Conversion from azathioprina to mycophenolate mofetil in pediatric renal transplant recipients with chronic rejection

Background. Chronic rejection is the leading cause of graft failure. Both nonimmunological and immunological mechanisms contribute to this pathology. Methods. We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, serum HLA class I antigens, cytotoxic antibodies, and lymphocyte population before and after 6 months of follow-up in 22 pediatric renal transplanted patients, The immunosuppressive protocol used was: cyclosporine, azathioprine, and corticosteroids, Eight patients demonstrated chronic graft rejection (by biopsy), group I; and eight patients had no clinical evidence of chronic and/or acute rejection, group II. Substitution of mycophenolate mofetil (MMF) (600 mg/m(2) bid for azathioprine was done in patients of groups I and II, Another six patients with chronic rejection, did not receive MMF, group III. Results. Creatinine clearance increased in group I (44+/-5 vs. 51.1+/-6 ml/min/1.73 m(2), P<0.03) but it decreased in group III (30+/-3 vs. 25+/-2, P<0.01), Urinary protein excretion decreased only in group I (0.3+/-0.03 to 0.06+/-0.03 g/24 hr, P<0.03). During MMF therapy antidonor mixed lymphocyte culture decreased 62 and 70% (P<0.05) in group I and II. Cell-mediated lympholysis against lymphocyte of the donor decreased 65% (P<0.05) in group I. Cell-mediated lympholysis toward control cells decreased 54% (P<0.01) in group II. Serum HLA class I antigens, only decreased from 0.7+/-0.1 to 0.5+/-0.1 mu l/ml, P<0.05, in group I. CD19(+) decreased from 7.9+/-1.1 to 5.6+/-0.8%, P<0.05, and 7.8+/-1.2 to 5.5+/-0.9%, P<0.05, in groups I and II, respectively. CD16(+) increased from 5.7+/-1.1 to 8.6+/-1.3 (P<0.05) only in group I. Conclusions. Our data suggest that substituting MMF for azathioprine therapy leads to an improvement in the immunosuppression and renal function in children with on-going chronic rejection.