Acute declines in kidney function during blood pressure interventions in CKD

CKD 血压干预期间肾功能急性下降

• 批准号: 10155481
• 负责人: Elaine Ku
• 金额: $ 72.03万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10155481
• 关键词: Accounting; Achievement; Acute; Acute Renal Failure with Renal Papillary Necrosis; Albuminuria; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benign; Biological; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Caring; Cessation of life; Characteristics; Chronic Kidney Failure; Clinical; Creatinine; Data; Disease Outcome; Disease Progression; Dose; Drops; End stage renal failure; Epidemiology; Event; Exhibits; GTP-Binding Protein alpha Subunits, Gs; Glomerular Filtration Rate; Goals; Heart; Heart failure; Individual; Injury to Kidney; Intervention; Kidney; Kidney Diseases; Mediating; Mediator of activation protein; Medicare; Meta-Analysis; Monitor; Morbidity - disease rate; Myocardial Infarction; Outcome; Participant; Patients; Pharmaceutical Preparations; Population; Provider; Public Health; Randomized; Recommendation; Renal function; Renin-Angiotensin System; Risk; Risk Estimate; Role; Safety; Serum; Signal Transduction; Solid; Stroke; Structural defect; Techniques; Testing; Time; adverse outcome; arm; blood pressure intervention; blood pressure regulation; cardiovascular disorder risk; clinical decision-making; clinical practice; data harmonization; evidence base; experience; hemodynamics; high risk; hypoperfusion; improved; inhibitor/antagonist; innovation; mortality; novel; predictive modeling; randomized trial; rate of change; response; therapy outcome; tool; uptake

PROJECT ABSTRACT Chronic kidney disease (CKD) is associated with significant morbidity and mortality: Medicare spent 98 billion dollars for CKD care in 2017. To date, the two interventions that have been shown to improve cardiovascular disease (CVD) risk or slow the progression of CKD are intensive lowering of systolic blood pressure (BP) to <120 mmHg or use of renin-angiotensin system (RAS) blockers. However, during both interventions, acute declines in estimated glomerular filtration rate (eGFR) occur in the majority of patients, especially if baseline CKD is present. Traditionally, these acute declines in kidney function (e.g. serum creatinine increases of up to 30% during RAS blockade) have been thought to be benign, reversible, and not associated with long-term sequelae, but more recent studies have questioned whether even smaller changes in kidney function during these interventions could be associated with long-term CVD or renal risk. Few studies have systematically quantified the magnitude of acute decline in eGFR during BP lowering or RAS initiation and if there is a threshold that may be associated with higher risk of adverse renal or CVD outcomes. This question is significant, since currently, achievement of appropriate BP control and use of RAS inhibitors is suboptimal in patients with CKD despite the proven benefits of these interventions. Many providers may relax BP control or stop RAS inhibitors in the face of acute declines in eGFR despite expert recommendations to tolerate these changes. Our objective is to determine the long-term kidney and CVD implications of the acute changes in eGFR during anti-hypertensive therapy. In Aim 1, we will assemble and harmonize data from completed randomized trials of intensive BP control or RAS inhibition to examine this issue in an individual-level meta- analysis of patients with baseline CKD and identify characteristics of patients at-risk for large acute declines in kidney function during BP therapy. In Aim 2, we will evaluate the association between acute changes in eGFR and risk of ESRD or CVD events following either intensive BP lowering or RAS initiation and explore if there is a magnitude of change in eGFR that is associated with adverse outcomes. Next, we will determine whether acute changes in eGFR modify or mediate the effect of either intensive BP lowering or RAS therapy on ESRD or CVD risk (Aim 3). Finally, we will develop an innovative tool that will 1) predict further changes in eGFR with continued anti-hypertensive therapy and 2) provide refined estimates of the risk of ESRD or CVD, accounting for the changes in eGFR that occurred (Aim 4). This proposal is significant as it could guide clinical decision-making: if acute declines in eGFR are not associated with adverse outcomes, then providers should be encouraged to continue these therapies regardless of the acute eGFR changes that occur. However, if acute declines in eGFR are associated with adverse outcomes (and the threshold when risk begins to increase is lower than the accepted threshold), then the biological response to these interventions could be considered to help guide clinical decision-making in an evidence-based fashion and improve care.

项目摘要 慢性肾脏疾病（CKD）与显着的发病率和死亡率有关：Medicare花费了980亿 2017年CKD护理的美元。迄今为止，已证明可以改善心血管的两种干预 疾病（CVD）风险或降低CKD的进展是大量降低收缩压（BP） <120 mmHg或使用肾素 - 血管紧张素系统（RAS）阻滞剂。但是，在两种干预措施中，急性 大多数患者的估计肾小球滤过率（EGFR）的下降，尤其是在基线的情况下 CKD存在。传统上，这些急性在肾功能方面下降（例如，血清肌酐增加 RAS封锁期间的30％）被认为是良性，可逆的，并且与长期无关 后遗症，但最近的研究质疑，在肾功能的变化是否较小 这些干预措施可能与长期CVD或肾脏风险有关。很少有系统的研究 量化了BP降低或RAS启动期间EGFR急性下降的大小，并且是否存在 可能与较高的不良肾脏或CVD结果风险有关的阈值。这个问题是 由于目前，具有适当的BP控制和使用RAS抑制剂的意义是显着的。 CKD患者尽管有这些干预措施的良好好处。许多提供商可能会放松BP控制或 尽管专家建议可以容忍这些 更改。我们的目标是确定急性变化的长期肾脏和CVD含义 抗高血压疗法期间的EGFR。在AIM 1中，我们将组装和协调完成的数据 强化BP对照或RAS抑制的随机试验，以在个人级别的元中检查此问题 分析基线CKD患者并确定患者处于危险中的患者特征，以减少大量急性下降 BP治疗期间的肾功能。在AIM 2中，我们将评估EGFR急性变化之间的关联 以及强化BP降低或RAS启动后ESRD或CVD事件的风险，并探索是否存在 EGFR的变化幅度与不良结果有关。接下来，我们将确定是否 EGFR的急性变化修改或介导密集型BP降低或RAS治疗对ESRD的影响 或CVD风险（AIM 3）。最后，我们将开发一种创新工具，该工具将1）预测EGFR的进一步变化 通过持续的抗高血压疗法和2）提供了ESRD或CVD风险的精致估计值 考虑发生EGFR的变化（AIM 4）。该建议很重要，因为它可以指导 临床决策：如果EGFR中的急性下降与不良结果无关，则提供者 不管发生的急性EGFR变化如何，都应鼓励继续这些疗法。 但是，如果EGFR中的急性下降与不良结果有关（以及风险开始时的阈值 要增加低于公认的阈值），那么对这些干预措施的生物反应可能是 被考虑以基于证据的方式有助于指导临床决策并改善护理。