A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery.

BACKGROUND: Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). METHODS: We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative-preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). RESULTS: We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL] 2 /1000 [Q1-Q3, -0.24 to 0.28] vs -0.08 [ng/mL] 2 /1000 [Q1-Q3, -0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL] 2 /1000 [95% confidence interval, CI, -0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. CONCLUSIONS: The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.

Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial.

PURPOSE: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. METHODS: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. RESULTS: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. CONCLUSION: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors.