Erythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial.
Skrifvars MB., Moore E., Mårtensson J., Bailey M., French C., Presneill J., Nichol A., Little L., Duranteau J., Huet O., Haddad S., Arabi Y., McArthur C., Cooper DJ., Bellomo R., EPO-TBI Investigators and the ANZICS Clinical Trials Group None.
BACKGROUND:Acute kidney injury (AKI) in traumatic brain injury (TBI) is poorly understood and it is unknown if it can be attenuated using erythropoietin (EPO). METHODS:Pre-planned analysis of patients included in the EPO-TBI (ClinicalTrials.gov NCT00987454) trial who were randomized to weekly EPO (40 000 units) or placebo (0.9% sodium chloride) subcutaneously up to three doses or until intensive care unit (ICU) discharge. Creatinine levels and urinary output (up to 7 days) were categorized according to the Kidney Disease Improving Global Outcome (KDIGO) classification. Severity of TBI was categorized with the International Mission for Prognosis and Analysis of Clinical Trials in TBI. RESULTS:Of 3348 screened patients, 606 were randomized and 603 were analyzed. Of these, 82 (14%) patients developed AKI according to KDIGO (60 [10%] with KDIGO 1, 11 [2%] patients with KDIGO 2, and 11 [2%] patients with KDIGO 3). Male gender (hazard ratio [HR] 4.0 95% confidence interval [CI] 1.4-11.2, P = 0.008) and severity of TBI (HR 1.3 95% CI 1.1-1.4, P < 0.001 for each 10% increase in risk of poor 6 month outcome) predicted time to AKI. KDIGO stage 1 (HR 8.8 95% CI 4.5-17, P < 0.001), KDIGO stage 2 (HR 13.2 95% CI 3.9-45.2, P < 0.001) and KDIGO stage 3 (HR 11.7 95% CI 3.5-39.7, P < 0.005) predicted time to mortality. EPO did not influence time to AKI (HR 1.08 95% CI 0.7-1.67, P = 0.73) or creatinine levels during ICU stay (P = 0.09). CONCLUSIONS:Acute kidney injury is more common in male patients and those with severe compared to moderate TBI and appears associated with worse outcome. EPO does not prevent AKI after TBI.