- Email: [email protected]
Pediatric Renal Transplantation: A Single Center Experience
Pediatric Renal Transplantation: A Single Center Experience A. Kavaz, Z.B. Özçakar, B. Bulum, A. Tüzüner, K. Keven, S¸. S¸engül, M. Ekim, and F. Yalçınkaya ABSTRACT Renal transplantation is the treatment of choice for children with end-stage renal disease. The aim of this study was to evaluate retrospectively of our 37 pediatric renal allograft recipients, including 20 boys and 17 girls from July 2007 to August 2012. The overall mean age at transplantation was 12.16 ⫾ 4.25 years. Three patients (8.1%) were transplanted preemptively; two were ABO-incompatible transplantations. The majority of recipients received living donor grafts (81%). The mean duration of follow-up was 25.10 ⫾ 14.95 months. Seven acute rejection episodes were observed in 6 patients (16.2%). Eleven recipients developed serious viral infections: cytomegalovirus (n ⫽ 8), parvovirus (n ⫽ 2), BK virus (polyoma hominis 1) (n ⫽ 2), or Ebstein-Barr virus (n ⫽ 1). Three patients died; one from posttransplant lymphoproliferative disease, one from primary disease recurrence with infection, and one from sepsis. In conclusion, kidney transplantation is the treatment of choice for end-stage renal disease. Infection was the major concern after this procedure. ENAL transplantation is the treatment of choice for children with end-stage renal disease (ESRD) offering advantages of improved survival, growth potential, cognitive development, and quality of life.1 The aim of this study was to evaluate pediatric renal allograft recipients in our center.
R
METHODS We retrospectively evaluated the 37 pediatric renal transplantations performed in our center between July 2007 and August 2012 for demographic profiles, donor details, immunosuppression, posttransplant complications, and outcomes. The standard immunsuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and prednisolone. Nine patients received basiliximab induction therapy for cadaveric transplantation (n ⫽ 7) or ABO-incompatible cases (n ⫽ 2). Two ABO-incompatible recepients received a single dose of rituximab (375 mg/m2). Depending on the level of anti-A/B antibodies, plasma exchanges were performed before transplantation. Antiviral, antifungal, and antipneumocystis carinii prophylaxis were prescribed for all renal transplant recipients. The diagnosis of an acute rejection episode was based on clinical features of an abrupt increase in serum creatinine concentration; a renal biopsy was performed for confirmation in all cases. The rejection episodes were treated with 3 daily pulses of intravenous methylprednisolone. The data are expressed as mean values ⫾ standard deviations. Analyses were performed using The Statistical Package for Social Sciences (SPSS version 19.0, Calif).
RESULTS
Demographic and clinical features of the patients are presented in Table 1. Their mean age at the time of transplantation was © 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 45, 917–918 (2013)
12.16 ⫾ 4.25 years (range, 2.16 to 22 year). There were 20 boys and 17 girls. The etiologies of end-stage renal disease are shown in Table 2. Juvenile nephronopthisis was the most common etiology. Twenty-five patients were on continous ambulatory peritoneal dialysis before transplantation. Preemptive transplantation was performed in 3 patients (8.1%). The majority of cases were grafts from living donors (81%); it was the mother 22/30 living-related renal tranplantations. Two patients received kidneys from ABO-incompatible donors. Seven acute rejection episodes were diagnosed in 6 patients (16.2%), including 6 instances of acute cellular rejection. The rejection episodes, all of which were completely reversible occured at 10.1 ⫾ 7.3 months (range, 3 to 24 months) after transplantation. Three surgical complications were diagnosed in 37 recipients (8.1%): 2 vascular and 1 lymphocele. One patient sufferring from oxalosis displayed disease recurrence at 4 months posttransplantation. Eleven recipients developed 13 serious viral infections: cytomegalovirus (n ⫽ 8), parvovirus (n ⫽ 2), BK virus (polyoma hominis 1) (n ⫽ 2), and Ebstein-Barr virus (n ⫽ 1).
