Clinical applications of urinary sodium in heart failure from prognostic marker to clinical tool

IF 3.7 2区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Jeroen Dauw
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Although UNa has only recently entered clinical heart failure care, it is gaining recognition as a prognostic marker, as shown in the current analysis, and is increasingly considered for therapeutic and monitoring applications.<span><sup>2, 3</sup></span></p><p>In this issue, a post-hoc analysis of the Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF (SALT-HF) trial examines the association between early natriuretic response and 30-day clinical outcomes in ambulatory patients with worsening heart failure.<span><sup>4</sup></span> SALT-HF was a randomized trial investigating the effect of adding hypertonic saline to intravenous loop diuretics in this population.<span><sup>5, 6</sup></span> The authors evaluated UNa and urine output collected over 3 h following intravenous loop diuretic administration and observed that low UNa, but not low urine volume, was independently associated with higher risk of adverse outcomes, including death, hospitalization, or need for repeat IV diuretics. These results reinforce the idea that natriuresis may reflect more meaningful decongestion than diuresis alone, in terms of both alignment with underlying pathophysiology and its association with outcomes.</p><p>However, several considerations temper the interpretation of these findings. Most importantly, 30-day outcomes are influenced by multiple factors beyond the initial response to therapy. The impact of treatment adjustments, outpatient follow-up and changes in disease trajectory likely play a significant role and were not fully captured. Furthermore, the inclusion of hypertonic saline in half of the population may have influenced natriuretic response, and no subgroup analysis according to treatment arm was performed. Finally, although three-hour urine collections are pragmatic, they may not reflect the full duration of loop diuretic action, which typically peaks between 4 and 6 h.</p><p>From a mechanistic perspective, these findings support the concept that sodium retention is the primary driver of congestion in heart failure, with fluid accumulation occurring as a secondary consequence. This underlines the relevance of targeting natriuresis rather than fluid loss. In a subanalysis of the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) study, patients with low urinary sodium excretion had worse outcomes even when achieving a negative fluid balance,<span><sup>7</sup></span> suggesting that UNa more directly reflects the pathophysiological processes underlying congestion and may be the best target for decongestion.</p><p>Although the SALT-HF analysis was observational, it aligns with prior data showing that early natriuresis is a meaningful prognostic marker both as a single sample value as when assessed serially during decongestion.<span><sup>3, 8</sup></span> More importantly, there is the growing body of evidence suggesting that UNa may serve not only as an indicator but also as a modifiable parameter in treatment decision-making.<span><sup>2</sup></span> The use of UNa to guide diuretic response is already supported by the 2021 ESC heart failure guidelines.<span><sup>9</sup></span> Furthermore, interventional studies such as the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study<span><sup>10, 11</sup></span> and Pragmatic Urinary Sodium-based AlgoritHm in Acute Heart Failure (PUSH-AHF) study<span><sup>12</sup></span> have shown that structured diuretic protocols guided by early UNa response lead to more effective and timely decongestion. While these trials did not demonstrate improvements in hard endpoints, they proved that UNa-guided therapy is feasible and safe and leads to meaningful changes in management. This concept was extended in the Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY-HF) trial, which applied a nurse-led diuretic algorithm based on UNa in the acute hospital setting, improving congestion scores through standardized, protocolised care.<span><sup>13</sup></span></p><p>Another area of interest has been the use of UNa as an outpatient monitoring tool to detect congestion early. As neurohormonal activation directly impairs renal sodium excretion, a drop in UNa might be expected early before clinical signs occur. In an observational study, morning UNa sodium remained stable over 30 weeks, but a drop was noticed 1 week before an acute heart failure episode occurred.<span><sup>14</sup></span> In addition, the Readily Available Urinary Sodium Analysis to Stop Loop Diuretics in Patients with Heart Failure (EASY-STOP) study evaluated UNa in the ambulatory setting to monitor patients after diuretic withdrawal.<span><sup>15</sup></span> A failure to increase first void UNa after reducing or stopping diuretics appeared to identify patients who did not tolerate diuretic withdrawal. This suggests a potential role for UNa, with a drop of UNa as an early warning signal in chronic heart failure management. Although outpatient monitoring is an appealing application of UNa, interventional studies are needed to determine its exact role and value in clinical practice.</p><p><i>Figure</i> 1 summarizes the potential clinical applications of UNa in heart failure. 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引用次数: 0

Abstract

Sodium plays a central role in the pathophysiology of heart failure, where its retention drives congestion and volume overload.1 Urinary sodium (UNa) provides direct insight into renal sodium handling and reflects the combined influence of neurohormonal activation, renal perfusion and tubular function; all of which are central to the syndrome. Although UNa has only recently entered clinical heart failure care, it is gaining recognition as a prognostic marker, as shown in the current analysis, and is increasingly considered for therapeutic and monitoring applications.2, 3

