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Pediatric Kidney Transplantation: A Snapshot 10 Years Later
Pediatric Kidney Transplantation: A Snapshot 10 Years Later M. Ferraresso, L. Ghio, M. Raiteri, M. Belingheri, C. Beretta, V. Martina, A. Edefonti, and L. Berardinelli ABSTRACT Herein we report the outcomes of pediatric kidney recipients who underwent transplantation at least 10 years prior. A cohort of 36 patients (mean age, 26.4 ⫾ 6 years) with a mean follow-up time of 14.2 ⫾ 4 years was selected for the study. Immunosuppression consisted of cyclosporine and steroids. Actuarial patient and graft survivals 15 years after the transplantation were 97% and 86%, respectively. Only 1 patient died due to a complicated sclerosant peritonitis. Graft function was good with a mean serum creatinine of this selected cohort of 1.5 ⫾ 0.6 mg/dL. Eighteen percent were class 1, 33% class 2, and 49% chronic kidney disease. Hypertension was treated in almost 80% of the patients. The majority of patients were smaller than the average population with a final height (between 0 and ⫺2) standard deviation score (HSDS) but only 27% had a severe growth impairment (HSDS ⬎⫺2). Regarding nutritional status, fewer than 30% were overweight and only 1 patient was obese with a body mass index (BMI) ⬎30. The majority of patients, except 2 mentally retarded individuals, are or have been attending normal school and achieved full-time employment. In conclusion, long-term survivors of a kidney transplant received during childhood reached a high degree of rehabilitation despite a long period of immunosuppression.
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ENAL TRANSPLANTATION has become the preferred option for children of all ages with end-stage renal disease (ESRD). Nevertheless, reports on cohorts of children who have undergone a renal transplantation and have become adults are rare.1 Herein we report the longterm outcomes of a group of pediatric recipients who reached 10 years posttransplantation, with a particular emphasis on physical and social rehabilitation. PATIENTS AND METHODS Since 1969, 458 kidney transplantations have been performed in children and adolescents younger than 21 years of age, among whom 147 patients are regularly followed at our institution. From the database, we identified 36 patients who received a kidney transplant before September 1, 1997, and therefore would have reached at least 10 years follow-up on September 1, 2007. All patients (19 males/17 females) received a deceased donor kidney (mean age of the donor, 17.2 ⫾ 14 years). Mean age at transplantation was 12.2 ⫾ 5.7 years; all but 2 patients received a primary transplant. The immunosuppressive regimen consisted of cyclosporine and prednisone. Cyclosporine was started at 500 mg/m2 with median trough levels at 10 years posttransplantation of 125 ⫾ 70 ng/mL. Prednisone was administered on alternate days from 6 months. Among this cohort, we analyzed actuarial patient and graft survivals (Kaplan-Meier), graft function (serum creatinine and estimated creatinine clearance2, nutritional and growth status as
body mass index [BMI ⫽ weight (kg)/height (m)2] and height standard deviation score [HSDS ⫽ (observed height ⫺ expected height for age)/(standard deviation of mean height for age)].
