Sepsis-related acute kidney injury: a protective effect of drotrecogin alfa (activated) treatment?

Background: Drotrecogin alfa activated (DrotAA) is licensed for treatment of patients with severe sepsis and organ failure. Among the latter, acute kidney injury (AKI), defined as the persistence of oligo-anuria following adequate resuscitation, is one of the most apprehended. We conducted a prospective, observational, and controlled study to test the hypothesis that DrotAA beneficially affected the evolution and outcome of AKI, complicating acute sepsis-induced cardiopulmonary failure. Methods: Forty-six patients were studied. Thirty subjects received standard treatment for sepsis without DrotAA. In the remaining 16 patients, DrotAA was added as a continuous infusion of 24 mu g/kg/h for 96 h. Results: Mean age, causes of sepsis, and severity/organ failure scores were comparable between patients treated with or without DrotAA. Mortality at 28 days was high and comparable between both treatment groups (56% vs. 69%, DrotAA vs. no DrotAA; P=0.5). When oligo-anuria was present at the start of the study, it persisted during treatment in all patients, with no significant difference between groups. Both treatment groups presented with baseline mean daily fractional excretion of sodium values > 2% that remained high during the observation period, regardless of whether DrotAA was given or not. Kidney histology showed a preserved renal architecture with tubular necrosis in all specimens. Similar glomerular, tubulo-interstitial, and vascular alterations were present in both treatment groups. Conclusion: In this small cohort of patients with severe sepsis who received adjuvant DrotAA treatment, no effect on urine output, tubular function, or mortality could be demonstrated.