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Cadaver Donor Kidney Retransplantation in the Pediatric Patient: Complications and Long-Term Outcome
Cadaver Donor Kidney Retransplantation in the Pediatric Patient: Complications and Long-Term Outcome Enrique Lledó-García,* Carlos Hernández-Fernández, David Subirá-Ríos, José Maria Díez-Cordero, Ramón Durán-Merino, Felipe Herranz-Amo, Fernando Verdú-Tartajo, Mercedes Moralejo-Gárate, Gonzalo Bueno-Chomón, Gabriel Ogaya-Pinies, Dolores Morales and Augusto Luque-de Pablos From the Departments of Urology and Pediatric Nephrology (DM, ALdP), Hospital General Universitario Gregorio Marañón, Madrid, Spain
Abbreviations and Acronyms CIT ⫽ cold ischemia time DGF ⫽ delayed graft function ESRD ⫽ end stage renal disease KT ⫽ kidney transplantation * Correspondence: Servicio de Urología, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo, 46, 28007 Madrid, Spain.
Purpose: We compared the outcome of second and third kidney allografts with that of the first kidney allograft in pediatric recipients. Materials and Methods: We classified 173 cadaveric kidney recipients into 2 groups. Group 1 comprised 120 first transplants and group 2 comprised 53 retransplants, including 43 second and 10 third transplants. We compared demographic characteristics and survival in groups 1 and 2. Results: Group 1 consisted of 78 boys and 42 girls with a mean ⫾ SD age of 11.5 ⫾ 4.2 years. Group 2 consisted of 37 boys and 16 girls with a mean age of 10.4 ⫾ 4.7 years. One, 5, 10 and 15-year graft survival rates were 78.7%, 64.3%, 54.5% and 50.7% for first transplants vs 82.8%, 57.8%, 57.8% and 41.3%, respectively, for retransplants (p ⫽ 0.757). Patient survival at 1, 5 and 15-year was 95.8%, 89.6%, 84.9% in the first transplant group vs 93.6%, 93.6% and 93.6%, respectively, in the retransplant group (p ⫽ 0.0.63). Graft survival was significantly higher in patients who did vs did not receive calcineurin inhibitors in the 2 groups (p ⫽ 0.02). Conclusions: Kidney retransplantation in the pediatric population can yield excellent long-term outcomes, especially in patients treated with calcineurin inhibitors. Key Words: kidney transplantation, reoperation, tissue donors, cadaver, survival
2582
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KIDNEY transplantation is the treatment of choice in children with ESRD.1 Advances in immunosuppression and improvements in the surgical skills involved in performing transplantation in children have resulted in improved outcomes for this treatment modality. The success of the procedure has created a demand for the operation. We compared second and third cadaver donor KT with the first transplantation in pediatric patients. We analyzed the incidence of delayed graft function, midterm and long-term serum creatinine,
We retrospectively reviewed the charts of 173 cadaver donor KTs in pediatric patients done at our center from 1978 through 2006. There were 120 first transplants (group 1) and 53 retransplants, including 43 second and 10 third transplants (group 2). Mean ⫾ SD donor age was 9.3 years (range 0 to 48) years. Mean recipient age was 11 years (range 7.5 to 15) in group 1 and 14.9 years (range 3 to 15) in group 2. The most common cause of ESRD in groups
0022-5347/11/1856-2582/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 185, 2582-2585, June 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.01.028
complications, and actuarial graft and patient survival.
MATERIALS AND METHODS
AND
RESEARCH, INC.
