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

Background: Vitamin D deficiency is common in chronic kidney disease (CKD) and associated with cardiovascular disease (CVD) and bone mineral metabolism. Despite short term favourable effects, long term impact of cholecalciferol supplementation is unknown. We tested the effects of cholecalciferol supplementation on CVD outcome [major adverse cardiovascular events (MACE)], progression of CKD and markers of bone-mineral metabolism and inflammation in patients with pre-dialysis CKD. Methods: The study was a single centre, prospective, randomized (1:1), placebo controlled, double blind clinical trial. Inclusion criteria were ages between 18-75 years, estimated glomerular filtration rate 10-45 ml/min/1.73m2, serum 25(OH)D levels 20-50 ng/ml and clinically stable course for last 3 months. After 2 weeks run-in phase, participants received either cholecalciferol 60000 IU once/2 weeks or matching placebo and followed up at every 3 months till 36 months after enrolment. All clinical, demographic characters and biomarkers were analysed at baseline and annual follow up. Results: 692 participants were screened, out of which 126 were enrolled. However, 37 participants dropped out before randomization on account of COVID-19 related lockdowns or other reasons. The pilot phase was stopped in April 2023. Follow up course of 89 participants were available till that time: 46 participants were in the cholecalciferol group whereas 43 were in the placebo group. Both the groups were similar with respect to MACE events, need of 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: Cholecalciferol treatment did not affect CVD outcome or progression of CKD in vitamin D insufficient patients with stage G3-G4 CKD, however it favourably affected markers of inflammation and bone metabolism in these patients. Trial Registration: The trial was prospectively registered at the Clinical Trials Registry of India (www.ctri.nic.in, trial registration number CTRI/2019/05/019211 dated 20 May 2019).