Discontinuation of Renin-Angiotensin System Inhibitors during Acute Kidney Injury Episode and All-cause Mortality: Target Trial Emulation Studies.

BACKGROUND Renin-angiotensin system inhibitors (RASi) are widely used among patients with cardiovascular disease, diabetes, and chronic kidney disease, which are high-risk population for AKI. Evidence for the optimal management of RASi during an episode of acute kidney injury (AKI) is lacking. METHODS We conducted a multi-database cohort study using sequential target trial emulation framework from the China Renal Data System (CRDS) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases. Adult patients with hospital-acquired AKI who had been receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) treatment for at least 90 days were included. The primary outcomes were 30-day and 180-day all-cause mortality. Adjusted cumulative incidences and risk differences were estimated using weighted pooled logistic regression models. RESULTS A total of 27,003 person-trials were identified from the CRDS database (median [IQR] age, 70 [58-78] years; 12,972 [60%] male) and the MIMIC-IV database (median [IQR] age, 73 [63-82] years; 2825 [53%] male). The adjusted cumulative incidence of 30-day all-cause mortality was lower among person-trials with RASi discontinuation within two days after the hospital-acquired AKI than continuation (4.36% vs. 5.91%), with a risk difference of -1.55% (95% confidence interval [CI], -2.43% to -0.55%). Discontinuation of RASi was consistently associated with lower risk of all-cause mortality in the MIMIC-IV database, with similar beneficial associations observed across stratified analyses and multiple sensitivity analyses. CONCLUSIONS In this study, stopping RASi within the first two days of AKI detection was associated with a lower risk of all-cause mortality.