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

• 批准号: 8527503
• 负责人: Jenny I Shen
• 金额: $ 6.2万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 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/8527503
• 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

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.

描述（由申请人提供）：对于慢性肾脏疾病而不是透析的患者，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）降低了糖尿病性肾病的进展并降低心血管疾病（CV）风险。但是，关于其在腹膜透析（PD）患者中有效性的数据受到限制。目的：这项观察性研究的目的是评估ACEI或ARB使用之间的关系，剩余肾功能（RRF）以及启动PD的患者中的CV结局和死亡（原因是特定和全因）。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CLAS间差异。我们的第一个目的是评估ACEI或ARB使用的潜在相关性。候选因素包括人口统计学特征，并发合并条件，透析特征和提供者因素。我们的第二个目的是定义ACEI或ARB使用与RRF保存之间的关联，这将计算为24小时肌酐和尿素清除的平均值。我们假设ACEI或ARB使用将与RRF更好地保存有关。我们还将检查RRF丢失的已知决定因素是否修改了该关联。我们的第三个目的是评估ACEI或ARB使用之间的关联以及CV结果的风险，包括心肌梗塞，心力衰竭住院和心脏原因和全因病因 死亡。我们假设使用ACEI或ARB的使用将与这些结果的较低率有关。我们还将研究RRF（任何与无）是否修改了这些关联。方法：我们将使用2个数据来源：a）Davita，Inc。的电子病历，将包含更新的药物清单以及有关生命体征和实验室测量的详细信息； b）美国肾脏数据系统。第一个目标将采用经过修改的多变量泊松回归来测试ACEI或ARB使用与众多候选特征之间透析起步后90天的横截面关联。对于我们的第二和第三目标，我们将使用多变量的事实分析来评估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，包括倾向得分技术；边缘结构模型；仪器变量分析；重复测量回归；缺少数据分析和插补；和竞争风险模型。意义：我们的研究将利用一个异常大而详细的患者数据集发起PD。鉴于支持使用ACEI的有限证据 或接受PD的患者中的ARB，非常需要其他研究，尤其是基于常规护理环境中典型患者的同类。此外，数据库的大小将使我们 研究相关的患者亚组。

项目成果

Renin-angiotensin system blockers and residual kidney function loss in patients initiating peritoneal dialysis: an observational cohort study.

• DOI: 10.1186/s12882-017-0616-4
• 发表时间: 2017-06-17
• 期刊: BMC nephrology
• 影响因子: 2.3
• 作者: Shen JI;Saxena AB;Vangala S;Dhaliwal SK;Winkelmayer WC
• 通讯作者: Winkelmayer WC

Comparative effectiveness of angiotensin receptor blockers vs. angiotensin-converting enzyme inhibitors on cardiovascular outcomes in patients initiating peritoneal dialysis.

血管紧张素受体阻滞剂与血管紧张素转换酶抑制剂对开始腹膜透析患者心血管结局的疗效比较。

• DOI: 10.1007/s40620-016-0340-3
• 发表时间: 2017
• 期刊: Journal of nephrology
• 影响因子: 3.4
• 作者: Shen,JennyI;Saxena,AnjaliB;Montez-Rath,MariaE;Leng,Lynn;Chang,TaraI;Winkelmayer,WolfgangC
• 通讯作者: Winkelmayer,WolfgangC

Correlates and variance decomposition analysis of heparin dosing for maintenance hemodialysis in older US patients.

• DOI: 10.1002/pds.3595
• 发表时间: 2014-05
• 期刊: PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
• 影响因子: 2.6
• 作者: Shen, Jenny I.;Montez-Rath, Maria E.;Mitani, Aya A.;Erickson, Kevin F.;Winkelmayer, Wolfgang C.
• 通讯作者: Winkelmayer, Wolfgang C.