Rates of AKI with ACE Inhibitor and Angiotensin-Receptor Blocker Use

Background: Nephrotoxic medications are a substantial contributor to in-hospital acute kidney injury (AKI). Studies suggest that angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) are often stopped in the setting of AKI and not resumed on discharge or follow-up, but whether ACEi/ARB should be treated as nephrotoxins is a matter of debate. We hypothesized that among hospitalized patients with high nephrotoxin exposure, receipt of ACEi/ARB would result in similar rates of AKI development as other nephrotoxins. Methods: Adult patients with ≥1 day of high nephrotoxin exposure from 2014-2022 were included. High nephrotoxin exposure was defined according to Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) criteria as ≥3 nephrotoxins on one day or ≥3 days of intravenous vancomycin or aminoglycoside. The primary outcomes were time to any-stage AKI, AKI stage 1b, and AKI stage 2+3. A Cox proportional hazards model accounted for age, race, sex, BMI, comorbidities, baseline creatinine, vancomycin use, ICU care, and clinical parameters (selected lab values and vital signs) on the day of initial high nephrotoxin exposure. Results: A total of 13,826 patients had ≥1 day of high nephrotoxin exposure, of which 2,916 (21%) received an ACEi or ARB as part of their nephrotoxin exposure. The ACEi/ARB group was significantly older (64±14 vs 58±15 years) and more likely to have congestive heart failure (16% vs 9%) and diabetes (22% vs 13%), but less likely to be in the ICU (18% vs 25%) and less likely to receive vancomycin (40% vs 67%). All-stage AKI occurred in 31% in both groups (p=0.6); stage 1b AKI occurred in 18% for ACEi/ARB compared to 21% (p<0.001); stage 2+3 AKI occurred in 5.5% vs 7.8% for non-ACEi/ARB (p<0.001). Adjusted hazard ratios for ACEi/ARB exposure were 0.98 (95% CI 0.90-1.09, p=0.6) for any-stage AKI, 0.90 (95% CI 0.81-1.00, p=0.04) for AKI stage 1b, and 0.83 (95% CI 0.69-0.99, p=0.04) for AKI stage 2+3. Conclusion: Patients receiving two nephrotoxic medications + ACEi/ARB were as likely to develop any-stage AKI as those receiving three nephrotoxic medications (without ACEi/ARB), but had 17% lower hazards for AKI stage 2+3 development.