AimIn a randomized controlled trial, we recently showed that a natriuresis‐guided diuretic approach improved natriuresis and diuresis in patients with acute heart failure (HF). In this pre‐specified analysis, we investigated the association between (worsening) renal function, outcomes and the effect of intensive natriuresis‐guided loop diuretic therapy as compared with standard of care.Methods and resultsThe Pragmatic Urinary Sodium‐based algoritHm in Acute Heart Failure (PUSH‐AHF) trial randomized patients to natriuresis‐guided diuretic therapy or standard of care. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at fixed timepoints, and worsening renal function (WRF) was assessed at 72 h. The primary outcome was the interaction between randomized treatment allocation, baseline eGFR and the dual primary outcome of PUSH‐AHF: total natriuresis at 24 h and time to all‐cause mortality or HF rehospitalization at 180 days. In 309 patients, median baseline eGFR was 53 (35–73) ml/min/1.73 m2, and 58% had eGFR <60 ml/min/1.73 m2. Baseline eGFR did not significantly modify the treatment effect of natriuresis‐guided diuretic therapy on natriuresis at 24 h (p for interaction = 0.730). However, baseline eGFR significantly modified the effect on all‐cause mortality and HF rehospitalization (p for interaction = 0.017): the risk of this second primary outcome was lower in patients with lower eGFR who were randomized to the natriuresis‐guided group. In the natriuresis‐guided arm, eGFR decreased more (−11.0 vs. −6.91 ml/min/1.73 m2; p = 0.002) during the first 3 days, but this effect was attenuated at discharge (−10.3 vs. −8.69 ml/min/1.73 m2; p = 0.38). WRF was more frequently observed in patients randomized to natriuresis‐guided treatment, but was not associated with worse clinical outcomes.ConclusionsNatriuresis‐guided diuretic treatment improved diuresis and natriuresis irrespective of baseline eGFR and occurrence of WRF, was effective even in patients with low eGFR, and the observed effect on eGFR was transient and not associated with worse clinical outcomes.

中文翻译：

---

肾功能和尿钠引导利尿治疗——来自 PUSH-AHF 试验的预先指定分析

目的在一项随机对照试验中，我们最近表明，排钠引导的利尿方法改善了急性心力衰竭（HF）患者的排钠和利尿作用。在这项预先指定的分析中，我们研究了（恶化的）肾功能、结果以及与标准护理相比强化钠尿引导袢利尿疗法的效果之间的关联。方法和结果基于实用尿钠的算法治疗急性心力衰竭(PUSH-AHF) 试验将患者随机分配接受尿钠引导利尿治疗或标准护理。在固定时间点评估血清肌酐和估计肾小球滤过率（eGFR），并在72小时评估肾功能恶化（WRF）。主要结局是随机治疗分配、基线 eGFR 和 PUSH-AHF 双重主要结局之间的相互作用：24 小时的总尿钠和 180 天的全因死亡率或心衰再住院时间。在 309 名患者中，中位基线 eGFR 为 53 (35–73) ml/min/1.73 m2，58% 的 eGFR <60 ml/min/1.73 m2。基线 eGFR 并未显着改变尿钠引导利尿疗法对 24 小时尿钠排泄的治疗效果（p相互作用 = 0.730)。然而，基线 eGFR 显着改变了对全因死亡率和心力衰竭再住院的影响（p交互作用 = 0.017）：对于随机分配至尿钠引导组的 eGFR 较低的患者，第二个主要结局的风险较低。在钠尿引导组中，eGFR 下降更多（−11.0 vs. -6.91 ml/min/1.73 m2;p= 0.002）在前 3 天，但这种影响在出院时减弱（−10.3 vs. -8.69 ml/min/1.73 m2;p= 0.38）。 WRF 在随机接受尿钠引导治疗的患者中更常见，但与较差的临床结果无关。结论 尿钠引导利尿治疗改善了利尿和尿钠排泄，无论基线 eGFR 和 WRF 的发生情况如何，即使在 eGFR 较低的患者中也是有效的，观察到的对 eGFR 的影响是短暂的，与较差的临床结果无关。