalciferol or placebo weekly. MAIN OUTCOME MEASURE: S-α-klotho was determined by ELISA with antihuman klotho antibodies 67G3 and 91F1. RESULTS: For all patients, s-α-klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations, a positive association of s-α-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-α-klotho below 204 pg/mL showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase compared with patients with higher s-α-klotho. Treatment with cholecalciferol significantly increased 1,25-dihydroxyvitamin D. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-α-klotho. CONCLUSIONS: CKD patients with s-α-klotho below 204 pg/mL had higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase. An association of s-α-klotho with eGFR was observed only in the presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-α-klotho concentrations.
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