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Outcome of Living Kidney Transplant: Pediatric in Comparison to Adults
Outcome of Living Kidney Transplant: Pediatric in Comparison to Adults M. Torkaman, Z. Khalili-Matin-Zadeh, M. Azizabadi-Farahani, M. Moghani-Lankarani, S. Assari, V. Pourfarziani, S.H. Saadat, Z. Kavehmanesh, and S. Afshar-Payman ABSTRACT Background. Renal transplantation is the most optimal way to manage children with end-stage renal disease. Despite its benefits, pediatric renal transplantation is a challenge for several transplantation centers in terms of achieving a satisfactory outcome. We sought to compare the long-term outcome of pediatric versus adult recipients who underwent renal transplantation. Method. We examined, 2631 recipients of a first kidney from a living donor between 1982 and 2002. The two groups were matched for immunosuppressive therapy and number of HLA mismatches. The patients were divided into a pediatric (n ⫽ 301; age ⱕ 18 years) and an adult group (n ⫽ 2330; age ⬎ 18 years) to compare 5-year patient and graft survivals. Results. The mean ages of the pediatric and adult groups were 40 ⫾ 13 and 14 ⫾ 13 years, respectively. The 5-year graft survival was lower among the pediatric versus the adult group (56% vs 68%; P ⫽ .015) with no difference in patient survival (88% vs 86%; P ⬎ .05). Conclusion. The poorer graft survival in pediatric transplantation may be due to the nature of pediatric transplantation, in terms of inconsistent adherence to medication regimens, worse side effects of medications, higher rate of graft rejection due to recurrent disease, and more intense immunoreactivity of children.
K
IDNEY TRANSPLANTATION is the treatment of choice for children with end-stage renal disease (ESRD), because it not only provides freedom from dialysis, but also the best opportunity for normal growth, development,1 and lifestyle.2 It is also cost effective, improves school performance, and reduces family problems.3 Successful transplantation may be the only way to make these children productive individuals in society.4 Beside these benefits, children transplantation in has not achieved the developments that have been made in adult transplantation. Data in this field are also limited, perhaps due to the poorer outcomes of pediatric transplantation that decrease the interest of transplantation centers and also the fact that a large number of these patients fail to follow-up, by moving away from their primary transplantation centers, when they mature into young adults.5 Although Otukesh et al6 described the long-term outcome of pediatric renal transplanted patients in one Iranian transplantation center, there is no published comparison regarding the outcomes in pediatric versus adult patients in our
country. We sought to investigate updated pediatric transplantation survival in the two active transplantation centers in Tehran. METHODS This retrospective study of 2631 Iranian kidney recipients who had undergone their first kidney transplantations between 1982 and 2002 divided the patients into a pediatric (n ⫽ 301, age ⱕ 18 years) versus an adult group (n ⫽ 2330, age ⬎ 18 years). Demographic From the Nephrology/Urology Research Center (NURC), Baqiyatallah Medical Sciences University (M.T., Z.K.-M.-Z., V.P., S.H.S., Z.K., S.A.-P.) and the Clinical Research Unit, Baqiyatallah Medical Sciences University (M.A.-F., M.M.-L., S.A.), Tehran, Iran. Fully supported and funded by Baqiyatallah Medical Sciences University. Address reprint requests to Mohammad Torkaman, Baqiyatallah University of Medical Sciences, Vanak Square, Mollasadra Ave. 19945-587, PO Box 14155-6437 - Postal code: 1435915371 Tehran, Iran. E-mail: torkaman.mohammad@ gmail.com
0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.03.090
© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
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Transplantation Proceedings, 39, 1088 –1090 (2007)
PEDIATRIC VS ADULT TRANSPLANTATION data, source of kidney, mode of transplantation, cause of ESRD, survival death, with death with a functioning graft considered as an event were collected from the patient charts. Data analysis was preformed using SPSS for Windows 13. Graft and patient survivals were assessed by Kaplan–Meier. Graft and patient survivals were compared using the log-rank test. Means, standard deviations (SD), and confidence intervals (CI) for patient and graft survivals were compared between the two groups. P values less than .05 were considered significant.
RESULTS
Among the pediatric and adult patients, 173 (57.5%) and 1498 (64.3%) were male subjects (P ⫽ .02). Mean ⫾ SD (range) age of pediatric and adult groups were 14 ⫾ 3 (range, 6 to 18) and 40 ⫾ 14 years (range, 19 to 84). No difference in graft survival rates between 5– 6 HLA-A, -B, and -DR mismatches was observed between the two groups (96 [32%] vs. 699 [30%]; P ⫽ .501). There was also no significant difference in the immunosuppressive protocol. Although all transplants were donated from living donors, the frequency of living-related donors was higher in the pediatric group (36 [12%] vs. 116 [5%]; P ⫽ .001). There was a similar pattern for the frequency of preemptively transplantation (93 [31%] vs. 186 [8%]; P ⫽ .001). The 5-year graft survivals were 56% and 68%, respectively, for pediatric and adult groups (P ⫽ .0015). The 5-year patient survivals were 88% and 86%, respectively, for pediatric and adult groups (P ⬎ .05). Mean graft survival for pediatric and adult groups was 68 ⫾ 3 months (95% CI, 62 to 74) and 76 ⫾ 1 months (95% CI, 74 to 79; P ⫽ .015). Mean patient survival for pediatric and adult groups was 103 ⫾ 2 months (95% CI, 98 to 107) and 76 ⫾ 1 months (95% CI, 99 to 104; P ⫽ .015). DISCUSSION
More than 10% of all living renal transplantations in our two transplantation centers are performed in pediatric recipients, a proportion that is twice greater than the reported rates in the United States and Turkey.7,8 Studies comparing the outcomes of renal transplantation in adults and pediatrics are scarce. Although we reported that lower graft survival by pediatric renal transplant patients, there are also contrary reports from other countries.9 Renal transplantation has been reported to be improving, which may be due to new immunosuppressive drugs, greater medical and surgical experience, and better compliance.6 The challenges of pediatric renal transplantation include an higher incidence of rejection episodes, more difficult technique, size match problems,10 different side effect pattern of medications,3 higher rate of recurrence,11 and more intense immunoreactivity.12 There is also greater risk for posttransplant infectious complications, including lymphoproliferative disease in pediatric transplantation.13 In addition, pediatric recipients are more prone to some kinds of infection (e.g., cytomegalovirus) because they are more commonly seronegative.14
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The 5-year patient and graft survivals in our study were 88% and 56%, respectively. These rates were 74% and 67%, in a previous report in Iran6; 87% and 73% in Egypt15; 84% and 44% in South Africa16; 100% and 71% in Chile17; and 98% and 71% in Portugal.8 In India, the 5-year graft survival has been reported to be 47%.18 In all theses studies, although graft survival rates are not the same, they are unsatisfactory. The differences in pediatric graft survival may be due to disparities in quality of health care, race, etiology of ESRD, preemptive transplantation, treatment protocol, source of kidney, and several other causes.16,19 The difference in definition of pediatric groups may be another cause. There is much work to be done as pediatric renal replacement comes of age. Barriers to transplantation in children with ESRD must be overcome, and greater longevity of allografts attained. Toward this goal, our transplantation team needs to gain more experience in pediatric transplantation.
REFERENCES 1. Seki T, Koyanagi T, Chikaraishi T, et al: Clinical experience of pediatric kidney transplantation: what is the benefit? Transplant Proc 32:1822, 2000 2. Yadin O, Grimm PC, Ettenger RB: Renal transplantation in children. Pediatr Ann 20:657, 1991 3. Mehrabi A, Kashfi A, Tonshoff B, et al: Long-term results of paediatric kidney transplantation at the University of Heidelberg: a 35 year single-centre experience. Nephrol Dial Transplant 19(Suppl 4)iv69, 2004 4. Berber I, Tellioglu G, Yigit B, et al: Pediatric renal transplantation: Clinical analysis of 28 cases. Transplant Proc 38:4302006 5. Milliner DS: Pediatric renal-replacement therapy— coming of age. N Engl J Med 350:2637, 2004 6. Otukesh H, Basiri A, Simfrosh N, et al: Outcome of pediatric renal transplantation in Labfi Nejad Hospital, Tehran, Iran. Pediatr Nephrol 21:1459, 2006 7. Emiroglu R, Moray G, Sevmis S, et al: Long-term results of pediatric kidney transplantation at one center in Turkey. Transplant Proc 37:2951, 2005 8. US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients. 2003 Annual report. Available from www.optn.org. Accessed June 3, 2004 9. Parada B, Figueiredo A, Nunes P, et al: Pediatric renal transplantation: comparative study with renal transplantation in the adult population. Transplant Proc 37:2771, 2005 10. Salvatierra O Jr, Millan M, Concepcion W: Pediatric renal transplantation with considerations for successful outcomes. Semin Pediatr Surg 15:208, 2006 11. Mathew TH: Recurrence of disease following renal transplantation. Am J Kidney Dis 12:85, 1988 12. Chu SH, Chen Y, Chiang YJ, et al: Outcome of pediatric renal transplantation in a single center from Taiwan. Transplant Proc 35:163, 2003 13. Neu AM: Special issues in pediatric kidney transplantation. Adv Chronic Kidney Dis 13:62, 2006 14. Aikawa A, Hasegawa A: Pediatric kidney transplantation. Nippon Rinsho 63:1993, 2005 15. El-Husseini AA, Foda MA, Bakr MA, et al: Pediatric live-donor kidney transplantation in Mansoura Urology & Nephrology Center: a 28-year perspective. Pediatr Nephrol 21: 1464, 2006
