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Title: Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock.
Austin Authors: Bellomo, Rinaldo ;Forni, Lui G;Busse, Laurence W;McCurdy, Michael T;Ham, Kealy R;Boldt, David W;Hästbacka, Johanna;Khanna, Ashish K;Albertson, Timothy E;Tumlin, James;Storey, Kristine;Handisides, Damian;Tidmarsh, George F;Chawla, Lakhmir S;Ostermann, Marlies
Affiliation: The University of Melbourne, 2281, Centre for Integrated Critical Care, Department of Medicine & Radiology, Melbourne, Victoria, Australia
Department of Intensive Care, Austin Health, Heidelberg, Victoria, Australia
Monash University, Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Melbourne, Victoria, Australia
Royal Surrey County Hospital NHS Foundation Trust and Faculty of Health Sciences University of Surrey, Department of Intensive Care Medicine, Guildford, United Kingdom of Great Britain and Northern Ireland
Outcomes Research Consortium, Cleveland, Ohio, United States
Wake Forest University School of Medicine, 12279, Department of Anesthesiology, Section on Critical Care Medicine, Winston-Salem, North Carolina, United States
Veterans Affairs Medical Center, Department of Medicine, San Diego, California, United States
La Jolla Pharmaceutical Company, 17726, Chief Medical Officer, San Diego, California, United States
Emory University, 1371, Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Atlanta, Georgia, United States
University of Maryland School of Medicine, 12264, Pulmonary and Critical Care, Baltimore, Maryland, United States
University of Minnesota System, 311816, Pulmonary, Allergy, Critical Care and Sleep Medicine, Minneapolis, Minnesota, United States
University of California Los Angeles, 8783, Department of Anesthesiology and Perioperative Medicine, Division of Critical Care, Los Angeles, California, United States
University of Helsinki and Helsinki University Hospital, Division of Intensive Care Medicine, Department of Perioperative, Intensive Care and Pain Medicine, Helsinki, Finland
University of California, Northern California Health System, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, Mather, California, United States
Emory University Medical Center, Department of Medicine, Renal Division, Atlanta, Georgia, United States
La Jolla Pharmaceutical Company, 17726, Department of Bioanalytics, San Diego, California, United States
La Jolla Pharmaceutical Company, 17726, Department of Biostatistics, San Diego, California, United States
La Jolla Pharmaceutical Company, 17726, Chief Executive Officer, San Diego, California, United States
King's College London, Guy's & St Thomas Hospital, Critical Care, London, United Kingdom of Great Britain and Northern Ireland
Issue Date: 1-Jul-2020 2020-07-01
Publication information: American Journal of Respiratory and Critical Care Medicine 2020; online first: 1 July
Abstract: Exogenous angiotensin II increases mean arterial pressure in patients with catecholamine-resistant vasodilatory shock (CRVS). We hypothesized that renin levels may identify patients most likely to benefit from such therapy. To test the kinetic changes in renin levels and their prognostic value in CRVS patients. We analyzed serum samples from patients enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial for renin, angiotensin I, and angiotensin II levels prior to the start of administration of angiotensin II or placebo and after 3 hours. Baseline serum renin concentration (normal range: 2.13-58.78 pg/ml) was above the upper limits of normal (ULN) in 194/255 (76%) study patients with a median renin concentration of 172.7 pg/mL (interquartile range [IQR]: 60.7-440.6 pg/mL), approximately three-fold higher than ULN. Renin levels correlated positively with angiotensin I/angiotensin II ratios (r =.39; P<0.001). At 3 hours after initiation of angiotensin II therapy, there was a 54.3% reduction (IQR: 37.9%-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 28/55 (50.9%) patients compared with 51/73 patients (69.9%) treated with placebo (unstratified hazard ratio: 0.56; 95% confidence interval: 0.35-0.88; P=0.012) (p = 0.048 for the interaction). 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (
DOI: 10.1164/rccm.201911-2172OC
ORCID: 0000-0002-1650-8939
PubMed URL: 32609011
Type: Journal Article
Subjects: angiotensin I
angiotensin II
angiotensin-converting enzyme defect
distributive shock
renin-angiotensin-aldosterone system
Appears in Collections:Journal articles

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