Prognosis of critically ill patients with severe acute kidney injury and high circulating dipeptidyl peptidase 3: a post hoc analysis of the AKIKI 2 trial

Acute kidney injury (AKI) is a frequent and severe complication among critically ill patients. Circulating dipeptidyl peptidase 3 (cDPP3), an enzyme released upon cellular injury, has been implicated in hemodynamic instability and organ dysfunction. Its role in severe AKI remains poorly defined. We aimed to assess the prognostic significance of cDPP3 in critically ill patients with severe AKI. In this post hoc analysis of the AKIKI 2 study, we included ICU patients with severe AKI (KDIGO stage 3) who were receiving (or had received) invasive mechanical ventilation and/or vasopressor support and had available blood samples at inclusion. Patients were stratified according to cDPP3 concentration using a predefined cutoff of 40 ng/mL. The primary outcome was 28-day mortality; secondary outcomes were organ support–free days. Among 287 included patients, 143 (49.8%) had cDPP3 concentrations above 40 ng/mL. High cDPP3 was associated with increased 28-day mortality (hazard ratio 1.95; 95% confidence interval 1.37–2.87, p < 0.001). Furthermore, high cDPP3 was associated with fewer days alive without vasopressors (mean difference − 5.59; 95% CI − 8.29 to − 2.78, p < 0.001), invasive mechanical ventilation (mean difference − 6.23; 95% CI − 8.89 to − 3.36, p < 0.001), or renal replacement therapy (mean difference − 6.35; 95% CI − 9.14 to − 3.26, p < 0.001). After adjustment for baseline markers of severity, both the associations with 28-day mortality and organ support-free days remained significant. In critically ill patients with severe AKI, a high cDPP3 concentration at diagnosis is associated with increased short-term mortality and prolonged dependence on organ support.