RAAS Inhibition and Risk of AKI in COVID-19

Background: Direct viral invasion of the kidney via ACE2 has been hypothesized as a mechanism of AKI in COVID-19 (COVID). The impact of RAASi on the risk of AKI in COVID is not known. We hypothesized that active use of RAASi preceding admission would be associated with a greater proportional risk of AKI in COVID than influenza (flu). Methods: In this retrospective cohort, we compared the AKI incidence by RAASi status in 11,898 hospitalized Veterans with COVID or flu between Oct 1, 2019 and Sept 30, 2020. To control for confounding, propensity score weighting balanced baseline conditions, labs, and co-therapies in 4 exposure groups: RAASi users with COVID, non-users with COVID, RAASi users with flu, and non-users with flu. Weighted logistic regression estimated the main effects of RAASi and COVID, and their interaction. Results: In flu, 7% of RAASi users had a stage 2-3 AKI vs 5% of non-users, a 2% increase (p=0.03). In COVID, 16% of RAASi users had a stage 2-3 AKI vs 12% of nonusers, a 4% increase. While the absolute increase in AKI incidence for RAASi users vs non-users was greater in COVID patients vs flu, the difference was not statistically significant (p=0.66) and the RAASi association was proportionally smaller in COVID (see interaction in Table). Similar absolute differences were observed in stage 1-3 AKI (Table), and the interaction was also not statistically significant (p=0.66). Conclusions: COVID was associated with a greater incidence of AKI than flu. RAASi was associated with an increased incidence of Stage 2-3 AKI in patients with COVID or flu. The proportional effect of RAASi was similar in COVID and flu patients. These findings do not support a disproportionate risk of AKI among RAASi users with COVID.