Influence of Time of Rejection on Long-Term Graft Survival in Renal Transplantation

Background. The aim of this analysis was to investigate the relationship of acute rejection episodes (ARE) at different times posttransplantation with reversibility of graft dysfunction and long-term graft failure using data from the Collaborative Transplant Study database. Methods. A total of 28,867 patients receiving their graft between 1995 and 2005 from deceased donors were included in the analysis. The time from renal transplantation to first treated ARE was divided into intervals up to 3 years. Long-term graft survival and half-life rates were calculated and hazard ratios (HR) for failure were computed using multivariate Cox regression analysis. Results. Compared with patients who did not receive rejection treatment during the first posttransplant year, HR for graft survival increased to 1.35 for patients with rejection 0 to 90 days (P<0.001), 2.05 with rejection 91 to 180 days (P<0.001), and 2.74 with rejection 181 to 365 days of posttransplantion (P<0.001). First rejections occurring during the second year were associated with HR 3.35 (P<0.001) and rejections during the third year with HR 3.17 (P<0.001). In addition to the time of rejection, the degree of functional recovery after rejection treatment was found to be important for subsequent graft survival. Conclusion. The time point of occurrence and the degree of functional recovery after rejection treatment were found to significantly influence the impact of ARE on long-term graft survival, and we were able to quantify the associated risks.

[1]  P. Kuo,et al.  One‐Year Results with Extended‐Release Tacrolimus/MMF, Tacrolimus/MMF and Cyclosporine/MMF in De Novo Kidney Transplant Recipients , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[2]  J. D. de Fijter,et al.  Early versus late acute rejection episodes in renal transplantation , 2003, Transplantation.

[3]  Cees van Kooten,et al.  Chronic renal allograft rejection: pathophysiologic considerations. , 2005, Kidney international.

[4]  P. Vereerstraeten,et al.  Absence of deleterious effect on long-term kidney graft survival of rejection episodes with complete functional recovery. , 1997, Transplantation.

[5]  B. Jaques,et al.  The impact of late acute rejection after cadaveric kidney transplantation , 2001, Clinical transplantation.

[6]  S. Hariharan,et al.  Improved graft survival after renal transplantation in the United States, 1988 to 1996. , 2000, The New England journal of medicine.

[7]  S. Fuggle,et al.  An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  B. Kaplan,et al.  Why hasn't eliminating acute rejection improved graft survival? , 2007, Annual review of medicine.

[9]  A. Nagler,et al.  INCREASED IMPACT OF ACUTE REJECTION ON CHRONIC ALLOGRAFT FAILURE IN RECENT ERA , 2000, Transplantation.

[10]  Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients , 2000, Transplant international : official journal of the European Society for Organ Transplantation.

[11]  S. Cramer,et al.  International variation in histologic grading is large and persistent feedback does not improve reproducibility. , 2004, The American journal of surgical pathology.

[12]  A. Matas,et al.  Clinical determinants of multiple acute rejection episodes in kidney transplant recipients. , 2000, Transplantation.

[13]  Christopher P. Johnson,et al.  Post-transplant renal function in the first year predicts long-term kidney transplant survival. , 2002, Kidney international.

[14]  N Taub,et al.  International variation in the interpretation of renal transplant biopsies: report of the CERTPAP Project. , 2001, Kidney international.

[15]  A. Sancho Calabuig,et al.  Acute rejection and late renal transplant failure: risk factors and prognosis. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[16]  Y. Vanrenterghem Acute rejection and renal allograft outcome. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  M. Sayegh Why do we reject a graft? Role of indirect allorecognition in graft rejection. , 1999, Kidney international.

[18]  A. Matas,et al.  Features of acute rejection that increase risk for chronic rejection. , 1999, Transplantation.

[19]  J. Ladefoged,et al.  The effect of acute rejection on long‐term renal graft survival is mainly related to initial renal damage , 1998, Transplant international : official journal of the European Society for Organ Transplantation.

[20]  C. Ponticelli,et al.  Renal transplantation 2004: where do we stand today? , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  F. Cosio,et al.  Impact of acute rejection and early allograft function on renal allograft survival. , 1997, Transplantation.

[22]  B. Kasiske,et al.  Chronic renal allograft rejection: immunologic and nonimmunologic risk factors. , 1996, Kidney international.

[23]  W. D. Ray 4. Modelling Survival Data in Medical Research , 1995 .

[24]  S. Chadban,et al.  Results of an International, Randomized Trial Comparing Glucose Metabolism Disorders and Outcome with Cyclosporine Versus Tacrolimus , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[25]  T. Theruvath,et al.  Strategies to improve long-term outcomes after renal transplantation. , 2002, The New England journal of medicine.

[26]  J. Schold,et al.  Lack of Improvement in Renal Allograft Survival Despite a Marked Decrease in Acute Rejection Rates Over the Most Recent Era , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[27]  M. Nicholson,et al.  The aetiology and pathogenesis of chronic allograft nephropathy. , 2006, Transplant immunology.

[28]  W. Payne,et al.  THE IMPACT OF AN ACUTE REJECTION EPISODE ON LONG‐TERM RENAL ALLOGRAFT SURVIVAL (t1/2)1,2 , 1994, Transplantation.

[29]  J. Chapman,et al.  Chronic renal allograft dysfunction. , 2005, Journal of the American Society of Nephrology : JASN.

[30]  G. Opelz Critical evaluation of the association of acute with chronic graft rejection in kidney and heart transplant recipients. The Collaborative Transplant Study. , 1997, Transplantation proceedings.

[31]  M. Mihatsch,et al.  Why do kidney grafts fail? , 2002, Transplant international : official journal of the European Society for Organ Transplantation.

[32]  F. Cosio,et al.  Acute rejection following renal transplantation. Evidence that severity is the best predictor of subsequent graft survival time. , 1998, Clinical transplantation.

[33]  D. Leehey,et al.  Improved graft survival after renal transplantation in the United States, 1988 to 1996. , 2000, The New England journal of medicine.

[34]  S. Hariharan,et al.  Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis. , 2004, Kidney international.

[35]  G. Russ,et al.  Kidney Transplant Rejection in Australia and New Zealand: Relationships Between Rejection and Graft Outcome , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.