Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure.
Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure.
复制标题
利尿后代偿性肾钠重吸收并不是急性心力衰竭利尿抵抗的主要机制。
DOI：
10.1093/eurheartj/ehab620
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发表时间：
2021
影响因子：
39.3
通讯作者：
Ellison,Davi
中科院分区：
文献类型：
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作者：
Cox,ZacharyL;Rao,VeenaS;Ivey-Miranda,JuanB;Moreno-Villagomez,Julieta;Mahoney,Devin;Ponikowski,Piotr;Biegus,Jan;Turner,JeffreyM;Maulion,Christopher;Bellumkonda,Lavanya;Asher,JenniferL;Parise,Helen;Wilson,PerryF;Ellison,Davi
在健康志愿者中，肾脏在袢利尿剂诱导的钠尿排泄后进行代偿性利尿后钠重吸收（CPDSR），最大限度地减少钠排泄并产生中性钠平衡。CPDSR作为利尿剂抵抗机制外推至非正常血容量人群;然而，其在急性失代偿性心力衰竭（ADHF）中的重要性尚不清楚。方法和结果接受静脉袢利尿剂的利尿剂抵抗机制队列中的ADHF患者（285例患者进行462次给药）接受监督尿液采集，需要立即采集利尿前点尿样，然后收集6小时（利尿剂诱导的尿钠排泄期）和18小时（利尿后期）的尿液。利尿剂给药前即刻的平均当场尿钠浓度[末次利尿剂给药后中位数15 h（13-17）]为64 ± 33 mmol/L，仅4%的患者尿钠偏低（<20 mmol/L），与CPDSR一致。利尿后6小时尿钠排泄量与利尿后18小时自发性尿钠排泄量呈正相关（r= 0.7，P < 0.001）。利尿前尿钠/肌酐比值升高（r= 0.37，P < 0.001）是利尿后自发性尿钠增多的最强预测因子。在随机分配至方案驱动强化利尿治疗的患者亚组（n= 43）中，平均利尿剂诱导的尿钠排泄增加了3倍。在CPDSR预测的自发性尿钠排泄大幅减少，没有变化，利尿后自发性尿钠排泄观察（P= 0.47）。与CPDSR相反，更大的利尿剂诱导的尿钠排泄预示着更大的利尿后自发性尿钠排泄。基础钠亲和力，而不是利尿剂诱导的CPDSR，似乎是高血容量性ADHF中利尿剂诱导和利尿后尿钠排泄的主要决定因素。
AimsIn healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown.Methods and resultsPatients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13–17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r= 0.7,P< 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r= 0.37,P< 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n= 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P= 0.47).ConclusionOn a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.