Gupta Richa, Testani Jeffrey, Collins Sean
Department of Cardiovascular Medicine, Vanderbilt University Medical Center, 1121 Medical Center Dr., Nashville, TN, 37212, USA.
Department of Cardiovascular Medicine, Yale Medical Center, PO Box 208017, New Haven, CT, 06520, USA.
Curr Heart Fail Rep. 2019 Apr;16(2):57-66. doi: 10.1007/s11897-019-0424-1.
Diuretic resistance (DR) occurs along a spectrum of relative severity and contributes to worsening of acute heart failure (AHF) during an inpatient stay. This review gives an overview of mechanisms of DR with a focus on loop diuretics and summarizes the current literature regarding the prognostic value of diuretic efficiency and predictors of natriuretic response in AHF.
The pharmacokinetics of diuretics are impaired in chronic heart failure, but little is known about mechanisms of DR in AHF. Almost all diuresis after administration of a loop diuretic dose occurs in the first few hours after administration and within-dose DR can develop. Recent studies suggest that DR at the level of the nephron may be more important than defects in diuretic delivery to the tubule. Because loop diuretics induce natriuresis, urine sodium (UNa) concentration may serve as a functional, physiological, and direct measure for diuretic responsiveness to a given loop diuretic dose. Identifying and targeting individuals with DR for more aggressive, tailored therapy represents an important opportunity to improve outcomes. A better understanding of the mechanistic underpinnings of DR in AHF is needed to identify additional biomarkers and guide future trials and therapies.
利尿剂抵抗(DR)存在一系列相对严重程度,并导致住院期间急性心力衰竭(AHF)恶化。本综述概述了利尿剂抵抗的机制,重点关注袢利尿剂,并总结了当前关于利尿剂疗效的预后价值以及AHF中利钠反应预测因素的文献。
慢性心力衰竭患者利尿剂的药代动力学受损,但关于AHF中利尿剂抵抗的机制知之甚少。给予袢利尿剂剂量后,几乎所有利尿作用都发生在给药后的最初几个小时内,且可能会出现剂量内抵抗。最近的研究表明,肾单位水平的利尿剂抵抗可能比利尿剂输送到肾小管的缺陷更为重要。由于袢利尿剂可诱导利钠作用,尿钠(UNa)浓度可作为对给定袢利尿剂剂量的利尿剂反应性的功能性、生理性和直接测量指标。识别并针对利尿剂抵抗个体进行更积极、个性化的治疗是改善预后的重要契机。需要更好地理解AHF中利尿剂抵抗的机制基础,以识别其他生物标志物并指导未来的试验和治疗。