Acute declines in kidney function during blood pressure interventions in CKD

项目摘要 慢性肾脏疾病(CKD)与显著的发病率和死亡率相关：医疗保险花费980亿美元 2017年用于CKD护理的美元。到目前为止，这两项已被证明改善心血管疾病的干预措施 疾病(CVD)风险或延缓CKD的进展是将收缩压(BP)大幅降低至 120毫米汞或使用肾素-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)下降，特别是在基线情况下 CKD是存在的。传统上，这些肾功能的急剧下降(例如，血清肌酐升高高达 30%在RAS封锁期间)被认为是良性的、可逆的，与长期 后遗症，但最近的研究质疑在治疗过程中肾功能是否有更小的变化 这些干预措施可能与长期的心血管疾病或肾脏风险有关。很少有研究系统地 量化降压或RAS启动期间EGFR急剧下降的幅度，以及是否存在 这一阈值可能与肾脏或心血管疾病预后不良的风险较高有关。这个问题是 重要的是，由于目前适当的BP控制和RAS抑制剂的使用在 尽管这些干预措施证明了这些干预措施的好处，但仍有CKD患者。许多供应商可能会放松对BP的控制或 在EGFR急剧下降的情况下停用RAS抑制剂，尽管专家建议耐受这些药物 改变。我们的目标是确定急性变化对肾脏和心血管的长期影响。 降压治疗期间的表皮生长因子受体。在目标1中，我们将收集和协调已完成的数据 强化BP控制或RAS抑制的随机试验在个体水平的Meta-Mate中检查这一问题 分析慢性肾脏病患者的基线情况，并确定有可能在以下方面出现大幅急性下降的患者的特征 血压治疗期间的肾功能。在目标2中，我们将评估EGFR的急性变化之间的关系 以及在密集降压或RAS启动后发生ESRD或CVD事件的风险，并探索是否存在 与不良后果相关的EGFR的变化幅度。接下来，我们将确定是否 EGFR的急性变化改变或调节强化降压或RAS治疗对终末期肾病的影响 或心血管疾病风险(目标3)。最后，我们将开发一种创新的工具，它将1)预测EGFR的进一步变化 通过持续的降压治疗，以及2)提供对终末期肾病或心血管疾病风险的精确估计， 说明发生的EGFR变化(目标4)。这项建议意义重大，因为它可以指导 临床决策：如果EGFR的急剧下降与不良结果无关，那么提供者 应鼓励继续这些治疗，不管发生的急性EGFR变化。 然而，如果EGFR的急剧下降与不良结局(以及风险开始时的阈值)相关 增加低于可接受的阈值)，则对这些干预措施的生物反应可能是 被认为有助于以循证方式指导临床决策并改善护理。

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.