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Author Notes:

Rinaldo Bellomo, M.D., Ph.D., Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia. E-mail: rinaldo.bellomo@austin.org.au

Author Contributions: Acquisition of data: R.B., L.W.B., M.T.M., K.R.H., D.W.B., J.H., A.K.K., T.E.A., J.T., K.S., L.S.C., and M.O. Conception and design: R.B. and L.S.C. Analysis and interpretation: R.B., L.G.F., L.W.B., M.T.M., T.E.A., J.T., D.H., G.F.T., L.S.C., and M.O. Wrote the manuscript: R.B., L.G.F., L.S.C., and M.O. Approved and edited the manuscript: R.B., L.G.F., L.W.B., M.T.M., K.R.H., J.H., T.E.A., and L.S.C. All authors approved the final manuscript.

The authors thank the patients and their families for entrusting them to conduct this study. They also thank the study investigators, study coordinators, and support staff across all sites for their compassion, dedication, and diligence in the conduct of this trial. Medical editorial assistance was provided by Robert J. Schoen, PharmD, of ApotheCom (Yardley, Pennsylvania) and funded by La Jolla Pharmaceutical Company (San Diego, California).


Research Funding:

Supported by La Jolla Pharmaceutical Co. (primary study and this post hoc analysis).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Critical Care Medicine
  • Respiratory System
  • General & Internal Medicine
  • angiotensin I
  • renin-angiotensin-aldosterone system
  • distributive shock
  • angiotensin-converting enzyme defect

Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock A Clinical Trial

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Journal Title:



Volume 202, Number 9


, Pages 1253-1261

Type of Work:

Article | Final Publisher PDF


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.

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© 2020 by the American Thoracic Society

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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