- Email: [email protected]
Results of En Bloc Renal Transplants of Pediatric Deceased Donors into Adult Recipients
Results of En Bloc Renal Transplants of Pediatric Deceased Donors into Adult Recipients E. Keitel, L.R. Fasolo, A.R. D’Avila, E.C. Didone, A.F. Santos, L.M. Rocha, S.P. Vitola, E.E. Guerra, F.S. Pires, J.G. Silva, and V.D. Garcia ABSTRACT Various strategies have evolved to expand the donor pool due to the extreme shortage of organs. Herein we reviewed our experience with en bloc pediatric kidney transplantation since 1998. Methods. From January 1998 to December 2004, nine adult patients underwent kidney transplantation using en bloc kidneys from donors ⬍5 years old (range, 1 to 4). The mean age of the recipients was 45.1 years (range, 34 to 57). Results. In recipients of en bloc pediatric transplantation, cold ischemia time ranged from 14 to 26.2 hours (mean, 21.3 hours). Mean serum creatinine at 3, 6, and 12 months after transplantation was 1.53 ⫾ 0.57, 1.27 ⫾ 0.27, and 1.15 ⫾ 0.26 mg/dL compared with 1.93 ⫾ 1.35, 1.81 ⫾ 1.17, and 1.73 ⫾ 0.85 (P ⫽ .08) in recipients of single kidneys from ideal cadaveric donors (UNOS criteria, n ⫽ 368). Patient and graft survival at 1 year were 88.8% compared with 91.2% and 85% with ideal donors (P ⫽ NS), respectively. Three cases required additional surgery. There was one death due to a cerebral vascular accident. Conclusion. The present study confirmed the excellent results achieved with transplantation using en bloc kidneys from young donors.
O
NE OF THE MAIN problems in transplantation is the shortage of donors. Several strategies have been developed to address this issue, including the use of expanded criteria donors (ECDs). In kidney transplantation, ECDs are not only older patients with impaired renal function, but also pediatric patients whose renal mass may be considered insufficient to function properly in an adult. There is no definitive guideline on how to use these organs: they can be used either as single or double kidney grafts. Some studies have shown that en bloc transplant is recommended for kidneys from donors 5 years old. The donor weight is the most important variable to predict the outcome. For children ⬎5 years old, donor age seems to be a most important variable.1 Lower or similar graft survival with pediatric donors has been described.1,2 However, en bloc pediatric donors seem to experience more surgical complications.2 We reviewed our experience with pediatric en bloc kidney transplantation between 1998 and 2004. We analyzed surgical complications, graft function at 3, 6, and 12 months as well as patient and graft survivals. METHODS From January 1998 to December 2004, nine pediatric donors were transplanted as en bloc kidneys into adult recipients at our © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 441– 442 (2007)
institution. Donor ranged from age 1 to 4 years old (mean; 2.56 ⫾ 0.76). Five donors were boys. We compared this group with 368 renal transplants with ideal decreased donors performed during the same period. The mean age of the recipients at transplantation was 45.1 ⫾ 7.9 years versus 41.3 ⫾ 3.6 years. There were 88.8% and 92.3% primary transplants, respectively. Seven recipients of en bloc kidneys received induction therapy (one ATG and six IL-2 receptor antagonists). Five patients received cyclosporine- and four tacrolimusbased immunosuppression. Mean values were compare by independent t tests and survivals by the Kaplan–Meier method with P significant at ⬍.05.
Technical Aspects The kidneys were removed en bloc with an intact segment of aorta and inferior vena cava after systemic heparinization and in situ From the Nephrology Service- Renal and Pancreas Transplant Unit (E.K., A.R.D., E.C.D., A.F.S., S.P.V., E.E.G., F.S.P., J.G.S., V.D.G.) and the Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (E.K., L.R.F., L.M.R.), Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil. Address reprint requests to Valter Duro Garcia Av. Independência, 155. HDVS - 6° andar. Complexo Hospitalar Santa Casa de Porto Alegre Porto Alegre, RS-Brazil 90025090. E-mail: [email protected] 0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.01.029 441
442 perfusion with 1500 to 2000 mL of chilled University of Wisconsin or Euro-Collins solution. The ureters were sectioned as close to the bladder as possible and the entire block removed. In the bench dissection, the proximal end of the aorta and vena cava were oversewen and the lumbar vessels carefully ligated. In the recipient, the external iliac artery and vein were isolated through a right or left Gibson incision. The distal end of the aorta and vena cava were anastomosed end-to-side to the iliac vessels. The ureteral anastomosis to the bladder was performed either separately or with a single orifice after joining them with a running suture. In one patient, the ureters were sutured to an ileal conduit because of a previous cystectomy.