CADAVER DONOR KIDNEY RETRANSPLANTATION COMPLICATIONS AND OUTCOME
Demographics in groups 1 and 2 Characteristic (group No.) Recipient age: 1 2 Donor age: 1 2 HLA match: 1 2 HLA-DR match: 1 2 CIT (hrs): 1 2 DGF (days): 1 2 1-yr Serum creatinine (mg/dl): 1 2 5-yr Serum creatinine (mg/dl): 1 2 10-yr Serum creatinine (mg/dl): 1 2 No. rejection episodes: 1 2
Mean ⫾ SD
p Value 0.4
11.504 ⫾ 4.2279 10.414 ⫾ 4.709 0.2 9.93 ⫾ 13.65 19.3 ⫾ 9.26 0.08 0.63 ⫾ 0.576 0.80 ⫾ 0.447 0.55 0.79 ⫾ 0.658 1.20 ⫾ 0.837 0.18 24.6 24.8
⫾ 6.83 ⫾ 1.78 0.32
13.56 ⫾ 9.3 10.67 ⫾ 2.3 0.39 1.12 ⫾ 0.56 1.22 ⫾ 0.65 0.16 1.13 ⫾ 0.47 1.05 ⫾ 0.15 0.73 1.14 ⫾ 0.41 1.11 ⫾ 0.33 0.31 0.6 1.4
⫾ 1.0 ⫾ 0.5
1 and 2 was glomerulonephritis (43% and 41%, p ⫽ 0.8), followed by vesicoureteral reflux (22% and 20%, p ⫽ 0.6) and congenital renal anomalies such as multicystic kidney and posterior urethral valves (15% and 18%, respectively, p ⫽ 0.65). Several immunosuppression schedules were administered during the study period. Regimens containing prednisone plus azathioprine were used from 1978 to 1990. Calcineurin inhibitors were introduced in 1990. Cyclosporine A plus prednisone plus azathioprine was administered from June 1990 to June 1996. From July 1996 to 2006 cyclosporine was replaced by tacrolimus (FK506). Mycophenolate mofetil replaced azathioprine in 2005. In patients undergoing retransplantation and those at high immune risk treatment was induced with monoclonal or polyclonal antibodies. We analyzed the DGF rate, vascular complications, acute rejection episodes and serum creatinine at 1, 5, 10 and 15 years. Differences were estimated using the Student t test. Actuarial graft and patient survival was determined at the same time points using Kaplan-Meier log rank plots. A Cox regression model was developed to estimate the relationship between survival and several independent exploratory variables. Statistical significance was considered at p ⬍0.05.
2583
sity of Wisconsin solution in 52.6% of cases and Euro-Collins solution in 47.4%. No significant differences were observed in donor or receptor age, HLAB/DR match, CIT or DGF duration. Kidneys were implanted in the iliac fossa in 153 cases (91.2%) with vascular anastomosis to the iliac vessels. The transperitoneal approach with vascular anastomosis to the aorta and cava was used when the recipient was younger than 4 years or weighed less than 20 kg and in the 20 (8.8%) who received a third transplant due to extensive fibrosis. Ureteral reimplantation was done using the Paquin technique. Since 2003, the Taguchi 1-stitch technique has been used. The incidence of DGF in first transplant cases was slightly higher than in retransplant cases but this difference was not significant (42.5% vs 35.8%, p ⫽ 0.08). Median CIT in groups 1 and 2 was high with no significant differences, including 27 hours in group 1 vs 24 hours in group 2 (p ⫽ 0.3). The cumulative incidence of acute rejection episodes in group 1 was lower than that of repeat grafts but the difference was not statistically significant (42% vs 46.7%, p ⫽ 0.25). There were no significant differences in graft survival between first transplants and retransplants for all followup periods (log rank p ⫽ 0.757, fig. 1). Allograft half-life survival was 9.05 years (range 7.95 to 10.15) years for the first grafts and 9.07 years (range 6.66 to 11.49) for retransplants. The patient survival rate at 1, 5 and 15 years was 95.8%, 89.6% and 84.9% in group 1, respectively, and 93.6% in group 2 for all periods (p ⫽ 0.25). Calcineurin inhibitor administration improved 1-year and long-term graft survival in each group (log rank p ⫽ 0.02, fig. 2). Graft survival half-life was 8 years (range 6.7 to 9.4) before the introduction of
RESULTS The table lists the characteristics of the 2 groups. Kidneys were placed in cold storage using Univer-
Figure 1. Initial (blue curve) and repeat (green curve) kidney transplant cumulative survival.
