Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial.
Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial.
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DOI：
10.1164/rccm.201911-2172oc
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发表时间：
2020-11-01
影响因子：
24.7
通讯作者：
Ostermann M
中科院分区：
文献类型：
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作者：
Bellomo R;Forni LG;Busse LW;McCurdy MT;Ham KR;Boldt DW;Hästbacka J;Khanna AK;Albertson TE;Tumlin J;Storey K;Handisides D;Tidmarsh GF;Chawla LS;Ostermann M
原理：外源性血管紧张素II可增加儿茶酚胺抵抗性血管舒张性休克（CRVS）患者的平均动脉压。我们假设，肾素浓度可能确定患者最有可能受益于这种治疗。目的：探讨慢性肾功能不全（CRVS）患者血浆肾素浓度的动态变化及其预后价值。研究方法：我们分析了ATHOS-3（血管紧张素II治疗高输出量休克）试验中患者在开始给予血管紧张素II或安慰剂前和3小时后的血清样本中的肾素、血管紧张素I和血管紧张素II浓度。测量和主要结果：255例研究患者中有194例（76%）的基线血清肾素浓度（正常范围，2.13-58.78 pg/ml）高于正常上限，中位肾素浓度为172.7 pg/ml（四分位距[IQR]，60.7 - 440.6 pg/ml），约为正常上限的3倍。肾素浓度与血管紧张素I/II比值呈正相关（r = 0.39; P < 0.001）。开始血管紧张素II治疗后3小时，肾素浓度降低54.3%（IQR，降低37.9%至66.5%），而安慰剂组降低14.1%（IQR，降低37.6%至增加5.1%）（P < 0.0001）。在肾素浓度高于研究人群中位数的患者中，血管紧张素II显著降低了28天死亡率至28/55（50.9%）例患者，而73例患者中有51例（69.9%）接受安慰剂治疗（未分层风险比，0.56; 95%置信区间，0.35 - 0.88; P = 0.012）（相互作用P = 0.048）。结论：血清肾素浓度在CRVS中显著升高，可以识别血管紧张素II治疗对临床结局有有益影响的患者。在www.clinicaltrials.gov注册的临床试验（NCT 02338843）。
Rationale: Exogenous angiotensin II increases mean arterial pressure in patients with catecholamine-resistant vasodilatory shock (CRVS). We hypothesized that renin concentrations may identify patients most likely to benefit from such therapy. Objectives: To test the kinetic changes in renin concentrations and their prognostic value in patients with CRVS. Methods: We analyzed serum samples from patients enrolled in the ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock) trial for renin, angiotensin I, and angiotensin II concentrations before the start of administration of angiotensin II or placebo and after 3 hours. Measurements and Main Results: Baseline serum renin concentration (normal range, 2.13–58.78 pg/ml) was above the upper limits of normal in 194 of 255 (76%) study patients with a median renin concentration of 172.7 pg/ml (interquartile range [IQR], 60.7 to 440.6 pg/ml), approximately threefold higher than the upper limit of normal. Renin concentrations correlated positively with angiotensin I/II ratios (r = 0.39; P < 0.001). At 3 hours after initiation of angiotensin II therapy, there was a 54.3% reduction (IQR, 37.9% to 66.5% reduction) in renin concentration compared with a 14.1% reduction (IQR, 37.6% reduction to 5.1% increase) with placebo (P < 0.0001). In patients with renin concentrations above the study population median, angiotensin II significantly reduced 28-day mortality to 28 of 55 (50.9%) patients compared with 51 of 73 patients (69.9%) treated with placebo (unstratified hazard ratio, 0.56; 95% confidence interval, 0.35 to 0.88; P = 0.012) (P = 0.048 for the interaction). Conclusions: The serum renin concentration is markedly elevated in CRVS and may identify patients for whom treatment with angiotensin II has a beneficial effect on clinical outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 02338843).