Modeling of isolated kidney perfusion systems in transplantation ischemic tolerance

Abstract

Kidney transplantation is considered the best treatment for patients with end stage renal disease. Ischemia-reperfusion injury (IRI) is an evitable event after deceased donor transplantation and influences short term and long-term graft outcome. After kidney transplantation, the main consequences are DGF (delayed graft function), acute and chronic graft rejection and chronic graft dysfunction. The better understanding of IRI mechanisms will help to find further improvements in donated organ survival. Almost 30 % of DGF following kidney transplantation is owed to IRI. Caspases, the classical effector enzymes of apoptosis, are able to induce inflammation following IRI, which is one of the most important non-specific and nonimmunologic factor affecting not only DGF but also late allograft dysfunction. Transplantation of an ischemic organ can lead to distant organs’ dysfunction. Several mediators are released into systemic circulation during IRI and these can be disadvantageous at distant tissues and organs (native kidneys, liver, lungs and heart). The released mediators can improve permeability of capillaries and more cytokines will secreted, like TNF-alpha, IL-1 and IL-6, which cause severe cell response and it can easily end in cell necrosis or apoptosis. Transplanted kidneys are damaged organs and drugs can be used either alone or in combination to modify the effects of ischemia and reperfusion besides perfusion solutions and perfusion methods. Further investigations are required to eliminate the effects of IRI during kidney transplantation.