Deceased-donor kidney transplantation: improvement in long-term survival

David Serur 1 2 Stuart Saal 1 2 John Wang 1 2 John Sullivan 1 2 Roxana Bologa 1 2 Choli Hartono 1 2 Darshana Dadhania 1 2 Jun Lee 1 2 Linda M. Gerber 3 Michael Goldstein 0 Sandip Kapur 0 William Stubenbord 0 Rimma Belenkaya 2 Marina Marin 2 Surya Seshan 4 Quanhong Ni 3 Daniel Levine 2 Thomas Parker 2 Kurt Stenzel 1 2 Barry Smith 0 2 Robert Riggio 1 2 Jhoong Cheigh 1 2 0 Department of Surgery, New York-Presbyterian Hospital/Weill Cornell Medical Center , New York, NY, USA 1 Department of Medicine, New York-Presbyterian Hospital/ Weill Cornell Medical Center , New York, NY, USA 2 Division of Transplantation, The Rogosin Institute , New York, NY, USA 3 Department of Public Health, Weill Cornell Medical College , New York, NY, USA 4 Department of Pathology, New York-Presbyterian Hospital/Weill Cornell Medical Center , New York, NY, USA Background. Despite marked improvement in short-term renal allograft survival rates (GSR) in recent years, improvement in long-term GSR remained elusive. Methods. We analysed the kidney transplant experience at our centre accrued over four decades to evaluate how short-term and long-term GSR had changed and to identify risk factors affecting graft survival. The study included 1476 adult recipients of a deceased-donor kidney transplant who were transplanted between 1963 and 2006 and who had received one of five distinct immunosuppressive protocols. Results. Five-year actual GSR steadily improved over the years as immunosuppressive therapy evolved (22-86%, P < 0.001) in spite of an increasing trend in the transplantation of higher-risk donor-recipient pairings. For those whose grafts functioned for the first year, subsequent 4-year GSR (5-year conditional GSR) also improved significantly (63-92%, P < 0.001). Acute rejection and delayed graft function (DGF) were the most significant risk factors for actual graft survival, while acute rejection was the only significant risk factor for conditional GSR. Use of kidneys from expanded-criteria donors (ECD) was not a risk factor, compared to the use of standard-criteria donor kidneys for either 5-year actual or conditional GSR. There was an impressive decline in the incidence of acute rejection events (77.4-5.8%, P < 0.001). While the DGF rate had decreased, it still remained high (68.7-38.5%, P < 0.001). Conclusions. We found a significant improvement in both short-term and long-term GSR of deceased-donor kidney transplants over the last four decades. These improvements are most likely related to the decreased incidence of acute rejection episodes. Minimizing acute rejection events and preventing DGF could result in further improvement in the GSR. Our experience in the judicious use of ECD kidneys suggests that this source of kidneys could be expanded further. Introduction The management of kidney transplantation has evolved over more than half a century. Published literature has documented the remarkable progress made in surgical techniques, types and use of immunosuppression, diagnosis and management of complications and patient and graft outcomes [1]. Despite these advances, improvement in long-term graft survival after the first year of successful transplant has not been consistently found. Hariharan et al. [2] reported a substantial increase in both short-term and long-term graft survival between 1988 and 1996 in the United States and attributed this improvement to a significant decrease in the incidence of acute rejection. On the other hand, Meier-Kriesche et al. [3] reported a lack of improvement in long-term renal allograft survival despite a marked decrease in the acute rejection rate between 1988 and 1995. Recent analyses of large databases revealed no substantive evidence for finding improved long-term renal allograft survival in the last decade [4,5]. It is also unclear why there has been no improvement in long-term graft survival given the availability of more effective immunosuppressive medications, better control of acute transplant rejection and improved antimicrobial prophylaxis. The kidney transplant programme at our centre began in 1963 and five distinct immunosuppressive protocols were sequentially introduced from that time to the present. We reviewed our kidney transplant experience over the past four decades to study what effect evolving immunosuppressive therapies had on short-term and long-term kidney transplant outcomes. In addition, we attempted to identify risk factors that had a significant adverse impact on shortterm and long-term graft survival. Materials and methods We used a single-centre, nonrandomized, retrospective study designed to evaluate outcomes in kidney transplant recipients treated with one of five different immunosuppressive protocols under the coordinated effort of a multidisciplinary team over four decades. The study included 1476 adult kidney transplant patients who had received a kidney from deceased donors between 1963 and 2006 at The New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY. It excluded paediatric patients, recipients of a living-donor kidney and those who had received dual kidneys or a simultaneous kidney pancreas transplant. Demographic and other pertinent information are shown in Table 1. Between 1963 and 2006, we utilized five distinct immunosuppressive protocols: prednisone and azathioprine (Imuran, Prometheus Lab., San Diego, CA) between 1963 and 1983 (Protocol 1); prednisone, azathioprine and cyclosporine (Neoral, Novartis, East Hanover, NJ) between 1983 and 1994 (Protocol 2); prednisone, cyclosporine and mycophenolate mofetil (CellCept, Roche, Nutley, NJ) between 1995 and 1997 (Protocol 3); prednisone, mycophenolate mofetil and tacrolimus (Prograf, Astellas, Deerfield, IL) between 1997 and 2006 (Protocol 4); antibody induction with rabbit anti-thymocyte globulin (Thymoglobulin, Genzyme, Cambridge, MA), tacrolimus, mycophenolate mofetil and a steroid-sparing protocol (intravenous methylprednisone for Postoperative Days 04) between 2001 and 2006 (Protocol 5). In addition to these basic protocols, various other adjunctive medications and procedures were utilized at different times to prevent and/or treat acute rejection. For example, local irradiation, anti-lymphocyte globulin, human gamma globulin and donor-specific blood transfusion were also utilized along with Protocol 1. Similarly, Orthoclone OKT3, basiliximab, daclizumab, anti-thymocyte globulin, human gamma globulin, plasmapheresis and donor-specific blood transfusions with Protocols 24 and sirolimus, rituximab and alemtuzumab with Protocol 5. The presence of overlapping time periods for protocols was usually caused by a need to use the prior protocol due to medical necessity, such as the need for corticosteroid therapy or by the presence of hypersensitivity to a drug used in the current protocol. In addition, there had been considerable advancement in surgical and organ preservation techniques, use of antimicrobial prophylaxis, as well as overall (...truncated)