Discontinuation of Renin-Angiotensin System Inhibitors during Acute Kidney Injury Episode and All-Cause Mortality

Key Points It is uncertain whether the discontinuation of renin-angiotensin system (RAS) improves prognosis among patients during an episode of hospital-acquired AKI. Discontinuation of RAS inhibitors within 2 days after AKI was associated with lower risk of all-cause mortality as compared with continuation. Temporary discontinuation of RAS inhibitors during AKI episodes may improve outcomes in long-term users. Background Renin-angiotensin system inhibitors (RASis) are widely used among patients with cardiovascular disease, diabetes, and CKD, which are high-risk populations for AKI. Evidence for the optimal management of RASi during an episode of AKI is lacking. Methods We conducted a multidatabase cohort study using sequential target trial emulation framework from the China Renal Data System 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 or angiotensin receptor blockers treatment for at least 90 days were included. The primary outcomes were 30- 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 China Renal Data System database (median [interquartile range] age, 70 [58–78] years; 12,972 [60%] male) and the MIMIC-IV database (median [interquartile range] 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 2 days after the hospital-acquired AKI than continuation (4.36% versus 5.91%), with a risk difference of −1.55% (95% confidence interval, −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 2 days of AKI detection was associated with a lower risk of all-cause mortality.