Do the benefits of using calcitriol and other vitamin D receptor activators in patients with chronic kidney disease outweigh the harms?

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Chronic kidney disease (CKD) results in a cascade of changes in mineral metabolism, which produce a rise in circulating parathyroid hormone (PTH) levels and the characteristic abnormalities of secondary hyperparathyroidism (SHPT). Management of elevated PTH levels in CKD has been a therapeutic focus for over 40 years. SHPT is associated with morbidity and mortality in patients with CKD stages 3–5D, and observational studies consistently report an increased relative risk (RR) of death in dialysis patients who have PTH values at the extremes for this population (less than twice, or greater than nine times, the upper normal limit of the assay).1 Once developed, severe SHPT may be resistant to medical/pharmacological therapy, and marked parathyroid hyperplasia when associated with hypercalcaemia necessitates treatment with a parathyroidectomy.
Treatment with ‘active’ vitamin D, either calcitriol or vitamin D receptor activators (VDRA), has been the cornerstone for the prevention and management of SHPT in patients with CKD. Observational data suggest a mortality benefit with the use of VDRA in dialysis populations,3 although this has been contested by other studies.5 Furthermore, other studies suggest a benefit beyond the parathyroid‐bone axis.6 However, there are concerns raised by recent trials about the effectiveness of calcitriol/VDRA in the CKD stage 3–4 population, with potential adverse outcomes such as hypercalcaemia and elevation in fibroblast growth factor 23 (FGF23) levels.

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