2584
CADAVER DONOR KIDNEY RETRANSPLANTATION COMPLICATIONS AND OUTCOME
Figure 2. Kidney graft cumulative survival in patients with (green curves) vs without (blue curves) calcineurin inhibitor. A, initial transplant. B, transplants 2 and 3.
calcineurin inhibitors and 10.3 years (range 8.8 to 10.8) thereafter. The incidence of acute rejection episodes was also significantly lower for first transplants and retransplants when calcineurin inhibitors were used (log rank p ⫽ 0.001). Vascular complications developed in 9 patients (7.5%) in group 1, including arterial thrombosis in 4, venous thrombosis in 3 and renal artery stenos in 2, and in 5 (5.6%) in group 2, including arterial thrombosis in 4 and venous thrombosis in 1 (p ⬎0.05). A total of 65 grafts (54.1%) were lost in group 1 due to immunological reasons in 53 (81.5%) (chronic rejection in 41 and refractory acute rejection in 12), vascular complications in 7 (10.7%) and recurrent renal disease in 5 (7.8%). A total of 22 grafts (41.5%) were lost in group 2 due to immunological reasons in 17 (chronic rejection in 14 and refractory acute rejection in 3) and vascular causes in 5 (9.4%) (p ⫽ 0.03). Of the 30 patients who underwent retransplantation and an immunosuppressive regimen without calcineurin inhibitors the graft was lost in 14 (46%), of whom 9 (64%) experienced refractory rejection with the graft lost in year 1 after transplantation. After the systematic introduction of calcineurin inhibitors the graft was lost in 8 of 23 retransplantation cases (34.7%), including 3 due to nonadherence, 1 due to nephropathy relapse and 4 due to refractory rejection. Only 3 of these grafts (37.5%) lost function during year 1 after transplantation. A significant difference was observed in the total retransplant graft loss rate before vs after the introduction of calcineurin inhibitors (46% vs 34.7%, p ⫽ 0.04).
DISCUSSION KT is the treatment of choice in children with ESRD.1 Advances in immunosuppression and improvements in surgical techniques in children have resulted in improved outcomes. The success of this
approach has created a demand for the operation. We report the long-term outcome of 173 cadaver donor KTs in a pediatric population. We compared the effects of initial transplantation with those of retransplantation. The main cause of renal insufficiency in our series was glomerular disease, followed by abnormalities with no differences between the groups. García et al reported that in infants and young children congenital conditions and renal dysplasia lead to renal failure but in older children acquired renal disease (glomerulonephritis) leads to renal failure.2 In our groups no significant differences were observed in graft outcome, or in patient or graft survival according to the cause of ESRD. CIT was more than 24 hours in each group, which may explain the significant rate of delayed graft failure. Others also reported the negative effect of CIT and an evident detrimental effect on initial graft function, especially when it lasts more than 24 hours.3 van Lieburg et al reported a high (12%) incidence of vascular complications in pediatric recipients.4 A possible explanation is the combination of young age and low body weight in recipients, and the young age of donors as well as the high preoperative urine production. Children with hypoplastic or dysplastic kidneys are at greater risk for thrombosis. It may be possible to prevent thrombosis by administering albumin and fluids. We did not take any special measures other than applying a meticulous surgical technique. None of our patients received pharmacological prophylaxis for thrombosis. Regarding functional outcome, in a long-term study of pediatric kidney transplant recipients Schurman and McEnery reported 62% graft survival at 1 year and a 60% rate for retransplants with no significant effect of calcineurin inhibitors on long-term kidney graft survival.5 Shapiro and Sarwal reported a global rate of 1-year kidney graft survival in pediatric first transplant recipi-
CADAVER DONOR KIDNEY RETRANSPLANTATION COMPLICATIONS AND OUTCOME
