Immunosuppressive drugs and renal transplantation

Abstract

Although the use of new immunosuppressive drugs, and their combination have drastically reduced the incidence of acute rejections, the graft survival is unchanged in the last ten years. The immunosuppressive drugs can be divided in four classes, according to their different site of molecular action: proliferative signal inhibitors, amplification signal inhibitors; STATs inhibitors, DNA synthesis inhibitors. Steroids act on immune system through several mechanisms. Azathioprine is an anti-metabolite that inhibits de-novo synthesis of purins, acting on S-phase of cellular cycle. Mycophenolate-Mofetil (MMF) is also an anti-metabolite, purine synthesis inhibitor that, differently from azathioprine, acts specifically on IMPDH (Inositolmonophosphate-dehydrogenasis) through a non-competitive mechanism. Calcineurin inhibitors (cyclosporin and tacrolimus) act on amplification of intracellular signal. The most important therapeutic side-effect of calcineurin inhibitors is the nephrotoxicity. Other inhibitor agents of the amplification signal are monoclonal antibodies anti-á chain of IL-2 (CD25). Another drug used in the last years, is sirolimus (SRL) or rapamycine, an immunosuppressive agent that act, through the inhibition of T lymphocyte activation.