Clinical outcomes of persistent sepsis-associated acute kidney injury in septic shock: a post-hoc analysis of a multicenter prospective cohort study

Sepsis-associated acute kidney injury (SA-AKI) contributes to a large morbidity and mortality burden. While emerging evidence suggests that the trajectory of SA-AKI, such as persistent SA-AKI, is associated with clinical outcomes, their association in septic shock remains unclear. In this multicenter prospective study in 20 ICUs, we investigated the incidence, clinical impact, and risk factors of persistent SA-AK in patients with septic shock requiring high-dose norepinephrine. Persistent SA-AKI was defined as an episode of AKI by KDIGO criteria lasting for at least 48 h in sepsis defined by sepsis-3 criteria. We assessed the association of persistent SA-AKI with clinical outcomes using multivariable Cox proportional hazards and logistic regression models. We also investigated risk factors for persistent SA-AKI. In 257 patients with septic shock, 215 (84%) developed SA-AKI within 48 h of ICU admission, and 111 (43%) progressed to persistent SA-AKI. Patients with persistent SA-AKI had a significantly higher risk of 90-day mortality (adjusted HR, 2.75; 95% CI, 1.39–5.42; P = 0.004) and hospital mortality (adjusted OR, 4.29; 95% CI, 1.87–10.70; P < 0.001) than those with transient SA-AKI. Greater time-weighted average vasoactive-inotropic score was independently associated with the development of persistent SA-AKI (adjusted OR, 1.03; 95% CI, 1.01–1.06; P = 0.03). In patients with septic shock requiring high-dose norepinephrine, persistent SA-AKI is associated with worse clinical outcomes. These findings support the need for further research on risk stratification and targeted interventions based on the trajectory of SA-AKI. The study was registered on UMIN Clinical Trial Registry (UMIN000038302) on November 1, 2019.