ents of 93% for living donor organs and 77% for cadaver donor organs.6 Ferraresso et al reported an 86% 15-year graft survival rate in 36 first kidney transplant recipients treated with cyclosporine.7 Our 1-year cadaver graft survival rates were higher for first transplants and retransplants (78.7% and 82.8%, respectively). We did not observe significant differences in the long-term functional outcome (p ⫽ 0.757). A higher incidence of acute and chronic rejection is recognized in most series of pediatric kidney recipients.2 This could be due to a more vigorous immune response to the graft, which is hard to control using immunosuppressive regimens that systematically include monoclonal and polyclonal antibodies, calcineurin inhibitors (tacrolimus) and mycophenolate mofetil. These patients commonly have a high number of reactive antibodies, which explains why rejection is the most common cause of graft loss in pediatric recipients.2 The introduction of calcineurin inhibitors in our pediatric KT program in 1990 significantly improved 1-year graft survival for first transplants and retransplants (p ⫽ 0.02). As observed previously,8 the incidence of acute rejection was considerably decreased in patients who received calcineurin inhibitors for initial and repeat KT (p ⫽ 0.001). Cyclosporine and tacrolimus share the same pharmacodynamic property of activated T-cell suppression via calcineurin inhibition and they lead to a considerably improved outcome. Another interesting approach is the replacement of azathioprine by alternatives such as mycophenolate mofetil,9 as in our program. Cyclosporine is being successfully replaced by tacrolimus.10 Also, administering pro-
2585
phylactic basiliximab in pediatric kidney transplant recipients has significantly decreased the occurrence of acute rejection episodes.11 Routine pretransplant induction with monoclonal antibodies, polyclonal antibodies and thymoglobulin has decreased the incidence of acute rejection and increased graft tolerance. It is well known that longterm graft survival is associated with a lower incidence of acute rejection.12 Overall survival rates at 1, 2 and 5 years were reported to be 98%, 97% and 95% in living donor recipients, and 97%, 95% and 92% in recipients of cadaver organs.3 In our series the patient survival rate at 1, 5 and 15 years was 95.8%, 89.6% and 84.9% in group 1, respectively, and 93.6% in group 2 for all 3 periods (p ⫽ 0.25). Poor adherence to treatment is a reason why transplants in adolescents and young adults can show lower midterm and long-term survival.13,14 Adaptation to the situation of the patient in this subgroup can be complex and requires special care by the pediatric nephrologist. We recorded 3 cases of loss of a second graft due to nonadherence, representing 16.6% of the total number of lost second transplants.
CONCLUSIONS We report a 28-year experience with cadaveric donor KT in pediatric patients. We found no differences in long-term graft survival between first transplants and retransplants. Nonetheless, the impact of immunosuppressive agents (calcineurin inhibitors) was highly significant with better midterm and long-term results in first transplant and retransplant cases.
REFERENCES 1. Salvatierra O Jr: Pediatric renal transplantation. Transplant Proc 1999; 31: 1782.
6. Shapiro R and Sarwal MM: Pediatric kidney transplantation. Pediatr Clin N Am 2010; 57: 393.
2. García CD, Bittencourt VB, Tumelero A et al: 300 Pediatric renal transplantations: a single-center experience. Transplant Proc 2006; 38: 3454.
7. Ferraresso M, Ghio L, Raiteri L et al: Pediatric kidney transplantation: a snapshot 10 years later. Transplant Proc 2008; 40: 1852.
3. Al-Akash SI and Ettenger RB: Trasplante de riñón en niños. In: Trasplante Renal. Edited by GM Danovitch. Marbán, Spain: Lippincott Williams & Wilkins 2002.
8. Kapturczak MH, Meier-Kriesche HU and Kaplan B: Pharmacology of calcineurin antagonists. Transplant Proc, suppl., 2004; 36: 25S.
12. Parada B, Figuereido A, Nunes P et al: Pediatric renal transplantation: comparative study with renal transplantation in the adult population. Transplant Proc 2005; 37: 2771.
4. van Lieburg AF, de Jong MC, Hoitsma AJ et al: Renal transplant thrombosis in children. J Pediatr Surg 1995; 30: 615.
9. Otukesh H and Sharifian M: Mycophenolate mofetil in pediatric kidney transplants. Transplant Proc 2005; 37: 3012.
13. Giessing M, Muller D, Winkelmann B et al: Kidney transplantation in children and adolescents. Transplant Proc 2007; 39: 2197.
5. Schurman SJ and McEnery PT: Factors influencing short-term and long-term pediatric renal transplant survival. J Pediatr 1997; 130: 455.
