Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock.

RATIONALE 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. OBJECTIVES To test the kinetic changes in renin levels and their prognostic value in CRVS patients. METHODS 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. MEASUREMENTS AND MAIN RESULTS 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). CONCLUSIONS 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/).