From the Department of Pediatric Nephrology (A.K., Z.B.Ö., B.B., M.E., F.Y.), the Department of Surgery (A.T.), and the Deparment of Nephrology (K.K., S¸.S¸.), Ankara University School of Medicine, Ankara, Turkey. Address reprint requests to Dr. Fatos¸ Yalçınkaya, Çinar Sitesi 5, Blok No:62, U¨mitköy 06530 Ankara, Turkey. E-mail: [email protected] 0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2013.02.081 917
918
KAVAZ, ÖZÇAKAR, BULUM ET AL
The mean follow-up duration was 25.10 ⫾ 14.95 months (range, 1 to 53 months). Three patients died at 5, 20, and 26 months after transplantation, respectively, because of lymphoproliferative disease, primary disease recurrence with infection, and sepsis, respectively. At the last follow-up 34 patients displayed normal graft function. DISCUSSION
Pediatric kidney transplantation is widely recognized to be the treatment of choice for children with ESRD. According to The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry, the most common cause of ESRD was aplastic/hypoplastic/dysplastic kidneys (15.9%).2 Interestingly, our data showed the most common causes of ESRD among pediatric renal transplant recipients at our center was juvenile nephronophitisis (29.7%) or congenital abnormalities of the kidney and urinary tract. The majority of our patients received grafts from living donors (81.1%), a result in accordance with other studies. In general, living donors have been more frequent among pediatric versus adults kidney transplantations.3,4 In addition the waiting period for cadaveric donor transplantation is also long in our country. Preemptive transplantation is an important modality for children. The NAPRTCS registry reported that 24.6% of the patients underwent preemptive transplantations,2 which in our center accounted for 18.1% of our recipients. Two patients received kidneys from ABO-incompatible donors. The transplantations were performed using plasmapheresis and rituximab infusion. Their graft survival outcomes were similar to ABO-compatible donors. Our analysis revealed that seven acute rejection episodes in 6 patients (16.2%) including six acute cellular responses. According to the NAPRTCS 2006 data, 46.7% of renal transplant recipients experience a rejection episode. With the present use of potent immunsuppressive agents their occurrence decreased over time. All of the episodes were treated succesfully. Table 1. Patients Characteristics (n ⴝ 37) Characteristic
Gender Male, n (%) Female, n (%) Age at transplantation, y (mean ⫾ SD) Donor Mother, n (%) Father, n (%) Cadaveric, n (%) Modality of dialysis before transplantation (n ⫽ 34) Hemodialysis, n (%) CAPD, n (%) Preemptive transplant, n (%) Duration of follow-up, m (mean ⫾ SD) Patients with rejections, n (%) One rejection episode Two rejection episodes
Table 2. Underlying Disease Disease
Tubulointerstitial disease (n ⫽ 27) Juvenile nephronopthisis Neurogenic bladder with VUR Hypodysplasia PUV Polycystic kidney disease Reflux nephropathy Oxalosis Prune Belly syndrome Multicystic kidney disease with VUR Cystinosis Glomerular (n ⫽ 8) FSGS FMF, amyloidosis HUS RPGN Unknown (n ⫽ 2)
Finding
11 3 3 2 2 2 1 1 1 1 4 2 1 1
Abbreviations: VUR, vesicoureteral reflux; PUV, posterior urethral valve; FSGS, focal segmental glomerulosclerosis; FMF, familial mediterranean fever; HUS, hemolitic uremic syndrome; RPGN, rapidly progressive glomerulosclerosis.
A significant number of viral infections developed after renal transplantation. Cytomegalovirus (CMV) (21.6%) was the most common viral infection in our center. According to the literature, symptomatic CMV infections occur in 20% to 60% of renal transplant recipients, representing a significant cause of increased morbidity and mortality.5 One of our patients died due to Estein-Barr virus–related posttransplantation lymphoproliferative disease. In recent years Posttransplantation lymphoproliferative disease associated with uncontrolled Ebstein-Barr virus infection has emerged as a significant cause of morbidity and mortality among the pediatric transplant population.6 Recurrence of disease was seen only in the patient with oxalosis. In conclusion, kidney transplantation is the treatment of choice for patients with ESRD. Infection seemed to be the major concern after renal transplantation of our prediatric patients.
Finding
REFERENCES 20 (54) 17 (46) 12.16 ⫾ 4.25 22 (59) 8 (21.6) 7 (18.9) 9 (26.5) 25 (73.5) 3 (8.1) 25.10 ⫾ 14.95 6 (16.2) 5 (83.3) 1 (16.7)
Abbreviation: CAPD, continuous ambulatory peritoneal dialysis.
