Optimal vitamin D, calcitriol, and vitamin D analog replacement in chronic kidney disease: to D or not to D: that is the question.

PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) are often insufficient in 25(OH) vitamin D and are almost uniformly deficient in 1,25(OH)2 vitamin D, because of decreased renal hydroxylation resulting from hyperphosphatemia and elevated fibroblast growth factor-23 (FGF-23) levels. These same abnormalities lead to secondary hyperparathyroidism for which the administration of calcitriol or vitamin D analogs has been the mainstay of therapy for decades. This review summarizes new trials of vitamin D, calcitriol, and its analogs over the last 2 years.

RECENT FINDINGS: In addition to the endocrine effects of the vitamin D axis on bone and mineral metabolism, studies have demonstrated there is also extrarenal conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D in multiple cells leading to autocrine effects. This advance has led to the speculation that CKD patients may also need to be supplemented with ergocalciferol or cholecalciferol. Unfortunately, to date, the majority of interventional studies have focused on biochemical end points. There are no randomized controlled trials demonstrating that therapy with any formulation of vitamin D results in improved patient level outcomes.

SUMMARY: Despite the physiologic importance of vitamin D in health and disease, more research is required to determine which vitamin D derivative is required for optimal health in CKD patients.