RESULTS
Comparing pediatric donors (n ⫽ 9) with adult ideal donors (n ⫽ 368), the cold ischemia time was 21.3 ⫾ 5 versus 20.9 ⫾ 5.5 hours. Delayed graft function was 55.6% versus 66%. Mean serum creatinine at 3, 6, and 12 months after transplantation were 1.53 ⫾ 0.57, 1.27 ⫾ 0.27, and 1.15 ⫾ 0.26 mg/dL compared with 1.93 ⫾ 1.35, 1.81 ⫾ 1.17, and 1.73 ⫾ 0.85 mg/dL, (P ⫽ .08). Patient and graft 1-year survivals were 88.8% and 88.8% versus 91.2% and 85%, respectively (P ⫽ NS). One patient lost one graft on day 4 from renal rupture, most likely related to venous thrombosis, however mantaining adequate renal function: creatinine at 1 year after transplantation was 1.2 mg/dL. In one patient a perirenal hematoma resolved with surgical drainage. A third patient with urethral stenosis secondary to urinary tuberculosis and previous urinary diversion surgery (ileal conduit) needed multiple reinterventions to control bleeding, infection, and a urinary leak. Two biopsies demonstrated acute tubular necrosis. Still, grafts maintained function, and at 7 months after transplantation creatinine was 1.7 mg/dL. One month later, however, a massive hemorrhagic stroke lead her to death. The remaining patients have functioning grafts. DISCUSSION
According to the current literature, pediatric donor en bloc kidney transplantation is an alternative to utilize organs that would be discarded otherwise. The main problem is the increased frequence of vascular complications, especially vascular thrombosis, leading to graft loss. UNOS data showed 10% vascular thrombosis using donors ⬍5 years old compared with 5% among donors between 12 and 17 years old. They also showed better results using en bloc kidneys from donors ⬍5 years old compared with single grafts from
KEITEL, FASOLO, D’AVILA ET AL
donors whose weight was ⬎15 kg. However, recipients of previous transplants, prolonged ischemia time, black recipients, and those with a body mass index ⬎24 were considered risk factors for poor results.1 Trying to increase the number of kidneys available for transplantation, Borgoroglu et al4 showed that kidneys from pediatric donors ⬍2 years old (but at least 6 cm length and donor weight ⬎14 kg) can be implanted as single grafts with similar results to en bloc grafts. Recently, similar findings were published by El-Sabrout et al.5 They observed a lower incidence of acute rejection episodes with tacrolimus-compared to cyclosporinebased immunosuppression.5 Interestingly, in both studies an higher incidence of graft loss due to vascular thrombosis were seen in the en bloc than in single transplants. Beyond the short-term complications, late graft function is a concern. Addressing this issue, a long-term retrospective comparation between 75 living donor kidneys and 72 pediatric en bloc renal allografts was done. They observed significantly better renal function in pediatric en bloc kidney recipients (glomerular filtration rate 61.6 ⫾ 25.2 versus 38.4 ⫾ 16.1 mL/min/1.73 m2). There was a longitudinal increment in glomerular filtration rate up to 5 years in the en bloc group, whereas there was a trend toward a longitudinal decrement in glomerular filtration rate among the living donor group. The incidence and amount of proteinuria were similar in both groups. The present work confirmed the excellent results achieved with transplantation of en bloc kidneys from young donors. It is important to search for variables that may affect outcomes when using ECD kidneys, to establish guidelines determining the use of single versus en bloc kidneys.3 REFERENCES 1. Bresnahan BA, McBride MA, Cherikh WS, et al: Risk factors for renal allograft survival from pediatric cadaver donors: an analysis of united network for organ sharing data. Transplantation 72:256, 2001 2. Hobart MG, Modlin CS, Kapoor A, et al: Transplantation of pediatric en bloc cadaver kidneys into adult recipients. Transplantation 66:1689, 1998 3. Borgoroglu PG, Foster CE, Philosophe B, et al: Solitary renal allografts from pediatric cadaver donors less than 2 years of age transplanted into adult recipients. Transplantation 77:698, 2004 4. El-Sabrout R, Buch K: Outcome of renal transplants from pediatric donors ⬍5 yr of age. Clin Transplant 19:316, 2005 5. Tan JC, Alfrey JE, Dafoe DC, et al: Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 78:692, 2004