1. Horslen S, Barr ML, Christiansen LL, et al. Pediatric transplantation in the United States, 1996 –2005. Am J Transplant. 2007;7:1339 –1358. 2. Smith JM, Stablein DM, Munoz R, et al. Contributions of the transplant registry: the 2006 annual report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Pediatr Transplant. 2007;11:366 –373. 3. Harmon WE, McDonald RA, Reyes JD, et al. Pediatric transplantation, 1994 –2003. Am J Transplant. 2005;5:887–903. 4. Magee JC, Krishnan SM, Benfield MR, et al. Pediatric transplantation in the United States, 1997–2006. Am J Transplant. 2008;8:935–945. 5. Cukuranovic J, Ugrenovic S, Jovanovic I, et al. Viral infection in renal transplant recipients. ScientificWorld J. 2012;2012:820621. Epub 2012 May 2. 6. Dharnidharka VR, Sullivian EK, Stablein DM, et al. Risk factors for posttransplant lymphoproliferative disorder in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation. 2001;71:1065–1068.
R
METHODS We retrospectively evaluated the 37 pediatric renal transplantations performed in our center between July 2007 and August 2012 for demographic profiles, donor details, immunosuppression, posttransplant complications, and outcomes. The standard immunsuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and prednisolone. Nine patients received basiliximab induction therapy for cadaveric transplantation (n ⫽ 7) or ABO-incompatible cases (n ⫽ 2). Two ABO-incompatible recepients received a single dose of rituximab (375 mg/m2). Depending on the level of anti-A/B antibodies, plasma exchanges were performed before transplantation. Antiviral, antifungal, and antipneumocystis carinii prophylaxis were prescribed for all renal transplant recipients. The diagnosis of an acute rejection episode was based on clinical features of an abrupt increase in serum creatinine concentration; a renal biopsy was performed for confirmation in all cases. The rejection episodes were treated with 3 daily pulses of intravenous methylprednisolone. The data are expressed as mean values ⫾ standard deviations. Analyses were performed using The Statistical Package for Social Sciences (SPSS version 19.0, Calif).
RESULTS
Demographic and clinical features of the patients are presented in Table 1. Their mean age at the time of transplantation was © 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 45, 917–918 (2013)
12.16 ⫾ 4.25 years (range, 2.16 to 22 year). There were 20 boys and 17 girls. The etiologies of end-stage renal disease are shown in Table 2. Juvenile nephronopthisis was the most common etiology. Twenty-five patients were on continous ambulatory peritoneal dialysis before transplantation. Preemptive transplantation was performed in 3 patients (8.1%). The majority of cases were grafts from living donors (81%); it was the mother 22/30 living-related renal tranplantations. Two patients received kidneys from ABO-incompatible donors. Seven acute rejection episodes were diagnosed in 6 patients (16.2%), including 6 instances of acute cellular rejection. The rejection episodes, all of which were completely reversible occured at 10.1 ⫾ 7.3 months (range, 3 to 24 months) after transplantation. Three surgical complications were diagnosed in 37 recipients (8.1%): 2 vascular and 1 lymphocele. One patient sufferring from oxalosis displayed disease recurrence at 4 months posttransplantation. Eleven recipients developed 13 serious viral infections: cytomegalovirus (n ⫽ 8), parvovirus (n ⫽ 2), BK virus (polyoma hominis 1) (n ⫽ 2), and Ebstein-Barr virus (n ⫽ 1).
