Associations among RAAS Inhibitors, Residual Kidney Function, and CV Events in PD

PD 中 RAAS 抑制剂、残余肾功能和 CV 事件之间的关联

基本信息

批准号：
8393127
负责人：
Jenny I Shen
金额：
$ 5.94万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8393127
关键词：
Age American Angiotensin II Receptor Angiotensin-Converting Enzyme Inhibitors Anuria Biological Preservation Blood Pressure Cardiac Cardiovascular Diseases Cardiovascular system Cause of Death Characteristics Chronic Kidney Failure Clinical Computerized Medical Record Creatinine Data Data Analyses Data Set Data Sources Databases Diabetes Mellitus Diabetic Nephropathy Dialysis patients Dialysis procedure Effectiveness End stage renal failure Epidemiologic Methods Ethnic Origin Event Health Heart failure Hemodialysis Hospitalization Hour Hypertension Information Systems Kidney Laboratories Lead Life Light Measurement Measures Methods Modeling Myocardial Infarction Observational Study Outcome Patients Pattern Peritoneal Dialysis Peritonitis Pharmaceutical Preparations Provider Race Recording of previous events Renal function Research Residual state Risk Services Statistical Methods Structural Models Subgroup Techniques Testing Time Training Update Urea Work adverse outcome base cardiovascular risk factor cohort comparative effectiveness compare effectiveness design effectiveness research experience improved inhibitor/antagonist interest mortality sex time use treatment as usual

项目摘要

DESCRIPTION (provided by applicant): In patients with chronic kidney disease not on dialysis, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) slow the progression of diabetic nephropathy and reduce cardiovascular (CV) risk. However, data on their effectiveness in patients undergoing peritoneal dialysis (PD) are limited. Objectives: The objective of this observational study is to assess the relationship among ACEI or ARB use, preservation of residual renal function (RRF), and CV outcomes and death (cause specific and all-cause) in patients initiating PD. We will further explore any potential inter-clas differences in the association between ACEI vs. ARB use and these outcomes. Our first aim is to assess potential correlates of ACEI or ARB use. Candidate factors include demographic characteristics, concurrent co-morbid conditions, dialysis characteristics, and provider factors. Our second aim is to define the association between ACEI or ARB use and preservation of RRF, which will be calculated as the average of the 24 hour creatinine and urea clearances. We hypothesize that ACEI or ARB use will be associated with better preservation of RRF. We will also examine whether known determinants of loss of RRF modify this association. Our third aim is to evaluate the associations among ACEI or ARB use and the risk of CV outcomes, including myocardial infarction, hospitalization for heart failure, and cardiac cause of death, and all-cause mortality. We hypothesize that use of ACEI or ARB will be associated with lower rates of these outcomes. We will additionally study whether RRF (any vs. none) modifies these associations. Methods: We will use 2 data sources: A) electronic medical records of DaVita, Inc., will contain update medication lists as well as detailed information on vital signs and laboratory measurements; B) the U.S. Renal Data System. The first aim will employ modified multivariable Poisson regression to test for any cross-sectional associations at 90 days after dialysis initiatio between ACEI or ARB use and numerous candidate characteristics. For our second and third aims, we will use multivariable time-to-event analyses to assess the associations between ACEI or ARB use and the clinical events of interest. We will further employ advanced statistical methods, including propensity score techniques; marginal structural models; instrumental variable analyses; repeated measures regression; missing data analysis and imputation; and competing risk models. Significance: Our research will capitalize on an unusually large and detailed dataset of patients initiating PD. In light of limited evidence supporting the use of ACEI or ARB in patients undergoing PD, additional studies are sorely needed, especially based on cohorts of typical patients in usual care settings. Further, the size of the database will allow us to study relevant patient subgroups. PUBLIC HEALTH RELEVANCE: Peritoneal dialysis is a life-saving treatment for many Americans with life-threatening end-stage renal disease. Results of our research may lead to routine use of a class of medication that has the potential to improve their health.

描述（由申请人提供）：对于未进行透析的慢性肾病患者，血管紧张素转换酶抑制剂（ACEI）和血管紧张素-II 受体阻滞剂（ARB）可减缓糖尿病肾病的进展并降低心血管（CV）风险。然而，有关其对腹膜透析（PD）患者有效性的数据有限。目的：本观察性研究的目的是评估开始 PD 的患者使用 ACEI 或 ARB、保留残余肾功能 (RRF) 以及 CV 结局和死亡（特定原因和全因）之间的关系。我们将进一步探讨 ACEI 与 ARB 使用与这些结果之间关联的任何潜在的类间差异。我们的首要目标是评估 ACEI 或 ARB 使用的潜在相关性。候选因素包括人口特征、并发共病、透析特征和提供者因素。我们的第二个目标是确定 ACEI 或 ARB 的使用与保留 RRF 之间的关联，RRF 将以 24 小时肌酐和尿素清除率的平均值计算。我们假设 ACEI 或 ARB 的使用与更好地保存 RRF 相关。我们还将研究 RRF 损失的已知决定因素是否会改变这种关联。我们的第三个目标是评估 ACEI 或 ARB 使用与心血管结局风险之间的关联，包括心肌梗塞、心力衰竭住院、心脏死亡和全因死亡死亡。我们假设使用 ACEI 或 ARB 会降低这些结果的发生率。我们还将研究 RRF（任何与无）是否会改变这些关联。方法：我们将使用 2 个数据源：A) DaVita, Inc. 的电子病历，将包含更新的药物清单以及生命体征和实验室测量的详细信息； B) 美国肾脏数据系统。第一个目标将采用改进的多变量泊松回归来测试透析开始后 90 天的 ACEI 或 ARB 使用与众多候选特征之间的任何横截面关联。对于我们的第二个和第三个目标，我们将使用多变量事件时间分析来评估 ACEI 或 ARB 使用与感兴趣的临床事件之间的关联。我们将进一步采用先进的统计方法，包括倾向评分技术；边际结构模型；工具变量分析；重复测量回归；缺失数据分析和估算；和竞争风险模型。意义：我们的研究将利用异常庞大且详细的帕金森病患者数据集。鉴于支持使用 ACEI 的证据有限或 ARB 治疗 PD 患者，迫切需要进行更多研究，特别是基于常规护理环境中的典型患者队列。此外，数据库的大小将允许我们研究相关的患者亚组。公共卫生相关性：对于许多患有危及生命的终末期肾病的美国人来说，腹膜透析是一种挽救生命的治疗方法。我们的研究结果可能会导致人们常规使用一类有潜力改善健康的药物。