10. Morales JM and Andrés A: Ten years of treatment with tacrolimus. Transplant Proc 2005; 37: 3738.
14. Laederach-Hofmann K and Bunzel B: Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry 2000; 22: 412.
11. García Meseguer C, Vila López A, Luque de Pablos A et al: Immunoprophylaxis with simulect (basiliximab) in pediatric kidney transplant recipients: results from routine clinical practice at 5 kidney transplant units. Transplant Proc 2003; 35: 1697.
Abbreviations and Acronyms CIT ⫽ cold ischemia time DGF ⫽ delayed graft function ESRD ⫽ end stage renal disease KT ⫽ kidney transplantation * Correspondence: Servicio de Urología, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo, 46, 28007 Madrid, Spain.
Purpose: We compared the outcome of second and third kidney allografts with that of the first kidney allograft in pediatric recipients. Materials and Methods: We classified 173 cadaveric kidney recipients into 2 groups. Group 1 comprised 120 first transplants and group 2 comprised 53 retransplants, including 43 second and 10 third transplants. We compared demographic characteristics and survival in groups 1 and 2. Results: Group 1 consisted of 78 boys and 42 girls with a mean ⫾ SD age of 11.5 ⫾ 4.2 years. Group 2 consisted of 37 boys and 16 girls with a mean age of 10.4 ⫾ 4.7 years. One, 5, 10 and 15-year graft survival rates were 78.7%, 64.3%, 54.5% and 50.7% for first transplants vs 82.8%, 57.8%, 57.8% and 41.3%, respectively, for retransplants (p ⫽ 0.757). Patient survival at 1, 5 and 15-year was 95.8%, 89.6%, 84.9% in the first transplant group vs 93.6%, 93.6% and 93.6%, respectively, in the retransplant group (p ⫽ 0.0.63). Graft survival was significantly higher in patients who did vs did not receive calcineurin inhibitors in the 2 groups (p ⫽ 0.02). Conclusions: Kidney retransplantation in the pediatric population can yield excellent long-term outcomes, especially in patients treated with calcineurin inhibitors. Key Words: kidney transplantation, reoperation, tissue donors, cadaver, survival
2582
www.jurology.com
KIDNEY transplantation is the treatment of choice in children with ESRD.1 Advances in immunosuppression and improvements in the surgical skills involved in performing transplantation in children have resulted in improved outcomes for this treatment modality. The success of the procedure has created a demand for the operation. We compared second and third cadaver donor KT with the first transplantation in pediatric patients. We analyzed the incidence of delayed graft function, midterm and long-term serum creatinine,
We retrospectively reviewed the charts of 173 cadaver donor KTs in pediatric patients done at our center from 1978 through 2006. There were 120 first transplants (group 1) and 53 retransplants, including 43 second and 10 third transplants (group 2). Mean ⫾ SD donor age was 9.3 years (range 0 to 48) years. Mean recipient age was 11 years (range 7.5 to 15) in group 1 and 14.9 years (range 3 to 15) in group 2. The most common cause of ESRD in groups
0022-5347/11/1856-2582/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 185, 2582-2585, June 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.01.028
complications, and actuarial graft and patient survival.
MATERIALS AND METHODS
AND
RESEARCH, INC.
CADAVER DONOR KIDNEY RETRANSPLANTATION COMPLICATIONS AND OUTCOME
Demographics in groups 1 and 2 Characteristic (group No.) Recipient age: 1 2 Donor age: 1 2 HLA match: 1 2 HLA-DR match: 1 2 CIT (hrs): 1 2 DGF (days): 1 2 1-yr Serum creatinine (mg/dl): 1 2 5-yr Serum creatinine (mg/dl): 1 2 10-yr Serum creatinine (mg/dl): 1 2 No. rejection episodes: 1 2
Mean ⫾ SD
p Value 0.4
11.504 ⫾ 4.2279 10.414 ⫾ 4.709 0.2 9.93 ⫾ 13.65 19.3 ⫾ 9.26 0.08 0.63 ⫾ 0.576 0.80 ⫾ 0.447 0.55 0.79 ⫾ 0.658 1.20 ⫾ 0.837 0.18 24.6 24.8
⫾ 6.83 ⫾ 1.78 0.32
13.56 ⫾ 9.3 10.67 ⫾ 2.3 0.39 1.12 ⫾ 0.56 1.22 ⫾ 0.65 0.16 1.13 ⫾ 0.47 1.05 ⫾ 0.15 0.73 1.14 ⫾ 0.41 1.11 ⫾ 0.33 0.31 0.6 1.4
⫾ 1.0 ⫾ 0.5
1 and 2 was glomerulonephritis (43% and 41%, p ⫽ 0.8), followed by vesicoureteral reflux (22% and 20%, p ⫽ 0.6) and congenital renal anomalies such as multicystic kidney and posterior urethral valves (15% and 18%, respectively, p ⫽ 0.65). Several immunosuppression schedules were administered during the study period. Regimens containing prednisone plus azathioprine were used from 1978 to 1990. Calcineurin inhibitors were introduced in 1990. Cyclosporine A plus prednisone plus azathioprine was administered from June 1990 to June 1996. From July 1996 to 2006 cyclosporine was replaced by tacrolimus (FK506). Mycophenolate mofetil replaced azathioprine in 2005. In patients undergoing retransplantation and those at high immune risk treatment was induced with monoclonal or polyclonal antibodies. We analyzed the DGF rate, vascular complications, acute rejection episodes and serum creatinine at 1, 5, 10 and 15 years. Differences were estimated using the Student t test. Actuarial graft and patient survival was determined at the same time points using Kaplan-Meier log rank plots. A Cox regression model was developed to estimate the relationship between survival and several independent exploratory variables. Statistical significance was considered at p ⬍0.05.
2583
sity of Wisconsin solution in 52.6% of cases and Euro-Collins solution in 47.4%. No significant differences were observed in donor or receptor age, HLAB/DR match, CIT or DGF duration. Kidneys were implanted in the iliac fossa in 153 cases (91.2%) with vascular anastomosis to the iliac vessels. The transperitoneal approach with vascular anastomosis to the aorta and cava was used when the recipient was younger than 4 years or weighed less than 20 kg and in the 20 (8.8%) who received a third transplant due to extensive fibrosis. Ureteral reimplantation was done using the Paquin technique. Since 2003, the Taguchi 1-stitch technique has been used. The incidence of DGF in first transplant cases was slightly higher than in retransplant cases but this difference was not significant (42.5% vs 35.8%, p ⫽ 0.08). Median CIT in groups 1 and 2 was high with no significant differences, including 27 hours in group 1 vs 24 hours in group 2 (p ⫽ 0.3). The cumulative incidence of acute rejection episodes in group 1 was lower than that of repeat grafts but the difference was not statistically significant (42% vs 46.7%, p ⫽ 0.25). There were no significant differences in graft survival between first transplants and retransplants for all followup periods (log rank p ⫽ 0.757, fig. 1). Allograft half-life survival was 9.05 years (range 7.95 to 10.15) years for the first grafts and 9.07 years (range 6.66 to 11.49) for retransplants. The patient survival rate at 1, 5 and 15 years was 95.8%, 89.6% and 84.9% in group 1, respectively, and 93.6% in group 2 for all periods (p ⫽ 0.25). Calcineurin inhibitor administration improved 1-year and long-term graft survival in each group (log rank p ⫽ 0.02, fig. 2). Graft survival half-life was 8 years (range 6.7 to 9.4) before the introduction of
RESULTS The table lists the characteristics of the 2 groups. Kidneys were placed in cold storage using Univer-
Figure 1. Initial (blue curve) and repeat (green curve) kidney transplant cumulative survival.
2584
CADAVER DONOR KIDNEY RETRANSPLANTATION COMPLICATIONS AND OUTCOME
Figure 2. Kidney graft cumulative survival in patients with (green curves) vs without (blue curves) calcineurin inhibitor. A, initial transplant. B, transplants 2 and 3.
calcineurin inhibitors and 10.3 years (range 8.8 to 10.8) thereafter. The incidence of acute rejection episodes was also significantly lower for first transplants and retransplants when calcineurin inhibitors were used (log rank p ⫽ 0.001). Vascular complications developed in 9 patients (7.5%) in group 1, including arterial thrombosis in 4, venous thrombosis in 3 and renal artery stenos in 2, and in 5 (5.6%) in group 2, including arterial thrombosis in 4 and venous thrombosis in 1 (p ⬎0.05). A total of 65 grafts (54.1%) were lost in group 1 due to immunological reasons in 53 (81.5%) (chronic rejection in 41 and refractory acute rejection in 12), vascular complications in 7 (10.7%) and recurrent renal disease in 5 (7.8%). A total of 22 grafts (41.5%) were lost in group 2 due to immunological reasons in 17 (chronic rejection in 14 and refractory acute rejection in 3) and vascular causes in 5 (9.4%) (p ⫽ 0.03). Of the 30 patients who underwent retransplantation and an immunosuppressive regimen without calcineurin inhibitors the graft was lost in 14 (46%), of whom 9 (64%) experienced refractory rejection with the graft lost in year 1 after transplantation. After the systematic introduction of calcineurin inhibitors the graft was lost in 8 of 23 retransplantation cases (34.7%), including 3 due to nonadherence, 1 due to nephropathy relapse and 4 due to refractory rejection. Only 3 of these grafts (37.5%) lost function during year 1 after transplantation. A significant difference was observed in the total retransplant graft loss rate before vs after the introduction of calcineurin inhibitors (46% vs 34.7%, p ⫽ 0.04).
DISCUSSION KT is the treatment of choice in children with ESRD.1 Advances in immunosuppression and improvements in surgical techniques in children have resulted in improved outcomes. The success of this
approach has created a demand for the operation. We report the long-term outcome of 173 cadaver donor KTs in a pediatric population. We compared the effects of initial transplantation with those of retransplantation. The main cause of renal insufficiency in our series was glomerular disease, followed by abnormalities with no differences between the groups. García et al reported that in infants and young children congenital conditions and renal dysplasia lead to renal failure but in older children acquired renal disease (glomerulonephritis) leads to renal failure.2 In our groups no significant differences were observed in graft outcome, or in patient or graft survival according to the cause of ESRD. CIT was more than 24 hours in each group, which may explain the significant rate of delayed graft failure. Others also reported the negative effect of CIT and an evident detrimental effect on initial graft function, especially when it lasts more than 24 hours.3 van Lieburg et al reported a high (12%) incidence of vascular complications in pediatric recipients.4 A possible explanation is the combination of young age and low body weight in recipients, and the young age of donors as well as the high preoperative urine production. Children with hypoplastic or dysplastic kidneys are at greater risk for thrombosis. It may be possible to prevent thrombosis by administering albumin and fluids. We did not take any special measures other than applying a meticulous surgical technique. None of our patients received pharmacological prophylaxis for thrombosis. Regarding functional outcome, in a long-term study of pediatric kidney transplant recipients Schurman and McEnery reported 62% graft survival at 1 year and a 60% rate for retransplants with no significant effect of calcineurin inhibitors on long-term kidney graft survival.5 Shapiro and Sarwal reported a global rate of 1-year kidney graft survival in pediatric first transplant recipi-
CADAVER DONOR KIDNEY RETRANSPLANTATION COMPLICATIONS AND OUTCOME
ents of 93% for living donor organs and 77% for cadaver donor organs.6 Ferraresso et al reported an 86% 15-year graft survival rate in 36 first kidney transplant recipients treated with cyclosporine.7 Our 1-year cadaver graft survival rates were higher for first transplants and retransplants (78.7% and 82.8%, respectively). We did not observe significant differences in the long-term functional outcome (p ⫽ 0.757). A higher incidence of acute and chronic rejection is recognized in most series of pediatric kidney recipients.2 This could be due to a more vigorous immune response to the graft, which is hard to control using immunosuppressive regimens that systematically include monoclonal and polyclonal antibodies, calcineurin inhibitors (tacrolimus) and mycophenolate mofetil. These patients commonly have a high number of reactive antibodies, which explains why rejection is the most common cause of graft loss in pediatric recipients.2 The introduction of calcineurin inhibitors in our pediatric KT program in 1990 significantly improved 1-year graft survival for first transplants and retransplants (p ⫽ 0.02). As observed previously,8 the incidence of acute rejection was considerably decreased in patients who received calcineurin inhibitors for initial and repeat KT (p ⫽ 0.001). Cyclosporine and tacrolimus share the same pharmacodynamic property of activated T-cell suppression via calcineurin inhibition and they lead to a considerably improved outcome. Another interesting approach is the replacement of azathioprine by alternatives such as mycophenolate mofetil,9 as in our program. Cyclosporine is being successfully replaced by tacrolimus.10 Also, administering pro-
2585
phylactic basiliximab in pediatric kidney transplant recipients has significantly decreased the occurrence of acute rejection episodes.11 Routine pretransplant induction with monoclonal antibodies, polyclonal antibodies and thymoglobulin has decreased the incidence of acute rejection and increased graft tolerance. It is well known that longterm graft survival is associated with a lower incidence of acute rejection.12 Overall survival rates at 1, 2 and 5 years were reported to be 98%, 97% and 95% in living donor recipients, and 97%, 95% and 92% in recipients of cadaver organs.3 In our series the patient survival rate at 1, 5 and 15 years was 95.8%, 89.6% and 84.9% in group 1, respectively, and 93.6% in group 2 for all 3 periods (p ⫽ 0.25). Poor adherence to treatment is a reason why transplants in adolescents and young adults can show lower midterm and long-term survival.13,14 Adaptation to the situation of the patient in this subgroup can be complex and requires special care by the pediatric nephrologist. We recorded 3 cases of loss of a second graft due to nonadherence, representing 16.6% of the total number of lost second transplants.
CONCLUSIONS We report a 28-year experience with cadaveric donor KT in pediatric patients. We found no differences in long-term graft survival between first transplants and retransplants. Nonetheless, the impact of immunosuppressive agents (calcineurin inhibitors) was highly significant with better midterm and long-term results in first transplant and retransplant cases.
REFERENCES 1. Salvatierra O Jr: Pediatric renal transplantation. Transplant Proc 1999; 31: 1782.
6. Shapiro R and Sarwal MM: Pediatric kidney transplantation. Pediatr Clin N Am 2010; 57: 393.
2. García CD, Bittencourt VB, Tumelero A et al: 300 Pediatric renal transplantations: a single-center experience. Transplant Proc 2006; 38: 3454.
7. Ferraresso M, Ghio L, Raiteri L et al: Pediatric kidney transplantation: a snapshot 10 years later. Transplant Proc 2008; 40: 1852.
3. Al-Akash SI and Ettenger RB: Trasplante de riñón en niños. In: Trasplante Renal. Edited by GM Danovitch. Marbán, Spain: Lippincott Williams & Wilkins 2002.
8. Kapturczak MH, Meier-Kriesche HU and Kaplan B: Pharmacology of calcineurin antagonists. Transplant Proc, suppl., 2004; 36: 25S.
12. Parada B, Figuereido A, Nunes P et al: Pediatric renal transplantation: comparative study with renal transplantation in the adult population. Transplant Proc 2005; 37: 2771.
4. van Lieburg AF, de Jong MC, Hoitsma AJ et al: Renal transplant thrombosis in children. J Pediatr Surg 1995; 30: 615.
9. Otukesh H and Sharifian M: Mycophenolate mofetil in pediatric kidney transplants. Transplant Proc 2005; 37: 3012.
13. Giessing M, Muller D, Winkelmann B et al: Kidney transplantation in children and adolescents. Transplant Proc 2007; 39: 2197.
5. Schurman SJ and McEnery PT: Factors influencing short-term and long-term pediatric renal transplant survival. J Pediatr 1997; 130: 455.
10. Morales JM and Andrés A: Ten years of treatment with tacrolimus. Transplant Proc 2005; 37: 3738.
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