RESULTS Patient and Graft Survivals
The mean follow-up period was 14.2 ⫾ 4 years (range, 10.6 –25.8 years). At this time, the mean age of the patients was 26.4 ⫾ 6 years. Actuarial patient and graft survivals at 15 years posttransplantation were 97% and 86%, respectively. One patient died at 11 years posttransplantation due to a complicated sclerosant encapsulating peritonitis, 3 From the Division of General Surgery and Kidney Tansplant (M.F., M.R., C.B., L.B.) and Pediatric Nephrology Unit (L.G., M.B., V.M., A.E.), Mangiagalli and Regina Elena Foundation, IRCCS, Milan, Italy. This work was supported by a grant from Associazione Bambino Nefropatico (ABN), Milan, Italy. Address reprint requests to Mariano Ferraresso, MD, PhD, Division of General Surgery and Kidney Transplant, Maggiore Hospital Policlinico, Mangiagalli and Regina Elena Foundation, IRCCS, Via F. Sforza 35, 20133 Milan, Italy. E-mail: mariano. [email protected]
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.003
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1852
Transplantation Proceedings, 40, 1852–1853 (2008)
PEDIATRIC KIDNEY TRANSPLANTATION
grafts were lost from chronic rejection and 1 from noncompliance at a median time of 10.6 years. Graft Function
During the follow-up, the mean serum creatinine was 1.5 ⫾ 0.6 mg/dL and mean creatinine clearance was 66.1 ⫾ 24 mL/min. Eighteen percent of the patients presented as class 1 chronic kidney disease; 33%, class 2; and 49%, class 3, according to National Kidney Foundation guidelines.3 Growth and BMI
Median height was ⫺1.33 HSDS; 10.4% had an HSDS ⬎0, 56.6% between 0 and ⫺2; and only 27% a severe growth impairment with an HSDS ⬍⫺2. Mean BMI was 23.4 ⫾ 3.7; 24% of the patients showed a BMI between 25 and 30, and only 1 patient was obese (BMI ⬎30).
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development of cardiovascular disease and an independent predictor of graft survival.7 Concerning nutritional status, only 1 patient was obese and fewer than 30% were overweight. Since corticosteroids play a pivotal role in promoting weight gain after transplantation, our steroid taper, which included alternate-day low dose steroids starting at 6 months posttransplantation, may explained the good results. Finally, adult height is a significant endpoint for children with renal failure. Many authors have reported a percentage of long-term pediatric recipients with severe impairment of height ranging from 20% to 40%.8,9 In our series, only 27% of patients had an HSDS below the 3rd percentile. Since both steroid therapy and graft function have a great impact on catch-up growth,10 our results may also be explained by our steroid schedule and by the good graft function of the patients. In conclusion, our results were encouraging, supporting efforts to offer transplantation as the preferred alternative for children with ESRD.
Malignancies and Hypertension
Two patients developed B-cell lymphomas at 3 and 14 years posttransplantation. One patient developed an EBVcorrelated leiomyoma at 9 years posttransplantation. All cases were managed successfully; all patients kept their grafts functioning. Median mean arterial pressure was 97.4 ⫾ 18.8 mm Hg; 78.3% of the patients had hypertension requiring medical therapy. Social Aspects
Excluding the 2 mentally retarded patients, all but 1 had high levels of educational achievement or full-time employment. Two patients were married and 1 of them had given birth to a child. DISCUSSION
Kidney transplantation reduces mortality and morbidity among children with ESRD.4 However, little was known about the effects of long-term immunosuppression in growing children among survivors. Herein we focused on the outcomes of a cohort of children with at least 10 years follow-up after kidney transplantation. Overall, the impact of severe long-term side effects of immunosuppression was minimal in our series. Actuarial patient and graft survivals were 97% and 86%, respectively, which were better than those reported in larger series.5,6 Most of our patients had hypertension, which is a significant risk factor for the
