MO420ROLE OF IL-6 ON ACUTE KIDNEY INJURY (AKI) DEVELOPMENT AFTER LIVER TRANSPLANTATION

Background and Aims Acute kidney injury (AKI) post-liver transplantation is a frequent complication with an incidence up to 70%, requiring renal replacement therapy in about 25% of transplant patients. AKI in patients with normal renal function is a recognized risk factor (FR) of chronic renal failure (CKD) de novo, associated with a 4.5 times greater mortality at 5 years post-transplant. Pathogenesis of AKI is multifactorial. Beyond the classical pre-transplant risk factors, the hypoxia of the graft and the ischemia-reperfusion injury (IRI) have recently been recognized to exert a pathogenetic role with specific mechanisms. It has been recently demonstrated in experimental setting that ischemic tissues put in place protective mechanisms in response to hypoxia aimed at increasing the release of oxygen with the activation of angiogenesis mediated by the expression of factors induced by hypoxia (HIF)-1-alpha. HIF1-alfa has been shown to promote cell survival under hypoxic conditions by switching metabolism from oxidative to glycolytic, by affecting the production of ATP to prevent excessive mitochondrial generation of reactive oxygen species, by promoting secondary release of vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-ß1), with following activation of inflammatory cytokines responsible for systemic inflammatory response syndrome (SIRS). Tumor necrosis factor-α, IL-1 and IL-6 are the most important cytokines released in IRI and seem to play a pivotal role in the onset of AKI in SIRS and sepsis. The development of AKI after hypoxia/ischemia of the graft, as observed more frequently in the population of recipients from donors after cardiocirculatory death (DCD) compared to donation after brain death (DBD), confirms this pathogenetic mechanism. Aim of the study is to evaluate AKI occurrence among liver transplanted patients and its relationship with IRI and cytokines systemic release. Method Data of 78 patients (62 males, 79.5%) undergone liver transplantation (2007-2011) were retrieved. Results The following clinical investigations were performed: AKI patients demonstrated a progressive increasing of IL-6 after liver transplantation (AKI 34.4-37.8-88.2 ng/ml vs no AKI 30.5-21.6-23.3 ng/ml). Conclusion Patients who experienced greater ischaemia-reperfusion injury of the liver graft developed more frequently AKI. Patients with AKI experienced an increased release and circulation of IL-6, that probably is involved in AKI development with interesting implications in future therapy.