In this issue, a post-hoc analysis of the Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF (SALT-HF) trial examines the association between early natriuretic response and 30-day clinical outcomes in ambulatory patients with worsening heart failure.4 SALT-HF was a randomized trial investigating the effect of adding hypertonic saline to intravenous loop diuretics in this population.5, 6 The authors evaluated UNa and urine output collected over 3 h following intravenous loop diuretic administration and observed that low UNa, but not low urine volume, was independently associated with higher risk of adverse outcomes, including death, hospitalization, or need for repeat IV diuretics. These results reinforce the idea that natriuresis may reflect more meaningful decongestion than diuresis alone, in terms of both alignment with underlying pathophysiology and its association with outcomes.

However, several considerations temper the interpretation of these findings. Most importantly, 30-day outcomes are influenced by multiple factors beyond the initial response to therapy. The impact of treatment adjustments, outpatient follow-up and changes in disease trajectory likely play a significant role and were not fully captured. Furthermore, the inclusion of hypertonic saline in half of the population may have influenced natriuretic response, and no subgroup analysis according to treatment arm was performed. Finally, although three-hour urine collections are pragmatic, they may not reflect the full duration of loop diuretic action, which typically peaks between 4 and 6 h.

From a mechanistic perspective, these findings support the concept that sodium retention is the primary driver of congestion in heart failure, with fluid accumulation occurring as a secondary consequence. This underlines the relevance of targeting natriuresis rather than fluid loss. In a subanalysis of the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) study, patients with low urinary sodium excretion had worse outcomes even when achieving a negative fluid balance,7 suggesting that UNa more directly reflects the pathophysiological processes underlying congestion and may be the best target for decongestion.

Although the SALT-HF analysis was observational, it aligns with prior data showing that early natriuresis is a meaningful prognostic marker both as a single sample value as when assessed serially during decongestion.3, 8 More importantly, there is the growing body of evidence suggesting that UNa may serve not only as an indicator but also as a modifiable parameter in treatment decision-making.2 The use of UNa to guide diuretic response is already supported by the 2021 ESC heart failure guidelines.9 Furthermore, interventional studies such as the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study10, 11 and Pragmatic Urinary Sodium-based AlgoritHm in Acute Heart Failure (PUSH-AHF) study12 have shown that structured diuretic protocols guided by early UNa response lead to more effective and timely decongestion. While these trials did not demonstrate improvements in hard endpoints, they proved that UNa-guided therapy is feasible and safe and leads to meaningful changes in management. This concept was extended in the Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY-HF) trial, which applied a nurse-led diuretic algorithm based on UNa in the acute hospital setting, improving congestion scores through standardized, protocolised care.13

Another area of interest has been the use of UNa as an outpatient monitoring tool to detect congestion early. As neurohormonal activation directly impairs renal sodium excretion, a drop in UNa might be expected early before clinical signs occur. In an observational study, morning UNa sodium remained stable over 30 weeks, but a drop was noticed 1 week before an acute heart failure episode occurred.14 In addition, the Readily Available Urinary Sodium Analysis to Stop Loop Diuretics in Patients with Heart Failure (EASY-STOP) study evaluated UNa in the ambulatory setting to monitor patients after diuretic withdrawal.15 A failure to increase first void UNa after reducing or stopping diuretics appeared to identify patients who did not tolerate diuretic withdrawal. This suggests a potential role for UNa, with a drop of UNa as an early warning signal in chronic heart failure management. Although outpatient monitoring is an appealing application of UNa, interventional studies are needed to determine its exact role and value in clinical practice.

Figure 1 summarizes the potential clinical applications of UNa in heart failure. UNa can be used as a prognostic marker to stratify risk, as a therapeutic parameter to assess diuretic response and adjust therapy and is being explored as a potential tool to detect early signs of decompensation in ambulatory follow-up.

In summary, UNa offers a simple and clinically relevant parameter with both prognostic and therapeutic value. The SALT-HF data confirm its prognostic significance and support further integration into hospital-based diuretic protocols and post-discharge care strategies. Although the study did not evaluate treatment guidance directly, the results strengthen the idea that UNa serves as a practical tool to connect underlying pathophysiology with real-time clinical decision-making.

No funding was provided for this editorial.

JD received speaker fees from AstraZeneca, Bayer, Boehringer-Ingelheim, and Novartis and travel grants from AstraZeneca, Bayer and Daiichi Sankyo.