REFERENCES 1. Bartosh SM, Leverson G, Robillard D, et al: Long-term outcomes in pediatric renal transplant recipients who survive into adulthood. Transplantation 76:1195, 2003 2. Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 16:31, 1976 3. National Kidney Foundation, KDOQI Working Group: The definition, evaluation and classification of chronic kidney disease: getting to the heart of the matter. Am J Kidney Dis 38(S1):1398, 2001 4. Chantler C, Carter JE, Bewick M, et al: Ten years’ experience with regular haemodialysis and renal transplantation. Arch Dis Child 55:435, 1980 5. Seikaly M, Ho PL, Emmett L, et al: The 12th Annual Report of the North American Pediatric Renal Transplant Cooperative Study: renal transplantation from 1987 through 1998. Pediatr Transplant 5:215, 2001 6. Offner G, Latta K, Hoyer PF: Kidney transplanted children come of age. Kidney Int 55:1509, 1999 7. Sorof JM, Sullivan EK, Tejani A, et al: Antihypertensive medication and renal allograft failure: a North American Pediatric Renal Transplant Cooperative Study report. J Am Soc Nephrol 10:1324, 1999 8. Fine RN, Ho M, Tejani A, North American Pediatric Renal Transplant Cooperative Study (NAPRTCS): The contribution of renal transplantation to final adult height: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Nephrol 16:951, 2001 9. Englund M, Berg U, Tydén G: A longitudinal study of children who received renal transplants 10 –20 years ago. Transplantation 76:311, 2003 10. Ghio L, Garavaglia R: Renal transplantation in the pediatric age. Minerva Pediatr 55:103, 2003
R
ENAL TRANSPLANTATION has become the preferred option for children of all ages with end-stage renal disease (ESRD). Nevertheless, reports on cohorts of children who have undergone a renal transplantation and have become adults are rare.1 Herein we report the longterm outcomes of a group of pediatric recipients who reached 10 years posttransplantation, with a particular emphasis on physical and social rehabilitation. PATIENTS AND METHODS Since 1969, 458 kidney transplantations have been performed in children and adolescents younger than 21 years of age, among whom 147 patients are regularly followed at our institution. From the database, we identified 36 patients who received a kidney transplant before September 1, 1997, and therefore would have reached at least 10 years follow-up on September 1, 2007. All patients (19 males/17 females) received a deceased donor kidney (mean age of the donor, 17.2 ⫾ 14 years). Mean age at transplantation was 12.2 ⫾ 5.7 years; all but 2 patients received a primary transplant. The immunosuppressive regimen consisted of cyclosporine and prednisone. Cyclosporine was started at 500 mg/m2 with median trough levels at 10 years posttransplantation of 125 ⫾ 70 ng/mL. Prednisone was administered on alternate days from 6 months. Among this cohort, we analyzed actuarial patient and graft survivals (Kaplan-Meier), graft function (serum creatinine and estimated creatinine clearance2, nutritional and growth status as
body mass index [BMI ⫽ weight (kg)/height (m)2] and height standard deviation score [HSDS ⫽ (observed height ⫺ expected height for age)/(standard deviation of mean height for age)].
RESULTS Patient and Graft Survivals
The mean follow-up period was 14.2 ⫾ 4 years (range, 10.6 –25.8 years). At this time, the mean age of the patients was 26.4 ⫾ 6 years. Actuarial patient and graft survivals at 15 years posttransplantation were 97% and 86%, respectively. One patient died at 11 years posttransplantation due to a complicated sclerosant encapsulating peritonitis, 3 From the Division of General Surgery and Kidney Tansplant (M.F., M.R., C.B., L.B.) and Pediatric Nephrology Unit (L.G., M.B., V.M., A.E.), Mangiagalli and Regina Elena Foundation, IRCCS, Milan, Italy. This work was supported by a grant from Associazione Bambino Nefropatico (ABN), Milan, Italy. Address reprint requests to Mariano Ferraresso, MD, PhD, Division of General Surgery and Kidney Transplant, Maggiore Hospital Policlinico, Mangiagalli and Regina Elena Foundation, IRCCS, Via F. Sforza 35, 20133 Milan, Italy. E-mail: mariano. [email protected]
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.003
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1852
Transplantation Proceedings, 40, 1852–1853 (2008)
PEDIATRIC KIDNEY TRANSPLANTATION
grafts were lost from chronic rejection and 1 from noncompliance at a median time of 10.6 years. Graft Function
During the follow-up, the mean serum creatinine was 1.5 ⫾ 0.6 mg/dL and mean creatinine clearance was 66.1 ⫾ 24 mL/min. Eighteen percent of the patients presented as class 1 chronic kidney disease; 33%, class 2; and 49%, class 3, according to National Kidney Foundation guidelines.3 Growth and BMI
Median height was ⫺1.33 HSDS; 10.4% had an HSDS ⬎0, 56.6% between 0 and ⫺2; and only 27% a severe growth impairment with an HSDS ⬍⫺2. Mean BMI was 23.4 ⫾ 3.7; 24% of the patients showed a BMI between 25 and 30, and only 1 patient was obese (BMI ⬎30).
