Cholecalciferol supplementation reduces soluble Klotho concentration in hemodialysis patients

Abstract

Low levels of vitamin D are linked to numerous adverse clinical conditions in hemodialysis (HD) patients, including disturbances of mineral and bone metabolism and increased mortality. Klotho, a molecule involved in such processes as phosphate homeostasis and aging, exists in 2 forms: a transmembrane protein acting as a coreceptor for fibroblast growth factor 23 (FGF-23) and soluble form, which is formed by cleavage of the extracellular domain of this molecule. The aim of the study was to evaluate the effect of cholecalciferol supplementation on soluble Klotho levels in HD patients. This was a prospective, open-label trial examining the effects of cholecalciferol supplementation on selected laboratory markers in 22 patients on HD. Vitamin D deficiency was assessed by the measurement of 25-hydroxyvitamin D [25(OH)D] levels. Soluble Klotho, intact FGF-23, intact parathormone (iPTH), and markers of bone formation and resorption were measured at baseline and after 12 weeks of cholecalciferol supplementation. The levels of 25(OH)D increased, while those of iPTH and cross-linked C-telopeptide of type 1 collagen decreased significantly. Cholecalciferol treatment reduced the median concentration of soluble Klotho (from 438.73 pg/ml; interquartile range, 257.99-865.51 pg/ml; to 370.94 pg/ml; 181.72-710.91 pg/ml; P <0.05). FGF‑23 levels were not affected by the treatment. Supplementation with cholecalciferol in HD patients decreases soluble Klotho levels without affecting the FGF-23 concentration. Replenishment of vitamin D stores results in a decrease in iPTH levels and reduced bone resorption.