Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction.

Control of Herpesvirus Infection in Organ Transplant Recipients

The most important causes of infectious disease morbidity and mortality in organ transplant recipients are the herpesviruses, particularly cytomegalovirus (CMV) and Epstein-Barrvirus (EBV). Because of their properties of latency, cell association, and potential oncogenicity, they are particularly well suited to causing disease in the transplant patient. Antilymphocyte antibody therapies are potent reactivators of these viruses, and cyclosporine, by inhibiting the critical host defense (virus specific cytotoxic T cells) in a dose-dependent fashion, amplifies the extent and effects of the viral replication. This in turn is translated into clinical disease: fever; pneumonia; gastrointestinal ulcerations; broad-based suppression of host defences leading to opportunistic superinfection and, perhaps, allograft injury in the case of CMV; and B cell lymphoproliferative disease in the case of EBV. New approaches to controlling these viruses in which pre-emptive therapy is linked to immunosuppressive therapy, and new diagnostic techniques for viral monitoring, hold promise for limiting clinical disease due to these viruses.

Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement

Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.