Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock a clinical trial

Rinaldo Bellomo, Lui G. Forni, Laurence W. Busse, Michael T. McCurdy, Kealy R. Ham, David W. Boldt, Johanna Hästbacka, Ashish K. Khanna, Timothy E. Albertson, James Tumlin, Kristine Storey, Damian Handisides, George F. Tidmarsh, Lakhmir S. Chawla, Marlies Ostermann

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1253-1261
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number9
StatePublished - Nov 1 2020


  • Angiotensin I
  • Angiotensin-converting enzyme defect
  • Distributive shock
  • Renin–angiotensin–aldosterone system

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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