Effect of Cholecalciferol Supplementation on CVD, Inflammation, and Bone Metabolism Markers in CKD: A Randomized Double Blind Placebo Controlled Feasibility Trial

Background Vitamin D deficiency is common in CKD and associated with cardiovascular disease (CVD) and bone mineral metabolism. The long-term impact of cholecalciferol supplementation on CVD is unknown. We tested the effects of cholecalciferol supplementation on CVD outcomes [major adverse cardiovascular events (MACE)], progression of CKD, and markers of bone mineral metabolism and inflammation in patients with pre-dialysis CKD. Materials and Methods The study was a single-center, prospective, randomized, placebo-controlled, double blind clinical trial. Patients with CKD, between 18-75 years, estimated glomerular filtration rate 10-45 mL/min/1.73m 2 , serum 25(OH)D levels 20-50 ng/mL were enrolled. Participants received either cholecalciferol 60000 IU once/2 weeks or a matching placebo and followed up at every 3 months till 36 months after enrolment. All clinical, demographic, and biomarker characteristics were analyzed at baseline and at annual follow-up. Results 692 participants were screened, of which 126 were enrolled. However, 37 participants dropped before randomization. 89 participants were randomized: 46 to the cholecalciferol group and 43 to the placebo group. Both groups were similar with respect to MACE events, need for renal replacement therapy, and all-cause mortality. Over one year, serum 25(OH)D increased in the cholecalciferol group [Mean diff between groups: 31.89, 95% CI: 20.46 to 43.32, p <0.001]. Serum calcium increased, whereas C-reactive protein and bone-specific alkaline phosphatase levels decreased in the cholecalciferol group. Conclusions In this feasibility phase of a randomized double-blind clinical trial, Cholecalciferol treatment was safe and effective in modulating surrogate markers of inflammation and bone metabolism, but its effect on CVD outcome or progression of CKD in vitamin D-insufficient patients with stage G3-G4 CKD remains uncertain.