Objective: To review the data supporting combination therapy with vitamin D and vitamin D receptor activators (VDRAs) in patients with stage 5 chronic kidney disease (CKD).
Data sources: Literature was searched using PubMed and EMBASE using the terms kidney disease, kidney failure-chronic, and vitamin D. Limits applied included humans, adults (19 years or older), and clinical trials (and related), with publication dates between January 1, 1980, and May 16, 2011.
Study selection and data extraction: All English-language publications were analyzed for relevance. Studies appropriate to the objective were evaluated, including 3 prospective observational studies, 1 prospective cohort study, and 1 retrospective study.
Data synthesis: To our knowledge, there have been no randomized controlled trials evaluating the safety and efficacy of vitamin D supplementation in combination with VDRA therapy in patients with stage 5 CKD. Relatively small observational studies have demonstrated improvements in 25-hydroxyvitamin D (25-OHD) concentrations and markers of mineral and bone metabolism as well as reduced VDRA use in patients with stage 5 CKD. Not all patients in these studies were receiving VDRA therapy. Therapy was safe, with no patients exceeding the recommended upper limit for 25-OHD concentrations and only a small percentage experiencing transient/correctable hypercalcemia.
Conclusions: Vitamin D supplementation to maintain 25-OHD concentrations at 20-30 ng/mL or higher with or without VDRA therapy is inexpensive, appears safe, and may have additional health benefits in patients with stage 5 CKD. Well-designed, randomized controlled trials are needed to determine the efficacy and safety of combination vitamin D therapy in patients with stage 5 CKD.