O
NE OF THE MAIN problems in transplantation is the shortage of donors. Several strategies have been developed to address this issue, including the use of expanded criteria donors (ECDs). In kidney transplantation, ECDs are not only older patients with impaired renal function, but also pediatric patients whose renal mass may be considered insufficient to function properly in an adult. There is no definitive guideline on how to use these organs: they can be used either as single or double kidney grafts. Some studies have shown that en bloc transplant is recommended for kidneys from donors 5 years old. The donor weight is the most important variable to predict the outcome. For children ⬎5 years old, donor age seems to be a most important variable.1 Lower or similar graft survival with pediatric donors has been described.1,2 However, en bloc pediatric donors seem to experience more surgical complications.2 We reviewed our experience with pediatric en bloc kidney transplantation between 1998 and 2004. We analyzed surgical complications, graft function at 3, 6, and 12 months as well as patient and graft survivals. METHODS From January 1998 to December 2004, nine pediatric donors were transplanted as en bloc kidneys into adult recipients at our © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 441– 442 (2007)
institution. Donor ranged from age 1 to 4 years old (mean; 2.56 ⫾ 0.76). Five donors were boys. We compared this group with 368 renal transplants with ideal decreased donors performed during the same period. The mean age of the recipients at transplantation was 45.1 ⫾ 7.9 years versus 41.3 ⫾ 3.6 years. There were 88.8% and 92.3% primary transplants, respectively. Seven recipients of en bloc kidneys received induction therapy (one ATG and six IL-2 receptor antagonists). Five patients received cyclosporine- and four tacrolimusbased immunosuppression. Mean values were compare by independent t tests and survivals by the Kaplan–Meier method with P significant at ⬍.05.
Technical Aspects The kidneys were removed en bloc with an intact segment of aorta and inferior vena cava after systemic heparinization and in situ From the Nephrology Service- Renal and Pancreas Transplant Unit (E.K., A.R.D., E.C.D., A.F.S., S.P.V., E.E.G., F.S.P., J.G.S., V.D.G.) and the Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (E.K., L.R.F., L.M.R.), Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil. Address reprint requests to Valter Duro Garcia Av. Independência, 155. HDVS - 6° andar. Complexo Hospitalar Santa Casa de Porto Alegre Porto Alegre, RS-Brazil 90025090. E-mail: [email protected] 0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.01.029 441
442 perfusion with 1500 to 2000 mL of chilled University of Wisconsin or Euro-Collins solution. The ureters were sectioned as close to the bladder as possible and the entire block removed. In the bench dissection, the proximal end of the aorta and vena cava were oversewen and the lumbar vessels carefully ligated. In the recipient, the external iliac artery and vein were isolated through a right or left Gibson incision. The distal end of the aorta and vena cava were anastomosed end-to-side to the iliac vessels. The ureteral anastomosis to the bladder was performed either separately or with a single orifice after joining them with a running suture. In one patient, the ureters were sutured to an ileal conduit because of a previous cystectomy.
