Soluble α-klotho and its relation to kidney function and fibroblast growth factor-23

Alexandra Scholze, Ying Liu, Lise Pedersen, Shengqiang Xia, Heinz J Roth, Berthold Hocher, Lars Melholt Rasmussen, Martin Tepel

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind99
Udgave nummer5
Sider (fra-til)E855-E861
ISSN0021-972X
DOI
StatusUdgivet - 1. maj 2014

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