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Reply to: angiotensinogen: a new era beyond lactate as a biomarker?
Critical Care ( IF 8.8 ) Pub Date : 2024-12-16 , DOI: 10.1186/s13054-024-05183-9
Mark C. Chappell, Christopher L. Schaich, Ashish K. Khanna

Dear Editor,

We appreciate the comments from Drs. Shen and Ding [1] regarding our brief research report, “Stronger association of intact angiotensinogen with mortality than lactate or renin in critical illness: post-hoc analysis from the VICTAS trial [2]. Their letter addresses several excellent points about the extent and severity of septic shock in the VICTAS cohort in relation to serum lactate. We agree that the serum levels of lactate were not excessively elevated in our patient population which likely reflects the fact that most of the VICTAS patients were not in severe septic shock. Nonetheless, there was significant mortality in this cohort of sepsis patients that was strongly associated with circulating levels of intact angiotensinogen, suggesting under these conditions that intact angiotensinogen as a biomarker outperformed both renin and lactate according to model performance metrics including area under the curve and the Youden index. Thus, we believe intact angiotensinogen may constitute an additional clinical tool in the care of patients in early sepsis or septic shock. We previously showed that active renin also associated with mortality in this cohort consistent with the recent literature that renin may be a predictor of disease severity that outperforms lactate, as well as a potential indicator for exogenous Ang II treatment to maintain blood pressure and tissue perfusion [3,4,5]. As renin converts angiotensinogen to Ang I and then Ang II through ACE, our results suggest that reduced levels of intact angiotensinogen through excessive renin activity and/or impaired synthesis may also be an indicator of disease severity and may further reveal the need for exogenous Ang II therapy in sepsis patients. The accurate and rapid assessment of plasma Ang II levels is not currently feasible, whereas assay of intact angiotensinogen and active renin or their combination may be a more suitable point-of-care test for critical care patients [2]. We also agree that additional time points in the course of disease are necessary in the assessment of angiotensinogen and other components of the renin–angiotensin–aldosterone system (RAAS) in the critically ill, as well as more detailed assessment of optimal clinical thresholds for each. Indeed, a clinical trial in septic shock patients that directly arose from our present study is currently under way at Wake Forest University School of Medicine that is designed to address several of the issues raised by Drs. Shen and Ding regarding the response of the circulating RAAS and serum lactate.

No datasets were generated or analysed during the current study.

Shen Y, Ding X. Angiotensinogen: a new era beyond lactate as a biomarker? Crit Care. 2024. https://doi.org/10.1186/s13054-024-05164-y.
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Chappell MC, Schaich CL, Busse LW, Martin GS, Sevransky JE, Hinson JK, Khanna AK. Vitamin C TSiSI: stronger association of intact angiotensinogen with mortality than lactate or renin in critical illness: post-hoc analysis from the VICTAS trial. Crit Care. 2024;28(1):333. https://doi.org/10.1186/s13054-024-05120-w.
Article PubMed PubMed Central Google Scholar
Busse LW, Schaich CL, Chappell MC, McCurdy MT, Staples EM, Ten Lohuis CC, et al. Association of active renin content with mortality in critically Ill patients: a post hoc analysis of the vitamin c, thiamine, and steroids in sepsis (VICTAS) trial. Crit Care Med. 2024;52:441–51.
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Weinberger J, Klompas M, Rhee C. What is the utility of measuring lactate levels in patients with sepsis and septic shock? Semin Respir Crit Care Med. 2021;42:650–61.
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Jeyaraju M, McCurdy MT, Levine AR, Devarajan P, Mazzeffi MA, Mullins KE, et al. Renin kinetics are superior to lactate kinetics for predicting in-hospital mortality in hypotensive critically Ill patients. Crit Care Med. 2022;50:50–60.
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Authors and Affiliations

Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, NC, 27101, USA
Mark C. Chappell, Christopher L. Schaich & Ashish K. Khanna
Department of Anesthesiology, Section On Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Ashish K. Khanna
Outcomes Research Consortium, Cleveland, OH, USA
Ashish K. Khanna

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Mark C. ChappellView author publications
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Christopher L. SchaichView author publications
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M.C.C.,C.L.S., and A.K.K., all prepared and wrote this manuscript text. All authors reviewed and approved this final manuscript.

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Correspondence to Mark C. Chappell.