From the Department of Pediatric Nephrology (A.K., Z.B.Ö., B.B., M.E., F.Y.), the Department of Surgery (A.T.), and the Deparment of Nephrology (K.K., S¸.S¸.), Ankara University School of Medicine, Ankara, Turkey. Address reprint requests to Dr. Fatos¸ Yalçınkaya, Çinar Sitesi 5, Blok No:62, U¨mitköy 06530 Ankara, Turkey. E-mail: [email protected] 0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2013.02.081 917
918
KAVAZ, ÖZÇAKAR, BULUM ET AL
The mean follow-up duration was 25.10 ⫾ 14.95 months (range, 1 to 53 months). Three patients died at 5, 20, and 26 months after transplantation, respectively, because of lymphoproliferative disease, primary disease recurrence with infection, and sepsis, respectively. At the last follow-up 34 patients displayed normal graft function. DISCUSSION
Pediatric kidney transplantation is widely recognized to be the treatment of choice for children with ESRD. According to The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry, the most common cause of ESRD was aplastic/hypoplastic/dysplastic kidneys (15.9%).2 Interestingly, our data showed the most common causes of ESRD among pediatric renal transplant recipients at our center was juvenile nephronophitisis (29.7%) or congenital abnormalities of the kidney and urinary tract. The majority of our patients received grafts from living donors (81.1%), a result in accordance with other studies. In general, living donors have been more frequent among pediatric versus adults kidney transplantations.3,4 In addition the waiting period for cadaveric donor transplantation is also long in our country. Preemptive transplantation is an important modality for children. The NAPRTCS registry reported that 24.6% of the patients underwent preemptive transplantations,2 which in our center accounted for 18.1% of our recipients. Two patients received kidneys from ABO-incompatible donors. The transplantations were performed using plasmapheresis and rituximab infusion. Their graft survival outcomes were similar to ABO-compatible donors. Our analysis revealed that seven acute rejection episodes in 6 patients (16.2%) including six acute cellular responses. According to the NAPRTCS 2006 data, 46.7% of renal transplant recipients experience a rejection episode. With the present use of potent immunsuppressive agents their occurrence decreased over time. All of the episodes were treated succesfully. Table 1. Patients Characteristics (n ⴝ 37) Characteristic
Gender Male, n (%) Female, n (%) Age at transplantation, y (mean ⫾ SD) Donor Mother, n (%) Father, n (%) Cadaveric, n (%) Modality of dialysis before transplantation (n ⫽ 34) Hemodialysis, n (%) CAPD, n (%) Preemptive transplant, n (%) Duration of follow-up, m (mean ⫾ SD) Patients with rejections, n (%) One rejection episode Two rejection episodes
Table 2. Underlying Disease Disease
Tubulointerstitial disease (n ⫽ 27) Juvenile nephronopthisis Neurogenic bladder with VUR Hypodysplasia PUV Polycystic kidney disease Reflux nephropathy Oxalosis Prune Belly syndrome Multicystic kidney disease with VUR Cystinosis Glomerular (n ⫽ 8) FSGS FMF, amyloidosis HUS RPGN Unknown (n ⫽ 2)
Finding
11 3 3 2 2 2 1 1 1 1 4 2 1 1
Abbreviations: VUR, vesicoureteral reflux; PUV, posterior urethral valve; FSGS, focal segmental glomerulosclerosis; FMF, familial mediterranean fever; HUS, hemolitic uremic syndrome; RPGN, rapidly progressive glomerulosclerosis.
A significant number of viral infections developed after renal transplantation. Cytomegalovirus (CMV) (21.6%) was the most common viral infection in our center. According to the literature, symptomatic CMV infections occur in 20% to 60% of renal transplant recipients, representing a significant cause of increased morbidity and mortality.5 One of our patients died due to Estein-Barr virus–related posttransplantation lymphoproliferative disease. In recent years Posttransplantation lymphoproliferative disease associated with uncontrolled Ebstein-Barr virus infection has emerged as a significant cause of morbidity and mortality among the pediatric transplant population.6 Recurrence of disease was seen only in the patient with oxalosis. In conclusion, kidney transplantation is the treatment of choice for patients with ESRD. Infection seemed to be the major concern after renal transplantation of our prediatric patients.
Finding
REFERENCES 20 (54) 17 (46) 12.16 ⫾ 4.25 22 (59) 8 (21.6) 7 (18.9) 9 (26.5) 25 (73.5) 3 (8.1) 25.10 ⫾ 14.95 6 (16.2) 5 (83.3) 1 (16.7)
Abbreviation: CAPD, continuous ambulatory peritoneal dialysis.
1. Horslen S, Barr ML, Christiansen LL, et al. Pediatric transplantation in the United States, 1996 –2005. Am J Transplant. 2007;7:1339 –1358. 2. Smith JM, Stablein DM, Munoz R, et al. Contributions of the transplant registry: the 2006 annual report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Pediatr Transplant. 2007;11:366 –373. 3. Harmon WE, McDonald RA, Reyes JD, et al. Pediatric transplantation, 1994 –2003. Am J Transplant. 2005;5:887–903. 4. Magee JC, Krishnan SM, Benfield MR, et al. Pediatric transplantation in the United States, 1997–2006. Am J Transplant. 2008;8:935–945. 5. Cukuranovic J, Ugrenovic S, Jovanovic I, et al. Viral infection in renal transplant recipients. ScientificWorld J. 2012;2012:820621. Epub 2012 May 2. 6. