Yeung Wing-Chi G, Palmer Suetonia C, Strippoli Giovanni F M, Talbot Benjamin, Shah Nasir, Hawley Carmel M, Toussaint Nigel D, Badve Sunil V
Department of Nephrology, Wollongong Hospital, Sydney, Australia; George Institute for Global Health, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia.
Department of Medicine, University of Otago, Christchurch, New Zealand.
Am J Kidney Dis. 2023 Nov;82(5):543-558. doi: 10.1053/j.ajkd.2023.04.003. Epub 2023 Jun 24.
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.
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.
RCTs with≥3 months of 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 Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE.
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.
Data were limited by trials with short-term follow-up periods, 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.
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.
维生素D被广泛用于治疗慢性肾脏病-矿物质和骨异常（CKD-MBD）。我们评估了维生素D治疗对成年CKD患者死亡率、心血管、骨骼和肾脏结局的影响。
对随机对照试验（RCT）进行系统评价，通过对MEDLINE、Embase和CENTRAL进行高灵敏度检索，检索截至2023年2月25日的文献。
3、4或5期CKD成人患者，包括接受透析治疗的肾衰竭患者。肾移植受者被排除。
随访时间≥3个月、评估维生素D化合物的RCT。
由三名研究人员独立提取数据。
采用随机效应荟萃分析汇总治疗估计值。主要评价终点为全因死亡、心血管死亡和骨折。次要结局包括主要不良心血管事件、住院、骨密度、甲状旁腺切除术、进展至肾衰竭、蛋白尿、估计肾小球滤过率、高钙血症、高磷血症、CKD-MBD的生化标志物以及心血管疾病的各种中间结局指标。使用Cochrane偏倚风险（RoB）2工具评估偏倚风险。采用GRADE判定证据确定性。
总体而言，纳入了128项研究，涉及11270名参与者。与安慰剂相比，维生素D治疗可能对全因死亡无影响（相对风险[RR]，1.04；95%CI，0.84-1.24）；对骨折（RR，0.68；95%CI，0.37-1.23）和心血管死亡（RR，0.73；95%CI，0.31-1.71）的影响不确定。与安慰剂相比，维生素D治疗可降低血清甲状旁腺激素和碱性磷酸酶水平，但会升高血清钙水平。
数据受短期随访期试验、小样本量和质量欠佳的限制。
维生素D治疗并未降低CKD患者的全因死亡风险。对骨折、心血管和肾脏结局的影响不确定。
在PROSPERO注册，注册号为CRD42017057691。
慢性肾脏病（CKD）与死亡、心血管疾病和骨折风险增加相关。这种额外风险被认为与骨和矿物质代谢变化有关，导致发展为以血管钙化和骨质量降低为特征的CKD-矿物质和骨异常（CKD-MBD）。维生素D常用于治疗这种疾病。我们回顾了检验维生素D治疗对CKD影响的随机对照试验。我们发现维生素D治疗会影响血清生物标志物，包括血清钙升高。然而，它可能对CKD患者的全因死亡风险无影响，对其他临床骨骼、心血管和肾脏结局的影响也不确定。
