The Canadian Journal of Urology; 6(5); October 1999 Accepted for pu blication May 2000 Address correspondence to Dr. Philip Belitsky, MD, Professor of Urolog y, Dept. of Urology, Faculty of Medicine, Dalhousie University, Rm.294 5 South, Victoria Building, 127 8 T ow er Road, H alifax, N ova Sc otia B3H 2Y9 T el: (902) 473-5469 Fax: (902) 473-5850 Introduction Renal transplantation is the preferred treatment for virtually all causes of end-stage renal disease (ESRD). Since the description of the first renal transplan ts in non- imm unosup pressed patients by Hum e, 5 0 years ago, we have been witness to remarkable improvements in clinical outcomes. 1 Graft survival has increased and episod es of acute reje ction have decreased. We have a better understanding of the complex immunological processes involved in transplantations tha t have aid ed the development of immunosuppression regimes meant to target specific T-cell interactions and to interrupt distinct bi ochemic al pathw ays. There has bee n a p aradigm shif t fro m broad nonspeci fi c imm un osup pression to n ew combinations aimed at lowering overall doses and maximizing outcomes, while minimizing toxicities. Modern immunosuppression has catapulted t h e Progr ess i n renal t ranspl ant at io n Chr istop her G. French, MD, Ph ili p B elitsky, MD, J osep h G. Lawen Depa rtm ent of Urology , QEII Hea lth Sc ience Center, Dalhou sie University, Ha lifax, Nov a Sc otia FRENC H CG, BELITS KY P , LAWEN JG. Pro gr ess in Renal Transplantation. The Canadian Journal of Urology. 2000;7(3):000-000. Purpose: The improvements in renal transplantation over the last 10 years have been one of the great success st orie s in medicine. We have reviewed these su cce sses with a focus on the following: changes in demographics of donors and recipients in Canada, the benefits of new immunosuppressive regimes and the efforts to minimize their toxicity and finally, our un dersta ndin g of mea sures to circumvent chronic rejection. Materials and methods: A review of current transplantation literature was performed and pertinentdata prese nt ed. A s well, information from the Canadian Organ Replacement Register was selected to provide an overview of changes in renal transplantation in Canada. Results: Despite the stable rate of transplantation in Canada , t he num be r of new patient s start ing dialysis ea ch year roughly equals the entire national renal transplantwaitin g list. These patients are olde r a nd have more complex co-morbidities, mandating prudent use ofimmunos uppressi on so as to minim ize toxic ity. St anda rdtriple therapy consists of a calcineurin inhibitor, an ant imet ab olite and co rti co st ero ids. A nt ibo dy therapy is indicated in sensitized recipients and newer monoclonal hum anized anti bo dies offe r less toxicit y. N onspec ific therapies a re le ss favorable , du e to un wan ted side effec ts . We can now identify subsets of patients who are mostlikely to be nefit from spe cific therapy. N ewer non- nephrotoxic agents hold promise for future regimens. However, a paucity of large, multicenter, randomizedtrials, tested against standard protocols, limits theircurrent in dic atio ns. M any immu nolo gic and non- immunologic factors influence the outcome of renal transplant atio n and play a role in the develo pment of a cute and chronic rejection. Conclusions: The challenges of renal transplantation over the next 10 years are: 1) in the development of specific therapies that can be altered according to patientco-morbidities and other factors influencing outcome; 2) minimizing toxicity; 3) preventing chronic rejection; and 4) impro vin g our n atio nal or gan donatio n netw ork . K e y Words:transplantation, kidney, immunosuppression
