SP673RENAL TRANSPLANT ISCHEMIA−REPERFUSION INJURY CORRECTION WITH CYTOKINES ADSORPTION. EARLY AND LONG−TERM RESULTS

Abstract

Introduction and Aims: Cellular metabolism inadequacy in terms of hypoxia upon organ conservation leads to nephron injury. Further reperfusion in case of microvascular dysfunction exacerbates cellular injury. Cytokines play the leading role in pathogenesis of renal transplant ischemia/reperfusion injury. Effective and pathogenetically grounded therapy can substantially minimized injury severity and improve transplant function, especially of those received from expanded criteria donors. There is a method of concentration of circulating cytokines and adhesion factors decrease with the combined plasma filtration and adsorption. Its efficiency has been proved in sepsis treatment. This method was used for ischemia/reperfusion injury management for the first time. Purpose: to assess efficiency of CPFA for renal transplant ischemia/reperfusion injury severity management. To assess impact of the method on long‐term outcomes of renal transplantation with transplants received from suboptimal donors (expanded criteria donors). Methods: We conducted a prospective randomized clinical trial. We applied coupled plasma filtration and adsorption (CPFA) in 33 patients of study group. After the operation each patient had one such procedure (procedure duration 8‐10 hours). In the control group there were 33 patients who received paired transplants. All 66 transplants were received from expanded criteria donors. We investigated the cytokines serum concentrations (TNF, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70) before transplantation, after reperfusion, 4, 8, 12, 24 hours after reperfusion, and 5 days after transplantation. We also investigated transplant function parameters (glomerular filtration rate ‐ GFR, serum creatinine, daily proteinuria) 3, 6, and 12 months after transplantation. Repeated measures ANOVA with a posteriori Tukey and Fisher tests was used for statistical analysis. Results: Ischemia/reperfusion is followed by a significant release of cytokines into blood that was observed in patients of control group. In addition to this, maximum peak was recorded 4‐6 hours after reperfusion. Moreover, a significant relation with conservation duration and thermal ischemia was observed. In patients of the study group cytokine concentration remained stable after CPFA. Even 5 days after transplantation cytokine concentration was significantly lower than in control group. In patients of the main group transplant function improvement was observed: a higher rate of diuresis and GFR, blood creatinine improvement, microcirculation improvement (less resistive index). CPFA has no effect on tacrolimus blood concentration. 3 months after transplantation patients of the main group had a significantly lower level of daily proteinuria (p>;0.001); 6 months ‐ higher GFR (p=0.02) and lower daily proteinuria (p=0.02). 1 year after transplantation patients of the main group had lower creatinine plasma level (p=0.001), higher GFR (p=0.001), daily proteinuria 2.5 times lower (p=0.001) versus patients of control group. Conclusions: However, we believe that the selective removal of cytokines in the early postoperative period after kidney transplantation is an effective and necessary procedure and it may reduce the ischemia / reperfusion injury severity and improve outcomes of renal transplantation with transplants received from expanded criteria donors. This procedure is safe and highly efficient. The study assessing long‐term outcomes is in progress.