Abstract Image

尿钠在心力衰竭中的临床应用——从预后指标到临床工具。
钠在心力衰竭的病理生理中起着核心作用,钠的潴留导致充血和容量超载尿钠(UNa)提供了对肾钠处理的直接洞察,反映了神经激素激活、肾灌注和肾小管功能的综合影响;所有这些都是该综合征的核心。尽管UNa最近才进入临床心力衰竭治疗,但正如目前的分析所示,它作为一种预后标志物正在获得认可,并越来越多地考虑用于治疗和监测应用。在这期杂志中,一项对流动心衰患者高渗盐水治疗疗效的事后分析(SALT-HF)试验探讨了急性心衰流动患者早期利钠反应与30天临床结果之间的关系SALT-HF是一项随机试验,研究在静脉循环利尿剂中加入高渗盐水的效果。5,6作者评估了静脉循环利尿剂给药后3小时内收集的UNa和尿量,并观察到低UNa,而不是低尿量,与较高的不良结局风险独立相关,包括死亡、住院或需要重复静脉利尿剂。这些结果强化了这样一种观点,即尿钠可能比利尿更能反映出有意义的去充血,这既符合潜在的病理生理学,也与结果相关。然而,一些考虑因素缓和了对这些发现的解释。最重要的是,除了对治疗的最初反应外,30天的结果还受到多种因素的影响。治疗调整、门诊随访和疾病轨迹变化的影响可能发挥了重要作用,但没有完全被捕获。此外,在半数人群中加入高渗盐水可能会影响尿钠反应,并且没有根据治疗组进行亚组分析。最后,尽管3小时尿液收集是实用的,但它们可能不能反映循环利尿作用的全部持续时间,其通常在4至6小时之间达到峰值。从机制的角度来看,这些发现支持这样的概念,即钠潴留是心力衰竭充血的主要驱动因素,液体积聚是次要后果。这强调了针对钠尿而不是液体流失的相关性。在急性心力衰竭肾脏优化策略评估(roses - ahf)研究的一项亚分析中,尿钠排泄量低的患者即使达到负体液平衡,结果也更差,7表明UNa更直接地反映了充血的病理生理过程,可能是去充血的最佳靶点。尽管SALT-HF分析是观察性的,但它与先前的数据一致,表明早期尿钠是一个有意义的预后标志物,无论是作为单个样本值还是在去充血期间连续评估。更重要的是,越来越多的证据表明,UNa不仅可以作为一个指标,而且可以作为治疗决策的一个可修改的参数2021年ESC心力衰竭指南已经支持使用UNa来指导利尿反应此外,一些介入性研究,如急性心力衰竭标准化利尿剂方案的疗效(act - hf)研究10,11和急性心力衰竭实用尿钠算法(PUSH-AHF)研究12表明,早期UNa反应指导的结构化利尿剂方案可以更有效和及时地缓解充血。虽然这些试验没有证明硬终点的改善,但它们证明了una引导的治疗是可行和安全的,并导致了管理上有意义的改变。这一概念在急性失代偿性心力衰竭患者的尿钠分析(EASY-HF)试验中得到了扩展,该试验在急性医院环境中应用了基于UNa的护士主导的利尿算法,通过标准化的、协议化的护理提高了充血评分。13另一个令人感兴趣的领域是使用UNa作为门诊监测工具来早期发现充血。由于神经激素的激活直接损害肾脏钠的排泄,在出现临床症状之前,UNa可能会下降。在一项观察性研究中,早晨UNa钠在30周内保持稳定,但在急性心力衰竭发作前一周出现下降此外,易获得的尿钠分析用于停止利尿剂在心力衰竭患者中的循环(EASY-STOP)研究评估了UNa在门诊环境中监测利尿剂停药后的患者减少或停用利尿剂后未能增加第一次无效UNa似乎可以确定不能耐受利尿剂停药的患者。 这表明UNa的潜在作用,UNa的下降是慢性心力衰竭管理的早期预警信号。尽管门诊监测是UNa的一个很有吸引力的应用,但需要进行介入性研究来确定其在临床实践中的确切作用和价值。图1总结了UNa在心力衰竭中的潜在临床应用。UNa可作为风险分层的预后标志物,作为评估利尿反应和调整治疗的治疗参数,并且正在探索作为动态随访中发现早期代偿失代偿迹象的潜在工具。综上所述,UNa提供了一个简单且临床相关的参数,具有预后和治疗价值。SALT-HF数据证实了其预后意义,并支持将其进一步纳入以医院为基础的利尿方案和出院后护理策略。虽然该研究没有直接评估治疗指导,但结果加强了UNa作为将基础病理生理学与实时临床决策联系起来的实用工具的观点。没有为这篇社论提供资金。JD获得了阿斯利康、拜耳、勃林格殷格翰和诺华的演讲费,以及阿斯利康、拜耳和第一三共的差旅费。
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来源期刊
ESC Heart Failure
ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine
CiteScore
7.00
自引率
7.90%
发文量
461
审稿时长
12 weeks
期刊介绍: ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.
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