Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA.
Emory Critical Care Center, Emory Healthcare, Atlanta, GA.
Crit Care Med. 2024 Mar 1;52(3):441-451. doi: 10.1097/CCM.0000000000006095. Epub 2023 Nov 10.
Sepsis is a leading cause of mortality. Predicting outcomes is challenging and few biomarkers perform well. Defects in the renin-angiotensin system (RAS) can predict clinical outcomes in sepsis and may outperform traditional biomarkers. We postulated that RAS dysfunction (elevated active renin, angiotensin 1-7 [Ang-(1-7)], and angiotensin-converting enzyme 2 (ACE2) activity with depressed Ang-II and ACE activity) would be associated with mortality in a cohort of septic patients.
Post hoc analysis of patients enrolled in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized controlled trial.
Forty-three hospitals across the United States.
Biorepository samples of 103 patients.
We analyzed day 0 (within 24 hr of respiratory failure, septic shock, or both) and day 3 samples ( n = 103 and 95, respectively) for assessment of the RAS. The association of RAS values with 30-day mortality was determined using Cox proportional hazards regression with multivariable adjustments for age, sex, VICTAS treatment arm, systolic blood pressure, Sequential Organ Failure Assessment Score, and vasopressor use.
High baseline active renin values were associated with higher 30-day mortality when dichotomized to the median of 188.7 pg/mL (hazard ratio [HR] = 2.84 [95% CI, 1.10-7.33], p = 0.031) or stratified into quartiles (Q1 = ref, HR Q2 = 2.01 [0.37-11.04], HR Q3 = 3.22 [0.64-16.28], HR Q4 = 5.58 [1.18-26.32], p for linear trend = 0.023). A 1- sd (593.6 pg/mL) increase in renin from day 0 to day 3 was associated with increased mortality (HR = 3.75 [95% CI, 1.94-7.22], p < 0.001), and patients whose renin decreased had improved survival compared with those whose renin increased (HR 0.22 [95% CI, 0.08-0.60], p = 0.003). Ang-(1-7), ACE2 activity, Ang-II and ACE activity did not show this association. Mortality was attenuated in patients with renin over the median on day 0 who received the VICTAS intervention, but not on day 3 ( p interaction 0.020 and 0.137, respectively). There were no additional consistent patterns of mortality on the RAS from the VICTAS intervention.
Baseline serum active renin levels were strongly associated with mortality in critically ill patients with sepsis. Furthermore, a greater relative activation in circulating renin from day 0 to day 3 was associated with a higher risk of death.
脓毒症是导致死亡的主要原因。预测结局具有挑战性，而且很少有生物标志物表现良好。肾素-血管紧张素系统 (RAS) 的缺陷可以预测脓毒症的临床结局，并且可能优于传统的生物标志物。我们假设在一组脓毒症患者中，RAS 功能障碍（活性肾素升高、血管紧张素 1-7（Ang-(1-7)）和血管紧张素转换酶 2 (ACE2) 活性升高，而 Ang-II 和 ACE 活性降低）与死亡率相关。
维生素 C、硫胺素和固醇治疗脓毒症（VICTAS）随机对照试验的事后分析。
美国 43 家医院。
103 名患者的生物库样本。
我们分析了第 0 天（呼吸衰竭、脓毒性休克或两者发生后 24 小时内）和第 3 天（n = 103 和 95）的样本，以评估 RAS。使用 Cox 比例风险回归分析 RAS 值与 30 天死亡率之间的关系，并对年龄、性别、VICTAS 治疗组、收缩压、序贯器官衰竭评估评分和血管加压药使用进行多变量调整。
高基线活性肾素值与较高的 30 天死亡率相关，当将其分为中位数 188.7 pg/mL 时（风险比 [HR] = 2.84 [95%CI，1.10-7.33]，p = 0.031）或分层为四分位数时（Q1 = 参考，HR Q2 = 2.01 [0.37-11.04]，HR Q3 = 3.22 [0.64-16.28]，HR Q4 = 5.58 [1.18-26.32]，p 趋势= 0.023）。第 0 天至第 3 天肾素增加 1 个标准差（593.6 pg/mL）与死亡率增加相关（HR = 3.75 [95%CI，1.94-7.22]，p < 0.001），并且肾素降低的患者比肾素升高的患者生存率更高（HR 0.22 [95%CI，0.08-0.60]，p = 0.003）。Ang-(1-7)、ACE2 活性、Ang-II 和 ACE 活性没有显示出这种关联。第 0 天肾素高于中位数的患者接受 VICTAS 干预后死亡率降低，但第 3 天没有（p 交互作用 0.020 和 0.137）。VICTAS 干预对 RAS 没有其他一致的死亡率模式。
基线血清活性肾素水平与脓毒症危重症患者的死亡率密切相关。此外，第 0 天至第 3 天循环肾素的相对激活程度与死亡风险增加相关。
