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

基本信息

批准号：
10392416
负责人：
Elaine Ku
金额：
$ 70.06万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/10392416
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 control blood pressure intervention cardiovascular disorder risk clinical decision-making clinical practice data harmonization evidence base experience hemodynamics high risk hypoperfusion improved inhibitor innovation intervention delivery long-term sequelae mortality novel predictive modeling randomized trial rate of change response therapy outcome tool uptake

项目摘要

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.

项目摘要慢性肾病 (CKD) 与显着的发病率和死亡率相关：医疗保险支出 980 亿美元 2017 年用于 CKD 护理的美元。迄今为止，两种干预措施已被证明可以改善心血管疾病降低 CKD 疾病 (CVD) 风险或减缓 CKD 进展的方法是大力降低收缩压 (BP) <120 mmHg 或使用肾素血管紧张素系统 (RAS) 阻滞剂。然而，在两次干预期间，急性大多数患者的估计肾小球滤过率 (eGFR) 会下降，尤其是在基线情况下存在 CKD。传统上，肾功能的这些急性下降（例如血清肌酐增加高达 RAS阻断期间的30%）被认为是良性的、可逆的，并且与长期无关后遗症，但最近的研究质疑肾功能是否会发生更小的变化这些干预措施可能与长期心血管疾病或肾脏风险有关。很少有研究系统地量化了血压降低或 RAS 启动期间 eGFR 急剧下降的程度，以及是否存在可能与较高的不良肾脏或心血管疾病结局风险相关的阈值。这个问题是意义重大，因为目前，适当的血压控制和 RAS 抑制剂的使用在尽管这些干预措施已被证明有益处，但仍对 CKD 患者进行治疗。许多医疗服务提供者可能会放松血压控制或尽管专家建议耐受这些药物，但在 eGFR 急剧下降时停止使用 RAS 抑制剂变化。我们的目标是确定急性变化对肾脏和心血管疾病的长期影响抗高血压治疗期间的 eGFR。在目标 1 中，我们将收集和协调已完成的数据强化血压控制或 RAS 抑制的随机试验在个体水平元研究中检验这个问题分析基线 CKD 患者并确定处于病情急剧下降风险的患者的特征 BP 治疗期间的肾功能。在目标 2 中，我们将评估 eGFR 急性变化之间的关联以及强化降压或 RAS 启动后发生 ESRD 或 CVD 事件的风险，并探讨是否存在与不良后果相关的 eGFR 变化幅度。接下来我们将判断是否 eGFR 的急性变化改变或介导强化降压或 RAS 治疗对 ESRD 的影响或 CVD 风险（目标 3）。最后，我们将开发一种创新工具，1) 预测 eGFR 的进一步变化持续抗高血压治疗，2) 提供 ESRD 或 CVD 风险的精确估计，解释 eGFR 发生的变化（目标 4）。该提案意义重大，可以指导临床决策：如果 eGFR 急剧下降与不良结果无关，那么提供者无论 eGFR 是否发生急性变化，都应鼓励继续这些治疗。然而，如果 eGFR 急剧下降与不良后果相关（以及风险开始时的阈值）增加低于可接受的阈值），那么对这些干预措施的生物反应可以是被认为有助于以循证方式指导临床决策并改善护理。