Yeung WG, Palmer SC, Strippoli GFM, et al. Vitamin D Therapy in Adults With CKD: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2023 Jun 24:S0272-6386(23)00693-5. doi: 10.1053/j.ajkd.2023.04.003. (Systematic review)

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.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Nephrology 6 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Interesting negative study.

Internal Medicine rater

This is an important meta-analysis demonstrating that the usefulness of vitamin D therapy in patients with CKD is questionable at best. Many nephrologists still prescribe vitamin D to all of their patients. This is more than questionable.

Nephrology rater

The most shocking finding of this systemic review and meta-analysis of vitamin D therapy in adults with CKD/ESKD is that, despite including 128 studies involving 11,270 participants, the data is so poor that the evidence remains uncertain. We still don’t know what we are doing/should be doing.
Comments from EvidenceAlerts subscribers

Dr. Anatole Besarab (8/10/2023 10:55 AM)

The problem with this metanalysis is the inability to get good data on long-term effects of vit D. Patients with CKD 3 or greater may have years before they reach ESRD or die of other causes. A trial of 3 montsh as a minimum without details on the length of the average study (and range) does not tell me what I need to know. The fact that PTH was suppressed and Alk Phos decreased indicates an effect on bone. However, no data on serum Phosphorus or Ca x P product is provided. and so the risk for vascular calcification cannot be determined.
When to start vitamin D, what form of vit D, and long-term effects are still unclear. However, at some point Nephrologists have to worry about metabolic bone disease and fracture risk since our population tends to be elderly when we get to see them.