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16. Pitcher GJ, Beale PG, Bowley DM, et al: Pediatric renal transplantation in a South African teaching hospital: a 20-year perspective. Pediatr Transplant 10:441, 2006 17. Delucchi A, Ferrario M, Varela M, et al: Pediatric renal transplantation: a single center experience over 14 years. Pediatr Transplant 10:193, 2006
18. Phadke K, Iyengar A, Karthik S, et al: Pediatric renal transplantation: the Bangalore experience. Indian Pediatr 43:44, 2006 19. Omoloja A, Stolfi A, Mitsnefes M: Racial differences in pediatric renal transplantation-24-year single center experience. J Natl Med Assoc 98:154, 2006
K
IDNEY TRANSPLANTATION is the treatment of choice for children with end-stage renal disease (ESRD), because it not only provides freedom from dialysis, but also the best opportunity for normal growth, development,1 and lifestyle.2 It is also cost effective, improves school performance, and reduces family problems.3 Successful transplantation may be the only way to make these children productive individuals in society.4 Beside these benefits, children transplantation in has not achieved the developments that have been made in adult transplantation. Data in this field are also limited, perhaps due to the poorer outcomes of pediatric transplantation that decrease the interest of transplantation centers and also the fact that a large number of these patients fail to follow-up, by moving away from their primary transplantation centers, when they mature into young adults.5 Although Otukesh et al6 described the long-term outcome of pediatric renal transplanted patients in one Iranian transplantation center, there is no published comparison regarding the outcomes in pediatric versus adult patients in our
country. We sought to investigate updated pediatric transplantation survival in the two active transplantation centers in Tehran. METHODS This retrospective study of 2631 Iranian kidney recipients who had undergone their first kidney transplantations between 1982 and 2002 divided the patients into a pediatric (n ⫽ 301, age ⱕ 18 years) versus an adult group (n ⫽ 2330, age ⬎ 18 years). Demographic From the Nephrology/Urology Research Center (NURC), Baqiyatallah Medical Sciences University (M.T., Z.K.-M.-Z., V.P., S.H.S., Z.K., S.A.-P.) and the Clinical Research Unit, Baqiyatallah Medical Sciences University (M.A.-F., M.M.-L., S.A.), Tehran, Iran. Fully supported and funded by Baqiyatallah Medical Sciences University. Address reprint requests to Mohammad Torkaman, Baqiyatallah University of Medical Sciences, Vanak Square, Mollasadra Ave. 19945-587, PO Box 14155-6437 - Postal code: 1435915371 Tehran, Iran. E-mail: torkaman.mohammad@ gmail.com
0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.03.090
© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1088
Transplantation Proceedings, 39, 1088 –1090 (2007)
PEDIATRIC VS ADULT TRANSPLANTATION data, source of kidney, mode of transplantation, cause of ESRD, survival death, with death with a functioning graft considered as an event were collected from the patient charts. Data analysis was preformed using SPSS for Windows 13. Graft and patient survivals were assessed by Kaplan–Meier. Graft and patient survivals were compared using the log-rank test. Means, standard deviations (SD), and confidence intervals (CI) for patient and graft survivals were compared between the two groups. P values less than .05 were considered significant.
RESULTS
Among the pediatric and adult patients, 173 (57.5%) and 1498 (64.3%) were male subjects (P ⫽ .02). Mean ⫾ SD (range) age of pediatric and adult groups were 14 ⫾ 3 (range, 6 to 18) and 40 ⫾ 14 years (range, 19 to 84). No difference in graft survival rates between 5– 6 HLA-A, -B, and -DR mismatches was observed between the two groups (96 [32%] vs. 699 [30%]; P ⫽ .501). There was also no significant difference in the immunosuppressive protocol. Although all transplants were donated from living donors, the frequency of living-related donors was higher in the pediatric group (36 [12%] vs. 116 [5%]; P ⫽ .001). There was a similar pattern for the frequency of preemptively transplantation (93 [31%] vs. 186 [8%]; P ⫽ .001). The 5-year graft survivals were 56% and 68%, respectively, for pediatric and adult groups (P ⫽ .0015). The 5-year patient survivals were 88% and 86%, respectively, for pediatric and adult groups (P ⬎ .05). Mean graft survival for pediatric and adult groups was 68 ⫾ 3 months (95% CI, 62 to 74) and 76 ⫾ 1 months (95% CI, 74 to 79; P ⫽ .015). Mean patient survival for pediatric and adult groups was 103 ⫾ 2 months (95% CI, 98 to 107) and 76 ⫾ 1 months (95% CI, 99 to 104; P ⫽ .015). DISCUSSION
