Extended-release calcifediol in stage 3-4 chronic kidney disease: a new therapy for the treatment of secondary hyperparathyroidism associated with hypovitaminosis D
Mario Cozzolino, Paola Minghetti, Pierluigi Navarra, Mario Cozzolino, Paola Minghetti, Pierluigi Navarra
Abstract
A high percentage of patients with chronic kidney disease have hypovitaminosis D, which is a driver of secondary hyperparathyroidism and an important factor in chronic kidney disease-mineral and bone disorder. Vitamin D deficiency (serum total 25-OH vitamin D levels < 30 ng/mL) occurs early in the course of chronic kidney disease and treatment guidelines recommend early intervention to restore 25-OH vitamin D levels as a first step to prevent/delay the onset/progression of secondary hyperparathyroidism. The vitamin D forms administered to replace 25-OH vitamin D include cholecalciferol, ergocalciferol, and immediate- or extended-release formulations of calcifediol. Most patients with intermediate-stage chronic kidney disease will develop secondary hyperparathyroidism before dialysis is required. Control of parathyroid hormone levels becomes a major focus of therapy in these patients. This article focuses on the position of extended-release calcifediol in the treatment of patients with stage 3-4 chronic kidney disease and secondary hyperparathyroidism with hypovitaminosis D. Several characteristics of extended-release calcifediol support its use in the intermediate stages of chronic kidney disease. The pharmacokinetics of extended-release calcifediol make it effective for replenishing 25-OH vitamin D levels, with minimal impact on vitamin D catabolism from fibroblast-growth factor-23 and CYP24A1 upregulation. Extended-release calcifediol increases circulating 25-OH vitamin D levels in a dose-dependent manner and lowers parathyroid hormone levels by a clinically relevant extent, comparable to what can be achieved by administering active vitamin D analogues, though with a lower risk of hypercalcaemia and hyperphosphataemia. Active vitamin D analogues are reserved for patients undergoing dialysis or pre-dialysis patients with severe progressive secondary hyperparathyroidism.
Keywords: Calcifediol; Chronic kidney disease; Parathyroid hormone; Secondary hyperparathyroidism; Vitamin D; Vitamin D insufficiency.
Conflict of interest statement
MC declares advisory/lecture fees from Amgen, Abbvie, Shire, Vifor-Pharma, and Baxter. PM declares no competing interest. PN has attended a board meeting supported by Vifor Pharma.
© 2021. The Author(s).
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Source: PubMed