1853
development of cardiovascular disease and an independent predictor of graft survival.7 Concerning nutritional status, only 1 patient was obese and fewer than 30% were overweight. Since corticosteroids play a pivotal role in promoting weight gain after transplantation, our steroid taper, which included alternate-day low dose steroids starting at 6 months posttransplantation, may explained the good results. Finally, adult height is a significant endpoint for children with renal failure. Many authors have reported a percentage of long-term pediatric recipients with severe impairment of height ranging from 20% to 40%.8,9 In our series, only 27% of patients had an HSDS below the 3rd percentile. Since both steroid therapy and graft function have a great impact on catch-up growth,10 our results may also be explained by our steroid schedule and by the good graft function of the patients. In conclusion, our results were encouraging, supporting efforts to offer transplantation as the preferred alternative for children with ESRD.
Malignancies and Hypertension
Two patients developed B-cell lymphomas at 3 and 14 years posttransplantation. One patient developed an EBVcorrelated leiomyoma at 9 years posttransplantation. All cases were managed successfully; all patients kept their grafts functioning. Median mean arterial pressure was 97.4 ⫾ 18.8 mm Hg; 78.3% of the patients had hypertension requiring medical therapy. Social Aspects
Excluding the 2 mentally retarded patients, all but 1 had high levels of educational achievement or full-time employment. Two patients were married and 1 of them had given birth to a child. DISCUSSION
Kidney transplantation reduces mortality and morbidity among children with ESRD.4 However, little was known about the effects of long-term immunosuppression in growing children among survivors. Herein we focused on the outcomes of a cohort of children with at least 10 years follow-up after kidney transplantation. Overall, the impact of severe long-term side effects of immunosuppression was minimal in our series. Actuarial patient and graft survivals were 97% and 86%, respectively, which were better than those reported in larger series.5,6 Most of our patients had hypertension, which is a significant risk factor for the
REFERENCES 1. Bartosh SM, Leverson G, Robillard D, et al: Long-term outcomes in pediatric renal transplant recipients who survive into adulthood. Transplantation 76:1195, 2003 2. Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 16:31, 1976 3. National Kidney Foundation, KDOQI Working Group: The definition, evaluation and classification of chronic kidney disease: getting to the heart of the matter. Am J Kidney Dis 38(S1):1398, 2001 4. Chantler C, Carter JE, Bewick M, et al: Ten years’ experience with regular haemodialysis and renal transplantation. Arch Dis Child 55:435, 1980 5. Seikaly M, Ho PL, Emmett L, et al: The 12th Annual Report of the North American Pediatric Renal Transplant Cooperative Study: renal transplantation from 1987 through 1998. Pediatr Transplant 5:215, 2001 6. Offner G, Latta K, Hoyer PF: Kidney transplanted children come of age. Kidney Int 55:1509, 1999 7. Sorof JM, Sullivan EK, Tejani A, et al: Antihypertensive medication and renal allograft failure: a North American Pediatric Renal Transplant Cooperative Study report. J Am Soc Nephrol 10:1324, 1999 8. Fine RN, Ho M, Tejani A, North American Pediatric Renal Transplant Cooperative Study (NAPRTCS): The contribution of renal transplantation to final adult height: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Nephrol 16:951, 2001 9. Englund M, Berg U, Tydén G: A longitudinal study of children who received renal transplants 10 –20 years ago. Transplantation 76:311, 2003 10. Ghio L, Garavaglia R: Renal transplantation in the pediatric age. Minerva Pediatr 55:103, 2003