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Chappell, M.C., Schaich, C.L. & Khanna, A.K. Reply to: angiotensinogen: a new era beyond lactate as a biomarker?. Crit Care 28, 407 (2024). https://doi.org/10.1186/s13054-024-05183-9

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Received: 14 November 2024
Accepted: 18 November 2024
Published: 16 December 2024
DOI: https://doi.org/10.1186/s13054-024-05183-9

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中文翻译：

回复：血管紧张素原：超越乳酸作为生物标志物的新时代？

尊敬的编辑：

我们感谢 Shen 和 Ding 博士 [1] 对我们的简短研究报告“在危重疾病中，完整血管紧张素原与死亡率的关联比乳酸或肾素更强：VICTAS 试验的事后分析 [2]。他们的信中讨论了 VICTAS 队列中与血清乳酸相关的感染性休克的程度和严重程度的几个极好的观点。我们同意我们的患者群体的血清乳酸水平并未过度升高，这可能反映了大多数 VICTAS 患者没有出现严重的感染性休克这一事实。尽管如此，这组脓毒症患者存在显着的死亡率，这与完整血管紧张素原的循环水平密切相关，表明在这些情况下，根据模型性能指标，包括曲线下面积和约登指数，完整血管紧张素原作为生物标志物的性能优于肾素和乳酸。因此，我们认为完整的血管紧张素原可能构成早期脓毒症或感染性休克患者护理的额外临床工具。我们之前表明，活性肾素也与该队列的死亡率相关，这与最近的文献一致，即肾素可能是疾病严重程度的预测因子，其表现优于乳酸，以及外源性 Ang II 治疗以维持血压和组织灌注的潜在指标 [3,4,5]。当肾素通过 ACE 将血管紧张素原转化为 Ang I，然后转化为 Ang II，我们的结果表明，由于肾素活性过高和/或合成受损而降低的完整血管紧张素原水平也可能是疾病严重程度的一个指标，并可能进一步揭示脓毒症患者需要外源性 Ang II 治疗。目前无法准确、快速地评估血浆 Ang II 水平，而检测完整的血管紧张素原和活性肾素或其联合检测可能是更适合重症诊疗患者的床旁检测 [2]。我们还同意，在危重症患者中评估血管紧张素原和肾素-血管紧张素-醛固酮系统（RAAS）的其他成分，以及更详细地评估每个的最佳临床阈值时，需要病程中的额外时间点。事实上，维克森林大学医学院目前正在进行一项直接源于我们本研究的感染性休克患者的临床试验，旨在解决 Shen 和 Ding 博士提出的关于循环 RAAS 和血清乳酸反应的几个问题。

在当前研究期间没有生成或分析数据集。

血管紧张素原：超越乳酸作为生物标志物的新时代？暴击护理。2024. https://doi.org/10.1186/s13054-024-05164-y。

文章： PubMed PubMed Central Google Scholar
Chappell MC、Schaich CL、Busse LW、Martin GS、Sevransky JE、Hinson JK、Khanna AK。维生素 C TSiSI：在危重疾病中，完整血管紧张素原与死亡率的相关性比乳酸或肾素更强：VICTAS 试验的事后分析。暴击护理。2024;28(1):333.https://doi.org/10.1186/s13054-024-05120-w。

文章： PubMed PubMed Central Google Scholar
Busse LW、Schaich CL、Chappell MC、McCurdy MT、Staples EM、Ten Lohuis CC 等人。危重患者活性肾素含量与死亡率的关联：败血症中维生素 C、硫胺素和类固醇（VICTAS）试验的事后分析。Crit Care Med. 2024;52:441–51.

文章 PubMed 谷歌学术
Weinberger J， Klompas M， Rhee C.测量脓毒症和感染性休克患者的乳酸水平有什么用？2021 年 Semin Respir Crit Care Med;42:650–61.

文章 PubMed 谷歌学术
Jeyaraju M、McCurdy MT、Levine AR、Devarajan P、Mazzeffi MA、Mullins KE 等人。肾素动力学在预测低血压危重患者的院内死亡率方面优于乳酸动力学。Crit Care Med. 2022;50:50–60.

文章 PubMed 谷歌学术

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维克森林大学医学院高血压中心， Winston-Salem， NC， 27101，美国

马克· C·查普尔，克里斯托弗· L·沙伊奇 & 阿希什· K·坎纳
美国北卡罗来纳州温斯顿-塞勒姆维克森林大学医学院麻醉学系重症监护医学科
阿希什·K·坎纳
美国俄亥俄州克利夫兰 Outcomes Research Consortium
阿希什·K·坎纳

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M.C.C.、C.L.S. 和 A.K.K. 都准备并撰写了这份手稿文本。所有作者都审查并批准了这份最终手稿。

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