TY - JOUR
T1 - Soluble α-klotho and its relation to kidney function and fibroblast growth factor-23
AU - Scholze, Alexandra
AU - Liu, Ying
AU - Pedersen, Lise
AU - Xia, Shengqiang
AU - Roth, Heinz J
AU - Hocher, Berthold
AU - Rasmussen, Lars Melholt
AU - Tepel, Martin
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Age Factors
KW - Aged
KW - Alkaline Phosphatase/blood
KW - Female
KW - Fibroblast Growth Factors/blood
KW - Glomerular Filtration Rate/physiology
KW - Glucuronidase/blood
KW - Humans
KW - Kidney/physiopathology
KW - Male
KW - Middle Aged
KW - Renal Insufficiency, Chronic/blood
KW - Vitamin D/analogs & derivatives
U2 - 10.1210/jc.2013-4171
DO - 10.1210/jc.2013-4171
M3 - Article
C2 - 24606097
VL - 99
SP - E855-61
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -