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

Abstract

Rationale & objective: Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD.

Study design: Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023.

Setting & study populations: Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded.

Selection criteria for studies: RCTs with≥3 months of follow-up evaluating a vitamin D compound.

Data extraction: Data were extracted independently by three investigators.

Analytical approach: 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 Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.

Results: Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium.

Limitations: Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality.

Conclusions: 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.

Trial registration: Registered at PROSPERO with study number CRD42017057691.

Plain-language summary: Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.

Keywords: Bone mineral density; chronic kidney disease; chronic kidney disease–mineral and bone disorder; kidney failure; meta-analysis; secondary hyperparathyroidism; vitamin D.