Vitamin D Therapy in Adults With CKD: A Systematic Review and Meta-analysis

Abstract

Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We aimed to evaluate the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD. Systematic review of randomized controlled trials (RCT) with highly-sensitive searching of MEDLINE, Embase, and CENTRAL, through 25 February 2023. Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded. RCTs with ≥3 months follow-up evaluating a vitamin D compound. Data were extracted independently by three investigators. Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane RoB 2 tool. Evidence certainty was adjudicated using GRADE. Overall, 128 studies involving 11,270 participants were included. Compared to placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR] 1.04; 95% CI 0.84 to 1.24); and uncertain effects on fracture (RR 0.68; 95% CI 0.37 to 1.23) and cardiovascular death (RR 0.73; 95% CI 0.31 to 1.71). Compared to placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium. Data were limited by trials with short-term follow-up, small sample size, and the suboptimal quality. Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture, and cardiovascular, and kidney outcomes were uncertain.