Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan–Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future.

中文翻译：

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在危重症患者中，完整血管紧张素原与死亡率的相关性强于乳酸或肾素：VICTAS 试验的事后分析


尽管采取了最好的治疗措施，脓毒症和感染性休克仍然是与高死亡率相关的全球医疗保健问题。循环生物标志物可以识别那些有不良结局风险的患者，但是，目前的生物标志物，最突出的是乳酸，是非特异性的，并且对预后和/或疾病管理的影响不一致。肾素-血管紧张素系统 （RAS） 的激活是脓毒症患者的早期事件，循环肾素水平升高比乳酸更能预测更差的结果。前体蛋白血管紧张素原是循环 RAS 的另一个关键成分;它是肾素唯一已知的底物，也是血管加压药血管紧张素 II （Ang II） 的最终来源。我们假设较低的血管紧张素原浓度可能反映了功能失调的 RAS，其特征是高肾素浓度但减弱了 Ang II 生成，这与高肾素反应不成比例，并且可能损害脓毒症患者对血压和组织灌注的充分支持。目前的研究通过受试者工作特征 （ROC） 和 Kaplan-Meier 曲线分析，比较了血清血管紧张素原与死亡率与脓毒症患者基线（第 0 天）血清血管紧张素原与死亡率与乳酸和肾素之间的相关性。在脓毒症患者中，血管紧张素原的血清浓度与 30 天死亡率的相关性比肾素或乳酸的血清浓度更强。此外，血管紧张素原的临床评估可能比肾素的典型测量具有明显的优势。完整血管紧张素原的评估可能有助于更精确的治疗方法（包括外源性血管紧张素 II）来恢复功能失调的 RAS 并改善患者预后。 未来显然需要对该生物标志物进行额外的前瞻性验证研究。