Long-Term Follow-Up of Renal Transplantation in Children: A Dutch Cohort Study Jaap W. Groothoff, 1,6 Karlien Cransberg, 2 Martin Offringa, 3 Nicole J. van de Kar, 4 Marc R. Lilien, 5 Jean Claude Davin, 1 and Hugo S. A. Heymans 1 Background. Few data exist on long-term morbidity, overall survival, and graft survival of pediatric renal transplantation. Methods. The authors performed a long-term cohort study in all Dutch patients, born before 1979, with onset of end-stage renal disease (ESRD) between 1972 and 1992 at age 0 to 15 years. Data on graft survival and determinants of outcome were obtained by reviewing all medical charts. The health status was assessed by cross-sectional examination of surviving patients. Results. Three hundred ninety-seven transplantations were performed in 231 of all 249 patients, of whom 25 died with a functioning graft. Cardiovascular disease was the most prominent cause of death. Graft survival estimates for all transplantations were 59.2%, 45.3%, 35.4%, and 30.3% at 5, 10, 15, and 20 years, respectively. In compar- ison with azathioprine, cyclosporine as the immunosuppressant was associated with increased graft survival in retransplantations but not in first transplantations. Cross-sectional examination was performed on 110 patients. In 44 patients, the most recent graft survival exceeded 15 years. Co-morbidity was found in 40% of all patients; motor, hearing, or visual disabilities were found in 19%. Bone disease, headaches, itching, and tremors were the most reported disabling problems. Cyclosporine use was associated with hypertension and a history of epilepsy. Compared with all age-matched Dutch inhabitants, the educational attainment was low, and unemployment and parental dependency were high. Conclusions. The authors’ results emphasize the need for reducing cardiovascular disease and metabolic bone disease in pediatric ESRD, a policy toward less toxic antirejection therapy, a more strict treatment of hypertension, and more attention for schooling and social development toward independence. (Transplantation 2004;78: 453–460) O ver the past 20 years, transplantation has become routine treatment for children with end-stage renal disease. To increase the rate of graft survival, more potent immunosuppressive regimens have been introduced over the past decade. However, concern has risen regarding the side effects of these new immunosuppressive drugs. In the discussion about the optimal immunosuppressive regimen in children undergoing transplantation, there is need for more information about the long-term effects of the earli- est immunosuppressive treatment with respect to graft sur- vival as well as co-morbidity. To date, only few data exist on these long-term outcomes. Our purpose was to investigate the long- term overall survival, graft survival, and morbidity and the in- troduction of cyclosporine as immunosuppressive therapy on these outcomes. For this purpose, we used data from the Late Effects of Renal Insufficiency in Children (LERIC) study, a na- tional Dutch long-term follow-up study that aimed to evaluate late physical, social, and psychological effects of renal insuffi- ciency in children. PATIENTS AND METHODS Study Design The study was designed as a cohort study and consisted of a cross-sectional part and a retrospective part. The aim of the cross-sectional study was to establish the current health status of the patients. The aim of the retrospective part of the study was to evaluate the influence of a set of predefined determinants on outcome parameters. The study covered the total period of renal replacement therapy (RRT) for each patient. The end of the study was marked by the day of last chart review for potential nonparticipants in the cross-sectional study and the day of the cross-sectional examination for participants. The medical ethi- cal committees of all participating centers approved the study. Formation of the Cohort The LERIC cohort comprises all Dutch patients who had started chronic RRT at age 0 to 15 years between 1972 and 1992 and who were born before 1979. Patients in whom renal function recovered within 4 months after commencing dial- ysis were excluded. Patients who underwent transplantation preemptively were included. Data on gender, date of birth, initiation of RRT, and date of death of all the patients who fulfilled the inclusion criteria were provided by the National Dutch Registry of patients on RRT (RENINE, Rotterdam, The Netherlands). RENINE, founded in 1985, is the Dutch source of the European Dialysis and Transplantation Associ- ation. The completeness approaches 100%, as registration is Financial support for the study was provided by the Dutch Kidney Founda- tion (Nierstichting Nederland). 1 Department of Pediatric Nephrology, Emma Children’s Hospital AMC, Amsterdam, The Netherlands. 2 Department of Pediatric Nephrology, Sophia Children’s Hospital, Rotter- dam, The Netherlands. 3 Department of Pediatric Clinical Epidemiology, Emma Children’s Hospital AMC, Amsterdam, The Netherlands. 4 Department of Pediatric Nephrology, St Radboud Hospital, Nijmegen, The Netherlands. 5 Department of Pediatric Nephrology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands. 6 Address correspondence to: Jaap W. Groothoff, M.D., Ph.D., Department of Pediatric Nephrology, Emma Children’s Hospital AMC, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: j.w.groothoff@amc.uva.nl. Received 15 January 2004. Revision requested 16 February 2004. Accepted 1 March 2004. Copyright © 2004 by Lippincott Williams & Wilkins ISSN 0041-1337/04/7803-453 DOI: 10.1097/01.TP.0000128616.02821.8B Transplantation • Volume 78, Number 3, August 15, 2004 453