RESULTS
Comparing pediatric donors (n ⫽ 9) with adult ideal donors (n ⫽ 368), the cold ischemia time was 21.3 ⫾ 5 versus 20.9 ⫾ 5.5 hours. Delayed graft function was 55.6% versus 66%. Mean serum creatinine at 3, 6, and 12 months after transplantation were 1.53 ⫾ 0.57, 1.27 ⫾ 0.27, and 1.15 ⫾ 0.26 mg/dL compared with 1.93 ⫾ 1.35, 1.81 ⫾ 1.17, and 1.73 ⫾ 0.85 mg/dL, (P ⫽ .08). Patient and graft 1-year survivals were 88.8% and 88.8% versus 91.2% and 85%, respectively (P ⫽ NS). One patient lost one graft on day 4 from renal rupture, most likely related to venous thrombosis, however mantaining adequate renal function: creatinine at 1 year after transplantation was 1.2 mg/dL. In one patient a perirenal hematoma resolved with surgical drainage. A third patient with urethral stenosis secondary to urinary tuberculosis and previous urinary diversion surgery (ileal conduit) needed multiple reinterventions to control bleeding, infection, and a urinary leak. Two biopsies demonstrated acute tubular necrosis. Still, grafts maintained function, and at 7 months after transplantation creatinine was 1.7 mg/dL. One month later, however, a massive hemorrhagic stroke lead her to death. The remaining patients have functioning grafts. DISCUSSION
According to the current literature, pediatric donor en bloc kidney transplantation is an alternative to utilize organs that would be discarded otherwise. The main problem is the increased frequence of vascular complications, especially vascular thrombosis, leading to graft loss. UNOS data showed 10% vascular thrombosis using donors ⬍5 years old compared with 5% among donors between 12 and 17 years old. They also showed better results using en bloc kidneys from donors ⬍5 years old compared with single grafts from
KEITEL, FASOLO, D’AVILA ET AL
donors whose weight was ⬎15 kg. However, recipients of previous transplants, prolonged ischemia time, black recipients, and those with a body mass index ⬎24 were considered risk factors for poor results.1 Trying to increase the number of kidneys available for transplantation, Borgoroglu et al4 showed that kidneys from pediatric donors ⬍2 years old (but at least 6 cm length and donor weight ⬎14 kg) can be implanted as single grafts with similar results to en bloc grafts. Recently, similar findings were published by El-Sabrout et al.5 They observed a lower incidence of acute rejection episodes with tacrolimus-compared to cyclosporinebased immunosuppression.5 Interestingly, in both studies an higher incidence of graft loss due to vascular thrombosis were seen in the en bloc than in single transplants. Beyond the short-term complications, late graft function is a concern. Addressing this issue, a long-term retrospective comparation between 75 living donor kidneys and 72 pediatric en bloc renal allografts was done. They observed significantly better renal function in pediatric en bloc kidney recipients (glomerular filtration rate 61.6 ⫾ 25.2 versus 38.4 ⫾ 16.1 mL/min/1.73 m2). There was a longitudinal increment in glomerular filtration rate up to 5 years in the en bloc group, whereas there was a trend toward a longitudinal decrement in glomerular filtration rate among the living donor group. The incidence and amount of proteinuria were similar in both groups. The present work confirmed the excellent results achieved with transplantation of en bloc kidneys from young donors. It is important to search for variables that may affect outcomes when using ECD kidneys, to establish guidelines determining the use of single versus en bloc kidneys.3 REFERENCES 1. Bresnahan BA, McBride MA, Cherikh WS, et al: Risk factors for renal allograft survival from pediatric cadaver donors: an analysis of united network for organ sharing data. Transplantation 72:256, 2001 2. Hobart MG, Modlin CS, Kapoor A, et al: Transplantation of pediatric en bloc cadaver kidneys into adult recipients. Transplantation 66:1689, 1998 3. Borgoroglu PG, Foster CE, Philosophe B, et al: Solitary renal allografts from pediatric cadaver donors less than 2 years of age transplanted into adult recipients. Transplantation 77:698, 2004 4. El-Sabrout R, Buch K: Outcome of renal transplants from pediatric donors ⬍5 yr of age. Clin Transplant 19:316, 2005 5. Tan JC, Alfrey JE, Dafoe DC, et al: Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 78:692, 2004