Effectiveness and safety of vitamin D compounds in people with chronic kidney disease: A systematic review and meta-analysis

Vitamin D therapy is commonly prescribed for people with chronic kidney disease to improve biochemical perturbations; however, evidence of effects on patient-centred outcomes such as mortality, cardiovascular events and fracture are uncertain. We updated a systematic review and meta-analysis of all available randomised controlled trials on vitamin D compounds in chronic kidney disease to determine its effects on clinical and biochemical outcomes as well as its optimum route of administration, frequency and dose. Searches of MEDLINE, EMBASE and Cochrane Renal Group specialised register databases identified 164 eligible studies that enrolled 10,333 participants. Based on low to very low quality evidence assessed using GRADE methodology, vitamin D had uncertain effects on all-cause mortality, fracture, parathyroidectomy, bone pain and progression to end-stage kidney disease. Compared to placebo, new vitamin D compounds may reduce major cardiovascular events by 18 to 58 people per 1000 people who have chronic kidney disease not receiving dialysis. Vitamin D reduced serum parathyroid hormone levels by 116 pg/ml (12.7 pmol/l) on average, while increasing serum calcium by 0.33 mg/dl (0.08 mmol/l) and phosphorus by 0.19 mg/dl (0.06 mmol/l) when compared to placebo. We are moderately confident that vitamin D therapy increases episodes of hypercalcaemia by 14 to 64 people per 1000 people treated. Effects of different vitamin D compounds, routes of administration, frequency and doses of vitamin D were not discernible from existing evidence. Additional trials are likely to change these estimated treatment effects and are needed to increase confidence in the evidence that informs clinical practice guidelines for vitamin D in people with chronic kidney disease