Mycophenolate mofetil in pediatric renal transplantation: non-induction vs. induction with basiliximab.

North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reports have shown anti-T cell antibody, OKT3, to be deleterious in pediatric renal transplant recipients treated with mycophenolate mofetil (MMF). Unlike OKT3, basiliximab is a chimeric monoclonal antibody to the alpha subunit of the interleukin-2 receptor on activated T-lymphocytes. We sought to examine the outcome of MMF with or without basiliximab induction therapy in pediatric renal transplantation. Between January 1998, and June 2001, 49 pediatric renal transplants were performed at our center and 41 met the criteria for this study. We retrospectively analyzed the records of 25 patients who received MMF, Prednisone, CSA or TAC, alone (group I) and 16 patients who received MMF, CSA or TAC, and Prednisone in combination with basiliximab (group II). The two groups were similar with respect to recipient or donor age, gender, ethnicity, donor source (LD vs. CAD), cold ischemia time, and primary diagnosis. The basiliximab group had a shorter follow up period because of its more recent addition to our pediatric immunosuppression protocol, 12.9 +/- 5.9 months vs. 35.5 +/- 7.2 months for group I (p < 0.0001). At 6 months, the acute rejection rate was 16% (group I) compared with 25% (group II) (p = 0.689). The patient and graft survival at 6 and 12 months were 100% respectively for both groups. Basiliximab was well tolerated without significant adverse events. At 6 months, there was no significant difference between the groups in the incidence of urinary tract infection or cytomegalovirus infection. These data suggest that in the short-term, MMF with or without basiliximab induction therapy appears to yield excellent and statistically similar outcomes. However, further controlled studies are necessary to verify these findings as well as to define the role of basiliximab in MMF-treated pediatric renal transplant recipients.

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation.

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation.