UROL_V3_No2_001_Editorial.qxd Urology Journal UNRC/IUA Vol. 3, No. 2, 82-86 Spring 2006 Printed in IRAN 82 Received October 2005 Accepted February 2006 *Corresponding author: Department of Kidney Transplantation, Chamran Hospital, Nobonyad Sq, Pasdaran St, Tehran, Iran. Tel: +98 912 304 6074, E-mail: hgholamrezaie@unrc.ir Kidney Transplantation En Bloc Kidney Transplantation from Pediatric Cadaveric Donors to Adult Recipients Reza Mahdavi,1 Davood Arab,1 Rahim Taghavi,1 Hamid Reza Gholamrezaie,2* Mohammad Yazdani,3 Nasser Simforoosh,4 Ali Tabibi4 1Department of Kidney Transplantation, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran 2Department of Kidney Transplantation, Chamran Hospital, Tehran Medical Branch, Islamic Azad University, Tehran, Iran 3Department of Kidney Transplantation, Khorshid Hospital, Esfahan University of Medical Sciences, Isfahan, Iran 4Department of Kidney Transplantation, Shaheed Labbafinejad Medical Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran ABSTRACT Introduction: The shortage of cadaveric donors for kidney transplantation has led to the expansion of the criteria used for donor selection, such as the use of pediatric cadaveric donors. In this study we reviewed our results of en bloc kidney transplantation of pediatric cadaveric donors to adults. Materials and Methods: From May 2001 to May 2005, 245 cadaveric kidney transplants have been performed in our hospitals. Seven of these were en bloc kidney transplantations in adult recipients from marginal pediatric donors (age < 5 years, donor weight < 15 kg, high creatinine clearance, or kidney length < 8 cm). We reviewed their records. Follow-up (range, 3 to 24 months) included ultrasonography, dimercaptosuccinic acid renal scintigraphy, and magnetic resonance imaging. Results: Serum levels of creatinine ranged between 0.8 m/dL to 1.9 mg/dL during the follow-up period. One patient died of myocardial infarction 3 months postoperatively. One-year graft and patient survivals were both 85.7%. Complications included acute tubular necrosis in 1 patient (managed by conservative therapy and dialysis for 2 weeks), renal vein thrombosis in 1 (treated by anticoagulation), and subcutaneous hematoma in 1. There were no urologic complications. Median size of the grafts was 7.2 cm preoperatively that reached 9.6 cm, 3 months postoperatively (P = .018). Twelve months following operation, the median size of the grafts reached 11 cm (P = .045). Conclusion: En bloc pediatric kidney transplantation is a safe and suitable alternative for adult recipients. One-year graft and patient survivals are acceptable and complication rate is low. KEY WORDS: kidney transplantation, pediatric donor, cadaveric donor Mahdavi et al 83 Introduction The shortage of cadaveric donors for kidney transplantation has prompted physicians to expand the criteria used for donor selection. The use of pediatric cadaveric en bloc kidneys is one of those expanded criteria.(1-3) The lower graft survival of pediatric kidney allografts due to the technical complications and hyperfiltration injury is challenging.(4,5) Several studies have shown that the outcomes of transplantation using pediatric donors are not favorable when compared with transplantation using adult donors.(6-8) However, some reports have recently revealed that survival of kidney allografts from pediatric cadaveric donors younger than 5 years is the same as those from adult donors.(8-10) In this study, we depicted our experience in transplantation of pediatric cadaveric en bloc kidney allografts to adult recipients. Materials and Methods From May 2001 to May 2005, a total of 245 cadaveric kidney transplants have been performed in our hospitals (Imam Reza Hospital in Mashhad, Shaheed Labbafinejad Medical Center and Chamran Hospital in Tehran, and Khorshid Hospital in Isfahan, Iran). Of those, 7 were en bloc kidney transplantations from marginal pediatric cadaveric donors (ie, donors with at least one of these criteria: age < 5 years, weight < 15 kg, a high creatinine clearance, and kidney length < 8 cm) which were transplanted to adult recipients. Immunosuppressive protocol was a triple therapy by prednisolone, cyclosporine, and mycophenolate mofetil. Acute rejection episodes were treated by pulse steroid and antilymphocyte globulin. The patients were followed up for 3 to 24 months. Dimercapto- succinic acid renal scintigraphy was performed during 24 months' follow-up periodically (Figure 1) and the sizes of the kidneys were evaluated by magnetic resonance imaging (MRI) and/or ultrasonography, 3 and 12 months post- operatively (Figure 2). We reviewed the hospital records of our patients retrospectively, and collected data including demographic characteristics of the kidney recipients and donors; size and weight of the kidney allografts before and after transplantation; serum creatinine levels at postoperative months 3, 6, 12, 18, and 24; complications; and the overall outcome of patient and graft. Technique. Both kidneys of pediatric cadaveric donors were harvested and irrigated with Wisconsin solution and heparinized ringer lactate in 3 and 4 cases, respectively. The kidneys were placed extraperitoneally in the iliac fossa of the recipients via a Gibson incision. In 6 patients, the FIG. 1. Dimercaptosuccinic acid renal scintigraphy in a 34- year-old woman 3 months postoperatively FIG. 2. Magnetic resonance imaging in a 43-year-old woman 3 months postoperatively En Bloc Kidney Transplantation84 aorta and the inferior vena cava (IVC) of donor were anastomosed end to side to the external iliac artery and vein with 5-0 or 6-0 prolene sutures (Figure 3), but in 1 patient, the end-to- side anastomosis was made to the recipient's aorta and IVC. To prevent kinking of renal vessels, the upper pole of the grafts was fixed to the iliopsoas muscle. The ends of the two ureters were anastomosed medially together and then ureteroneocystostomy was performed using Lich Gregoir extravesical technique, but in 1 patient, ureteroureterostomy was carried out. In all patients, ureteral stents were placed for 4 to 6 weeks. The ureteral catheter was removed 5 days postoperatively. Statistical analyses. The collected data were analyzed by SPSS software (Statistical Package for the Social Sciences, version 13, SPSS Inc, Chicago, Ill, USA). The Spearman rank correlation was used to determine the correlation between variables and Wilcoxon signed rank test to analyze the difference between size of the kidneys before and after transplantation. Kaplan- Meier method was used to determine non-death- censored graft survival and patient survival. Continuous variables were shown as medians and P values less than .05 were considered significant. Results Median age of the donors was 4.2 years (range, 2 to 8 years) and their median weight was 12 kg (range, 8 to 20 kg). Four of them were boys and 3 were girls. Median age of the recipients was 34 years (range, 13 to 42 years) and their median weight was 58 kg (range, 37 to 70 kg). Three patients received their second kidney allografts. One-year graft and patient survivals were both 85.7%. One patient died of myocardial infarction 100 days postoperatively while he had a functioning graft. The median follow-up was 12 months (range, 3 to 24 months). Delayed graft function occurred in 1 patient due to acute tubular necrosis, which was managed by medical therapy and dialysis for 2 weeks. The remaining 6 patients had a reasonable urine output early after transplantation. Complications included renal vein thrombosis in 1 patient, which was treated by anticoagulation, and subcutaneous hematoma in 1, which was drained completely. There were no reports of ureteral stenosis, ureteral leakage, or lymphocele during the follow- up period (Table 1). Serum creatinine levels ranged between 0.8 mg/dL and 1.9 mg/dL from 3 to 24 months postoperatively (Table 2). There was not any correlation between the last serum creatinine levels and the recipients' weights and ages (P = .70; P = .39). FIG. 3. End-to-side anastomosis of the aorta and the inferior vena cava (IVC) of donor to the external iliac artery and vein TABLE 1. Demographic and clinical features of the patients with en bloc kidney transplantation *The patient died of myocardial infarction 100 days postoperatively. Patients’ number Sex Age (year) Follow-up (month) Last creatinine (mg/dL) Complications 1 female 42 24 1 Subcutaneous hematoma 2 male 35 12 1.3 Acute tubular necrosis 3 female 13 18 1.2 - 4 male 25 24 1.1 Renal vein thrombosis 5 female 15 12 1.9 - 6 male 38 3 * 1 - 7 female 34 12 .8 - Mahdavi et al 85 Table 3 demonstrates the sizes of grafts measured during the follow-up. Ultrasonography and MRI revealed a significant increase in sizes of grafts during 3 to 12 month postoperatively. Median size of the grafts was 7.2 cm preoperatively and reached 9.6 cm, 3 months postoperatively (P = .018). Twelve months following operation, the median size of the grafts reached 11 cm (P = .045). Discussion Mortality of patients who are on the waiting list of kidney transplantation is about 6.3% per year in the United States, but it reaches 10% in diabetics and/or old patients.(10) Therefore, in 5 years, mortality rate exceeds 30% in nondiabetic patients who are on a waiting list.(10) A limited graft procurement cannot supply the high demand, prompting the extension of the criteria used for donor selection. Using Marginal donors including nonheart-beating donors,(11) older donors,(12) hepatitis C positive donors for recipients with hepatitis C,(13) and pediatric donors(14-16) is now considered, especially in countries whose donor source is mainly cadaveric. The use of pediatric cadaveric donors younger than 5 years old can result in a high rate of technical complications; the main challenges are a high risk of graft thrombosis, suboptimal nephron mass, frequent rejection episodes, a low graft survival, an increased rate of hyperfiltration injury, and difficulties in adjustment of immunosuppressive drugs.(17-21) Thus, pediatric donors are marginal especially when a single pediatric kidney is transplanted to an adult. Pediatric grafts can be transplanted to pediatric patients; however, there is not always a pediatric recipient available for transplantation. We encountered this problem in our centers and adult recipients were allocated for pediatric donors. To reduce the risks, we preferred en bloc kidney transplantation. Today, en bloc kidney transplantation is recommended for pediatric donors younger than 3 years, with a body weight less than 15 kg, and with a kidney length less than 8 cm.(22) Beasley and colleagues reviewed 16 en bloc pediatric kidney transplants performed in 2 centers and reported a 3-year graft survival of 94%. Two deaths with functioning grafts occurred secondary to cardiac and infectious etiologies. Graft thrombosis was not seen in any patients. Acute rejection developed in 7 patients who were treated with steroid and antilymphocyte antibody and the kidneys returned to the normal function. Other complications included 1 lymphocele and 4 ureteral complications (managed by ureteral reimplantation).(23) Between 1996 and 2002, El- Sheikh and colleagues performed 15 en bloc pediatric kidney transplants. One-year graft and patient survivals were 92.8% and 100%, respectively. There were no ureteral complications, but 1 lymphocele developed.(24) We had 1 death in our patients due to cardiac disorder. The resultant graft survival at 1 and 2 years was comparable to the survival of other cadaveric transplantations in our institutions. However, a more precise comparison is warranted with larger series. We showed that the pediatric kidney allografts had a significant increase in size following en bloc transplantation, confirmed by MRI. It can be speculated that the kidneys grow rapidly in recipient's body to support the blood volume needed to be filtrated in an adult. In accordance with our findings, Merkel has demonstrated that the size of pediatric kidneys will be doubled within 2 to 3 posttransplant weeks and it reaches the adults' size 18 months after operation.(25) In our series, 1 patient developed renal vein thrombosis 10 days postoperatively, which was treated by anticoagulation therapy. Hence, it TABLE 2. Postoperative serum creatinine levels in recipients of en bloc kidney allografts from pediatric cadaveric donors TABLE 3. Kidney allograft sizes before and after transplantation Postoperative months Serum creatinine levels (mg/ dL) 3 6 12 18 24 Median 1.2 1.05 1 1.7 1.45 Minimum .8 .8 .8 1.2 1.1 Maximum 1.9 1.9 1.9 1.7 1.8 Number of patients 7 6 6 3 2 Kidney size (cm) Before operation Three months after operation Twelve months after operation Median 7.2 9.6 11 Minimum 5.5 6.25 10 Maximum 8.5 10.5 13 Number of patients 7 7 6 En Bloc Kidney Transplantation86 seems that technical problem was not the main cause of thrombosis. There were no urologic complications such as ureteral stenosis and ureteral leakage in our study, but Drakopoulos and coworkers reported ureteral complications in 28% of en bloc transplantations in 13 patients.(6) However, the reported complications did not affect graft function in long term. In our preliminary report, 1 graft developed acute tubular necrosis. Warm and cold ischemia may play a role in this complication. Conclusion Pediatric en bloc kidney transplantation is a safe and suitable alternative for adult recipients. One-year graft and patient survivals are acceptable and complication rate is low. To confirm these findings, a long-term follow-up of larger series and prospective studies comparing the outcome with other donor sources are required. References 1. Ishikawa N, Tanabe K, Tokumoto T, et al. Transplantation of pediatric cadaveric kidneys into adult or pediatric recipients. Transplant Proc. 2004;36:2018-9. 2. Borboroglu PG, Foster CE 3rd, et al. Solitary renal allografts from pediatric cadaver donors less than 2 years of age transplanted into adult recipients. Transplantation. 2004;77:698-702. 3. Dharnidharka VR, Stevens G, Howard RJ. En-bloc kidney transplantation in the United states: an analysis of united network of organ sharing (UNOS) data from 1987 to 2003. Am J Transplant. 2005;5:1513-7. 4. Abouna GM, Kumar MS, Chvala R, McSorley M, Samhan M. Transplantation of single pediatric kidneys into adult recipients--a 12-year experience. Transplant Proc. 1995;27:2564-6. 5. Modlin C, Novick AC, Goormastic M, Hodge E, Mastrioanni B, Myles J. Long-term results with single pediatric donor kidney transplants in adult recipients. J Urol. 1996;156:890-5. 6. Drakopoulos S, Koukoulaki M, Vougas V, Apostolou T, Hadjiyannakis EI, Hadjiconstantinou V. Transplantation of pediatric kidneys to adult recipients: an analysis of 13 cases. Transplant Proc. 2004;36:3161-3. 7. Bresnahan BA, McBride MA, Cherikh WS, Hariharan S. Risk factors for renal allograft survival from pediatric cadaver donors: an analysis of united network for organ sharing data. Transplantation. 2001;72:256-61. 8. Neumayer HH, Huls S, Schreiber M, Riess R, Luft FC. Kidneys from pediatric donors: risk versus benefit. Clin Nephrol. 1994;41:94-100. 9. Kamel MH, Rampersad A, Mohan P, Hickey DP, Little DM. Cadaveric kidney transplantation in children < or =20 kg in weight: long-term single-center experience. Transplant Proc. 2005;37:685-6. 10. Meier-Kriesche H, Port FK, Ojo AO, et al. Deleterious effect of waiting time on renal transplant outcome. Transplant Proc. 2001;33:1204-6. 11. Sanchez-Fructuoso AI, Prats D, Torrente J, et al. Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool. J Am Soc Nephrol. 2000;11:350-8. 12. Andres A, Herrero JC, Praga M, et al. Double kidney transplant (dual) with kidneys from older donors and suboptimal nephronal mass. Transplant Proc. 2001;33:1166-7. 13. Morales JM, Campistol JM, Andres A, et al. Use of kidneys from anti-HCV positive donors. Transplant Proc. 2001;33:1776-7. 14. Hiramoto JS, Freise CE, Randall HR, et al. Successful long-term outcomes using pediatric en bloc kidneys for transplantation. Am J Transplant. 2002;2:337-42. 15. Gourlay W, Stothers L, McLoughlin MG, Manson AD, Keown P. Transplantation of pediatric cadaver kidneys into adult recipients. J Urol. 1995;153:322-5 6. 16. Strey C, Grotz W, Mutz C, et al. Graft survival and graft function of pediatric en bloc kidneys in paraaortal position. Transplantation. 2002;73:1095-9. 17. Hayes JM, Novick AC, Streem SB, et al. The use of single pediatric cadaver kidneys for transplantation. Transplantation. 1988;45:106-10. 18. Satterthwaite R, Aswad S, Sunga V, et al. Outcome of en bloc and single kidney transplantation from very young cadaveric donors. Transplantation. 1997;63:1405-10. 19. Terasaki PI, Gjertson DW, Cecka JM, Takemoto S, Cho YW. Significance of the donor age effect on kidney transplants. Clin Transplant. 1997;11:366-72. 20. Smith AY, Van Buren CT, Lewis RM, et al. The outcome of repeat cadaveric kidney transplants in recipients managed with cyclosporine. Transplant Proc. 1988;20:180-93. 21. Hayes JM, Steinmuller DR, Streem SB, Novick AC. The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys. Transplantation. 1991;52:813-7. 22. Ko DSC, Delmonico FL. Surgical aspect of renal transplantation. In: Owen WF, Pereira BJG, Sayegh MH, editors. Dialysis and transplantation: a companion to Brenner & Rector's the kidney. Philadelphia: WB Saunders; 2000. p. 542-3. 23. Beasley KA, Balbontin F, Cook A, et al. Long-term follow- up of pediatric en bloc renal transplantation. Transplant Proc. 2003;35:2398-9. 24. El-Sheikh MF, Gok MA, Buckley PE, et al. En bloc pediatric into adult recipients: the Newcastle experience. Transplant Proc. 2003;35:786-8. 25. Merkel FK. Five and 10 year follow-up of En Bloc small pediatric kidneys in adult recipients. Transplant Proc. 2001;33:1168-9.