The survival advantage for haemodialysis patients taking vitamin D is questioned: findings from the Dialysis Outcomes and Practice Patterns Study
The survival advantage for haemodialysis patients taking vitamin D is questioned: findings from the Dialysis Outcomes and Practice Patterns Study
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DOI：
10.1093/ndt/gfn592
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发表时间：
2009-03-01
影响因子：
6.1
通讯作者：
Port, Friedrich K.
中科院分区：
文献类型：
--
作者：
Tentori, Francesca;Albert, Justin M.;Port, Friedrich K.
背景。美国大型透析机构对血液透析患者的回顾性研究表明，静脉注射维生素D可能与生存益处有关。然而，服用维生素D处方的患者通常比没有服用的患者更健康，这表明根据适应症进行治疗可能会对先前的发现产生偏见。此外，在最近的CKD患者荟萃分析中，没有显示维生素D相关的生存益处。由于在标准回归或边际结构模型（MSMs）中不能完全解释由测量和未测量混杂因素引起的适应症治疗偏倚，因此本研究使用标准回归和MSMs与扩展的协变量集评估了透析结果和实践模式研究（DOPPS）参与者中维生素D与死亡率之间的关系。以及通过工具变量模型来减少由于未测量混杂因素造成的潜在偏差。该研究分析了1996年至2007年间来自12个国家的38066名DOPPS参与者的数据。使用标准基线和时变Cox回归模型评估死亡风险，并根据人口统计学和详细的合并症以及mms进行调整。在类似于工具变量分析的模型中，处方维生素D的患者的设施百分比，根据患者病例组合进行调整，用于预测患者水平的死亡率。与其他国家相比，美国的维生素D处方明显更高。平均而言，服用维生素D的患者比没有服用的患者有更少的合并症。在调整的时变标准回归模型中，维生素D治疗与较低的死亡率相关[相对比(RR) = 0.92(95%可信区间：0.87-0.96)]，基线MSMs [RR = 0.84(0.78-0.98)]和时变MSMs [RR = 0.78(0.73-0.84)]。在调整后的基线标准回归模型中，有或没有维生素D处方的患者的死亡率没有显著差异[RR = 0.98(0.93-1.02)]，或在维生素D处方更频繁的医疗机构执业的患者[维生素D处方第75百分位对第25百分位的医疗机构的RR = 0.99(0.94-1.04)]。由于未测量的混杂因素，在容易产生偏差的模型中，维生素D与生存益处相关。与随机对照研究的荟萃分析一致，在工具变量模型中没有观察到死亡率的差异，这些模型往往更独立于未测量的混杂因素。这些发现表明，需要对血液透析患者的维生素D和临床结果进行随机对照试验，并且可以在伦理上进行。
Background. Retrospective studies of haemodialysis patients from large dialysis organizations in the United States have indicated that intravenous vitamin D may be associated with a survival benefit. However, patients prescribed vitamin D are generally healthier than those who are not, suggesting that treatment by indication may have biased previous findings. Additionally, no survival benefit associated with vitamin D has been shown in a recent meta-analysis in CKD patients. Because treatment-by-indication bias due to both measured and unmeasured confounders cannot be completely accounted for in standard regression or marginal structural models (MSMs), this study evaluates the association between vitamin D and mortality among participants in the Dialysis Outcomes and Practice Patterns Study (DOPPS) using standard regression and MSMs with an expanded set of covariates, as well as by instrumental variable models to minimize potential bias due to unmeasured confounders.Methods. Data from 38 066 DOPPS participants from 12 countries between 1996 and 2007 were analysed. Mortality risk was assessed using standard baseline and time-varying Cox regression models, adjusted for demographics and detailed comorbidities, and MSMs. In models similar to instrumental variable analysis, the facility percentage of patients prescribed vitamin D, adjusted for the patient case mix, was used to predict patient-level mortality.Results. Vitamin D prescription was significantly higher in the USA compared to other countries. On average, patients prescribed vitamin D had fewer comorbidities compared to those who were not. Vitamin D therapy was associated with lower mortality in adjusted time-varying standard regression models [relative ratio (RR) = 0.92 (95% confidence interval: 0.87-0.96)] and baseline MSMs [RR = 0.84 (0.78-0.98)] and time-varying MSMs [RR = 0.78 (0.73-0.84)]. No significant differences in mortality were observed in adjusted baseline standard regression models for patients with or without vitamin D prescription [RR = 0.98 (0.93-1.02)] or for patients in facility practices where vitamin D prescription was more frequent [RR for facilities in 75th versus 25th percentile of vitamin D prescription = 0.99 (0.94-1.04)].Conclusions. Vitamin D was associated with a survival benefit in models prone to bias due to unmeasured confounding. In agreement with a meta-analysis of randomized controlled studies, no difference in mortality was observed in instrumental variable models that tend to be more independent of unmeasured confounding. These findings indicate that a randomized controlled trial of vitamin D and clinical outcomes in haemodialysis patients are needed and can be ethically conducted.