CELL-MEDIATED CYTOTOXICITY - A PREDICTOR OF CHRONIC REJECTION IN PEDIATRIC HLA HAPLOIDENTICAL RENAL-TRANSPLANTS

Background. Recipient antidonor cytotoxic T-cell activity has been ass ociated with graft loss and acute rejection in renal allograft recipie nts, The role of immunologic mechanisms in the development of chronic graft rejection is controversial, We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 t o 1995 to assess whether cell-mediated cytotoxicity, determined in vit ro and measured before transplantation, was predictive of chronic reje ction. Methods. Eighty-three patients were studied retrospectively. Fi fty-seven patients with one haplotype-matched renal transplants from l iving related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejec tion, and graft failure. Acute rejection was defined by the decision t o treat. Chronic rejection was defined by histology and/or the absolut e serum creatinine value using an increasing serum creatinine level >1 .0 mg/dl for children less than 3, a creatinine level > 1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg /dl for children above 10 years of age. Return to dialysis or retransp lantation was considered graft failure. Results. Of the 57 haploidenti cal patients, there were 33 males and 24 females, The mean age at tran splant was 11.1 years (SD=6.7). Twelve patients developed chronic reje ction, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058), Controlling for age and se x, Cox's proportional hazards model revealed that CML level was predic tive of time to chronic rejection (P<0.01) but not acute rejection (P= 0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HL A-identical kidneys from their siblings. There were no episodes of chr onic rejection after 5 years. Two patients with high CML levels had ep isodes of acute rejection; both patients responded to treatment. Concl usion. Our data demonstrate an association between pretransplant cell- mediated cytotoxicity and the occurrence of chronic rejection in livin g related one-haploidentical renal transplants in pediatric patients.