ABSTRACT
OBJECTIVE: Vitamin D-fibroblast growth factor-23 (FGF-23)-klotho forms an axis that takes part at least in cardiovascular complications in patients with chronic kidney disease. This study aimed to assess the effects of cholecalciferol supplementation on FGF23 and α-klotho in patients with hypovitaminosis D requiring hemodialysis. METHODS: In a single-center, parallel-arm, randomized, double-blind, placebo-controlled trial, 86 patients with hypovitaminosis D requiring hemodialysis were enrolled. The patients were randomized into 2 groups (n = 43 each) to receive either 50,000 IU of cholecalciferol or placebo every week for 12 weeks. Accordingly, the serum levels of FGF23 and klotho were measured by ELISA and compared between both groups. RESULTS: Serum 25OH(D) levels increased in participants who received cholecalciferol supplementation compared with participants who received placebo (P = .006). In addition, serum FGF23 decreased and α-klotho levels increased in the supplemented group compared with placebo. However, the before-after differences between cholecalciferol supplement and placebo were significant only for α-klotho (P = .035). These effects were not accompanied by changes in the levels of phosphate, total and ionized calcium, and intact parathyroid hormone. CONCLUSION: Cholecalciferol supplementation of 50,000 IU for 12 weeks increases α-klotho levels in the serum of kidney failure patients undergoing hemodialysis. This may suggest that patients receiving maintenance hemodialysis can benefit from using cholecalciferol supplementation and increase in serum α-klotho levels.
Subject(s)
Cholecalciferol , Vitamin D Deficiency , Dietary Supplements , Double-Blind Method , Female , Fibroblast Growth Factors , Humans , Male , Renal Dialysis/adverse effects , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapyABSTRACT
The impacts of glucocorticoids (GCs) are mainly mediated by a nuclear receptor (GR) existing in almost every tissue. The GR regulates a wide range of physiological functions, including inflammation, cell metabolism, and differentiation playing a major role in cellular responses to GCs and stress. Therefore, the dysregulation or disruption of GR can cause deficiencies in the adaptation to stress and the preservation of homeostasis. The number of GR polymorphisms associated with different diseases has been mounting per year. Tackling these clinical complications obliges a comprehensive understanding of the molecular network action of GCs at the level of the GR structure and its signaling pathways. Beyond genetic variation in the GR gene, epigenetic changes can enhance our understanding of causal factors involved in the development of diseases and identifying biomarkers. In this review, we highlight the relationships of GC receptor gene polymorphisms and epigenetics with different diseases.
