Newer immunosuppressants in renal transplantation

Ever since the beginning of renal transplantation as a mode of renal replacement therapy, there has been paradigm shift in the management protocols. Renal transplantation always poses challenge to the nephrologists because of the inherent hurdles to counter the recipient's immunity. Many drugs established as efficacious in indications such as oncology (e.g., rituximab and alemtuzumab) or autoimmunity (e.g., alefacept and efalizumab) are now being proposed for use in transplantation. Their use for conditions such as antibody-mediated rejection (AMR), desensitization, induction, or maintenance therapy has been recently proved. The last several decades have seen a substantial decrease in the prevalence of acute allograft rejection in kidney-transplant recipients, while equivalent improvements in the long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include the ease of use, improved side effect profiles, and reduced nephrotoxicity in addition to the more traditional goal of improved short-term outcomes.A number of novel drugs are currently under investigation in phase I, II, or III clinical trials primarily to replace the nephrotoxic but highly effective calcineurin inhibitors (CNIs). ISA247 (voclosporine) is a cyclosporine analog with reduced nephrotoxicity in phase III study. AEB071 (sotrastaurin), a protein kinase C inhibitor, and CP-690550, a JAK3 inhibitor, are small molecules in phase II studies. Belatacept is a humanized antibody that inhibits T-cell co-stimulation and has shown encouraging results in multiple phase II and III trials. Alefacept and efaluzimab are humanized antibodies that inhibit T-cell adhesion and are in phase I and II clinical trials.