Ischemia reperfusion injury (IRI) is one of the most important mechanisms involved in delayed or reduced graft function after kidney transplantation. It is a complex pathophysiological process, followed by a pro-inflammatory response that enhances the immunogenicity of the graft and the risk of acute rejection. Many biologic processes are involved in its development, such as transcriptional reprogramming, the activation of apoptosis and cell death, endothelial dysfunction and the activation of the innate and adaptive immune response. Recent evidence has highlighted the importance of complement activation in IRI cascade, which expresses a pleiotropic action on tubular cells, on vascular cells (pericytes and endothelial cells) and on immune system cells. The effects of IRI in the long term lead to interstitial fibrosis and tubular atrophy, which contribute to chronic graft dysfunction and subsequently graft failure. Furthermore, several metabolic alterations occur upon IRI. Metabolomic analyses of IRI detected a “metabolic profile” of this process, in order to identify novel biomarkers that may potentially be useful for both early diagnosis and monitoring the therapeutic response. The aim of this review is to update the most relevant molecular mechanisms underlying IRI, and also to discuss potential therapeutic targets in future clinical practice.

Introduction: The intrarenal resistance index (RI) is a calculated parameter for the assessment of the status of the graft during the follow-up ultrasound of the transplanted kidney. Currently it is still unclear the predictive value of RI, also in function of the time. Materials and Methods: We retrospectively investigated the correlation between the RI and the graft survival (GS) and the overall survival (OS) after transplantation. We evaluated 268 patients transplanted between 2003 and 2011, the mean followup was 73 months (12-136). The RI was evaluated at 8 days, 6 months, 1 year and 3 years. The ROC analysis was used to calculate the predictive value of RI and the Kaplan Mayer curves was used to evaluated the OS and PS. Results: The ROC analysis, correlated to the GS, identified a value of RI equal to 0.75 as a cut-off. All patients was stratified according to the RI at 8 days (RI ≤ 0,75: 212 vs RI > 0.75: 56), at 6 months (RI ≤ 0.75: 237 vs RI > 0.75: 31), at 1 year (RI ≤ 0.75: 229 vs RI > 0.75: 39) and at 3 years (RI ≤ 0.75: 224 vs RI > 0.75: 44). The RI showed statistically significant differences between the two groups in favor of those who had an RI ≤ 0.75 only at 8 days and at 6 moths (p = 0.0078 and p = 0.02 to 8 days to 6 months) on the GS. On the contrary, we observed that the RI estimated at 1 year and 3 years has not correlated with the GS. The same RI cut-off was correlate with PS after transplantation. We observed that there are no correlations between the RI and OS. Conclusions: The RI proved to be a good prognostic factor on survival organ when it was evaluated in the first months of follow- up after transplantation. This parameter does not appear, however, correlate with OS of the transplanted subject.