Prior Use of Renin-Angiotensin System Inhibitors and Risk of Renal Replacement Therapy in Critically Ill Elderly Patients With Sepsis: A Population-Based Cohort Study

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OBJECTIVES: We sought to estimate the association between chronic use of renin-angiotensin system inhibitors and acute kidney injury requiring renal replacement therapy in critically ill adult patients with sepsis. DESIGN: Population-based cohort study in Ontario, Canada. SETTING: ICUs in Ontario, Canada, between April 2008 and March 2019. PATIENTS: Elderly patients admitted to an ICU with a sepsis diagnosis; we excluded patients with established indications of renin-angiotensin system inhibitors. INTERVENTIONS: The prior use (i.e., within 100 d of hospitalization) of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker served as the main exposure of interest; the active comparator was the prior use of calcium channel blockers. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury requiring renal replacement therapy was the primary outcome. Septic shock and all-cause mortality at 30 days served as secondary outcomes. We fitted multivariable modified Poisson regression models to adjust for potential confounders; associations were reported as risk ratios (RRs) alongside 95% CIs. We included 8621 patients, of whom 81% received a renin-angiotensin system inhibitor; mean age was 78 years. Renal replacement therapy was performed in 3.2% of patients; compared with the prior use of a calcium channel blocker, prior use of a renin-angiotensin system inhibitor was associated with a higher risk of acute kidney injury and renal replacement therapy (RR, 1.57; 95% CI, 1.10-2.24), septic shock (RR, 1.18; 95% CI, 1.04-1.33), but not all-cause mortality at 30 days (RR, 0.93; 95% CI, 0.88-1.01). Our results were robust across sensitivity analyses. CONCLUSIONS: Chronic use of a renin-angiotensin system inhibitor is associated with a higher risk of renal replacement therapy and septic shock in adult patients with sepsis.

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