HEMAKI

Multiorgan failure is a life-threatening complication of severe trauma that commonly affects kidney function and causes acute kidney injury (AKI), a critical condition associated with increased mortality. Although transfusion is the cornerstone of trauma resuscitation and a life-saving therapy, it is associated with an increased risk for AKI independently of trauma severity. Stored red blood cells (RBCs) indeed display altered nitric oxide (NO) homeostasis and may thus impair NO bioavailability following transfusion with a subsequent decrease in tissue perfusion. Moreover, transfusion of stored RBCs is associated with an increase in plasma free hemoglobin (Hb), a toxic breakdown product of RBCs that can promote AKI. Though the mechanisms linking Hb to AKI are incompletely understood, they include kidney pro-inflammatory effects and oxidative stress. Further studies are thus warranted to investigate the underlying mechanisms of RBC and free Hb toxicity especially in the context of severe trauma. By using experimental models of severe trauma (hemorrhagic shock associated with rhabdomyolysis), in vitro models of renal tubular cells exposed to stored RBCs and free Hb, observational study of free Hb changes and RBC function in severe trauma patients, the HEMAKI study proposes a translational approach from cell to bedside that aims 1/ to better understand the specific roles of stored RBCs and free Hb in post-traumatic AKI, 2/to assess whether their actions do interact synergistically with the systemic aggressions commonly encountered in trauma (i.e. hemorrhage, rhabdomyolysis), 3/to propose therapies aiming to curb the renal side-effects of transfusion and hemoproteins in severe trauma. Since transfusion is the basis of trauma resuscitation, translational research aiming to correct the renal microvascular side-effects of stored RBCs and free Hb would have a major positive impact on daily clinical practice.