Background: In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial.
Methods: For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B.
Results: With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9±4.2 vs. 83.6±6.9 and 79.8±5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group.
Conclusions: Long-term results clearly indicate inferior clinical outcomes in group B.
1 Miami Transplant Institute, Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, and Jackson Memorial Hospital, Miami, FL.
2 Miami Transplant Institute, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, and Jackson Memorial Hospital, Miami, FL.
3 Address correspondence to: Gaetano Ciancio, M.D., Miami Transplant Institute, Jackson Memorial Hospital and The Department of Surgery, University of Miami Miller School of Medicine, P.O. Box 012440 (R-440), Miami, FL 33101.
The authors declare no funding or conflicts of interest.
Clinical Trial Registration at Clinical Trials.gov (ID:NCT00685061 and NCT00681343)
G.C. participated in the research design, performance of the research, data analysis, and writing of the article. J.J.G. participated in the research design, performance of the research, data analysis, and writing of the article. G.G., J.S., L.C., A.M., D.R., W.K., and L.T. participated in the research design and performance of the research. L.T, S.F., L.H., and R.V. participated in the performance of the research. G.W.B. participated in the research design, performance of the research, data analysis, and writing of the article.
Received 19 August 2013. Revision requested 19 September 2013.
Accepted 6 November 2013.