More than 10% of all living renal transplantations in our two transplantation centers are performed in pediatric recipients, a proportion that is twice greater than the reported rates in the United States and Turkey.7,8 Studies comparing the outcomes of renal transplantation in adults and pediatrics are scarce. Although we reported that lower graft survival by pediatric renal transplant patients, there are also contrary reports from other countries.9 Renal transplantation has been reported to be improving, which may be due to new immunosuppressive drugs, greater medical and surgical experience, and better compliance.6 The challenges of pediatric renal transplantation include an higher incidence of rejection episodes, more difficult technique, size match problems,10 different side effect pattern of medications,3 higher rate of recurrence,11 and more intense immunoreactivity.12 There is also greater risk for posttransplant infectious complications, including lymphoproliferative disease in pediatric transplantation.13 In addition, pediatric recipients are more prone to some kinds of infection (e.g., cytomegalovirus) because they are more commonly seronegative.14
1089
The 5-year patient and graft survivals in our study were 88% and 56%, respectively. These rates were 74% and 67%, in a previous report in Iran6; 87% and 73% in Egypt15; 84% and 44% in South Africa16; 100% and 71% in Chile17; and 98% and 71% in Portugal.8 In India, the 5-year graft survival has been reported to be 47%.18 In all theses studies, although graft survival rates are not the same, they are unsatisfactory. The differences in pediatric graft survival may be due to disparities in quality of health care, race, etiology of ESRD, preemptive transplantation, treatment protocol, source of kidney, and several other causes.16,19 The difference in definition of pediatric groups may be another cause. There is much work to be done as pediatric renal replacement comes of age. Barriers to transplantation in children with ESRD must be overcome, and greater longevity of allografts attained. Toward this goal, our transplantation team needs to gain more experience in pediatric transplantation.
REFERENCES 1. Seki T, Koyanagi T, Chikaraishi T, et al: Clinical experience of pediatric kidney transplantation: what is the benefit? Transplant Proc 32:1822, 2000 2. Yadin O, Grimm PC, Ettenger RB: Renal transplantation in children. Pediatr Ann 20:657, 1991 3. Mehrabi A, Kashfi A, Tonshoff B, et al: Long-term results of paediatric kidney transplantation at the University of Heidelberg: a 35 year single-centre experience. Nephrol Dial Transplant 19(Suppl 4)iv69, 2004 4. Berber I, Tellioglu G, Yigit B, et al: Pediatric renal transplantation: Clinical analysis of 28 cases. Transplant Proc 38:4302006 5. Milliner DS: Pediatric renal-replacement therapy— coming of age. N Engl J Med 350:2637, 2004 6. Otukesh H, Basiri A, Simfrosh N, et al: Outcome of pediatric renal transplantation in Labfi Nejad Hospital, Tehran, Iran. Pediatr Nephrol 21:1459, 2006 7. Emiroglu R, Moray G, Sevmis S, et al: Long-term results of pediatric kidney transplantation at one center in Turkey. Transplant Proc 37:2951, 2005 8. US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients. 2003 Annual report. Available from www.optn.org. Accessed June 3, 2004 9. Parada B, Figueiredo A, Nunes P, et al: Pediatric renal transplantation: comparative study with renal transplantation in the adult population. Transplant Proc 37:2771, 2005 10. Salvatierra O Jr, Millan M, Concepcion W: Pediatric renal transplantation with considerations for successful outcomes. Semin Pediatr Surg 15:208, 2006 11. Mathew TH: Recurrence of disease following renal transplantation. Am J Kidney Dis 12:85, 1988 12. Chu SH, Chen Y, Chiang YJ, et al: Outcome of pediatric renal transplantation in a single center from Taiwan. Transplant Proc 35:163, 2003 13. Neu AM: Special issues in pediatric kidney transplantation. Adv Chronic Kidney Dis 13:62, 2006 14. Aikawa A, Hasegawa A: Pediatric kidney transplantation. Nippon Rinsho 63:1993, 2005 15. El-Husseini AA, Foda MA, Bakr MA, et al: Pediatric live-donor kidney transplantation in Mansoura Urology & Nephrology Center: a 28-year perspective. Pediatr Nephrol 21: 1464, 2006
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16. Pitcher GJ, Beale PG, Bowley DM, et al: Pediatric renal transplantation in a South African teaching hospital: a 20-year perspective. Pediatr Transplant 10:441, 2006 17. Delucchi A, Ferrario M, Varela M, et al: Pediatric renal transplantation: a single center experience over 14 years. Pediatr Transplant 10:193, 2006
18. Phadke K, Iyengar A, Karthik S, et al: Pediatric renal transplantation: the Bangalore experience. Indian Pediatr 43:44, 2006 19. Omoloja A, Stolfi A, Mitsnefes M: Racial differences in pediatric renal transplantation-24-year single center experience. J Natl Med Assoc 98:154, 2006