Thrombin-Antithrombin Complex and Fibrinogen Predict Microangiopathic Acute Kidney Injury in Injured Patients

Acute kidney injury (AKI) develops in 20-40% of critically injured patients and contributes to poor outcomes. In sepsis and critical illness, dysregulated coagulation and fibrinolysis are linked to microangiopathic kidney dysfunction, but similar relationships in trauma are not well characterized. We performed a secondary analysis of a single-center randomized controlled trial of severely injured adult trauma patients. Plasma thrombin-antithrombin (TAT), plasmin-2-antiplasmin (PAP), and fibrinogen were measured within 2 hours of injury and 6 hours later. The primary outcome was AKI, defined by the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) criteria. Adjusted logistic regression models evaluated biomarker associations with AKI. Receiver operating characteristic analyses identified discriminatory thresholds. Among 149 patients, 30 (20.1%) developed AKI. Patients with AKI had higher TAT and PAP concentrations and lower fibrinogen levels at both time points. The 6-hour TAT-to-fibrinogen ratio was independently associated with AKI (Adjusted OR 7.17; 95% CI 2.34-21.9, p = 0.001, AUC = 0.88). Supplemental analyses demonstrated consistent associations for TAT and fibrinogen individually, whereas PAP was not independently predictive. A 6-hour TAT level < 99 pg/mL identified patients unlikely to develop AKI (negative predictive value [NPV] 93.9%). Fibrinogen levels > 173 mg/dL showed a low likelihood of AKI (NPV 88.2%). Elevated TAT and reduced fibrinogen measured 6 hours after injury were independently associated with AKI. This suggests that early coagulation imbalance may reflect evolving microvascular kidney dysfunction in injured patients and potentially warrants the evaluation of the TAT-to-fibrinogen ratio as an early marker of trauma-related AKI. (NCT02535949).