Effect of Mycophenolate Mofetil on Long-Term Outcomes in African American Renal Transplant Recipients HERWIG-ULF MEIER-KRIESCHE, AKINLOLU O. OJO, ALAN B. LEICHTMAN, JEFFREY D. PUNCH, JULIE A. HANSON, DIANE M. CIBRIK, and BRUCE KAPLAN Departments of Medicine and Surgery, University of Michigan, Ann Arbor, Michigan. Abstract. African American renal transplant recipients have poorer graft survival. A study using the United States Renal Data Registry documented an improvement in graft survival for patients who took mycophenolate mofetil (MMF) com- pared with azathioprine (AZA). This analysis did not address the impact of MMF on African American renal transplant recipients. The present study aimed to quantify potential ben- eficial effects of MMF therapy on long-term renal allograft survival in African Americans. With the use of the United States Renal Data Registry, all adult Caucasian and African American patients who had received a primary renal transplant between 1988 and 1997 were analyzed by Kaplan-Meier anal- ysis and Cox proportional hazard models. Primary study end points were death with a functioning graft and graft failure censored for death. A total of 57,926 patients were studied. For African Americans, 3-yr patient survival was 96.3 versus 93.2% (P  0.001) for MMF and AZA, respectively. Three-yr death-censored graft survival for African Americans was 85.8 versus 75.1% (P  0.001) for MMF and AZA, respectively. For Caucasians, 3-yr patient survival was 97.3 versus 93.2% for MMF and AZA, respectively. Three-yr death-censored graft survival for Caucasians was 90.1 versus 86.4% (P  0.001) for MMF and AZA, respectively. By multivariate anal- ysis, MMF was associated with a significant reduction in the relative risk for all study end points in African Americans. MMF therapy is associated with both improved patient and death-censored graft survival in African American renal trans- plant recipients. This benefit is comparable to the benefit of MMF in Caucasian renal transplant recipients. The efficacy of mycophenolate mofetil (MMF) in decreasing acute rejection episodes in renal transplant recipients has been well documented (1–3). Long-term improvements in graft sur- vival with MMF therapy have been more difficult to demon- strate. The two prospective Phase III studies of MMF were not statistically powered to demonstrate a significant long-term impact of MMF therapy on graft survival (1,2). Despite this, one of these studies was able to demonstrate a significant improvement in 3-yr death-censored graft survival for patients in the 2 g/d MMF study arm versus control patients (3). A recent analysis of the United States Renal Data Registry doc- umented a significant decrease in the risk of development of chronic allograft failure for patients who were receiving MMF as compared with patients who were receiving azathioprine (AZA) therapy (4). This analysis also found an improvement in 3-yr death-censored graft survival for patients receiving MMF therapy. These analyses were inclusive of the entire renal transplant population and did not initially address the effect of MMF on higher risk groups, such as African American renal transplant recipients. A post hoc racial subgroup analysis of the Phase III United States study indicated that the effect of MMF in decreasing acute rejection was not as great in African American renal transplant recipients as opposed to other ethnic groups (5). In fact, this analysis indicated that higher doses of MMF were required in African American patients to achieve a comparable reduction in acute rejection episodes. African American renal transplant recipients have been shown to be at increased risk for both acute rejection and chronic allograft failure (5–10). Newer immunosuppressive agents, e.g., tacrolimus, sirolimus, and MMF, have demon- strated some beneficial effects in regard to acute rejection in African Americans (11–13), but not of the magnitude seen in Caucasian patients. More important, no study to date has documented a beneficial effect of any of these newer agents on long-term outcomes for African American renal transplant recipients. Much of the difficulty in documenting an effect on long- term outcome may be a statistical power issue rather than a lack of effect. The relatively small numbers of African Amer- ican patients enrolled in the Phase III clinical studies may preclude the ability to detect small but meaningful beneficial effects on long-term patient and graft survival. Analyses that use a larger study group with longer follow-up may document significant effects on outcome that smaller clinical studies could not. To address this issue, we analyzed the U.S. Scientific Renal Transplant Registry data, specifically addressing the long-term effects of MMF on death-censored graft survival as well as Received March 10, 2000. Accepted April 25, 2000. Correspondence to Dr. Bruce Kaplan, University of Michigan Medical Center, Department of Internal Medicine, 3914 Taubman Center, Box 0364, Ann Arbor, MI 48109-0364. Phone: 734-936-5645; Fax: 734-936-9621; E-mail: brkaplan@umich.edu 1046-6673/1112-2366 Journal of the American Society of Nephrology Copyright © 2000 by the American Society of Nephrology J Am Soc Nephrol 11: 2366 –2370, 2000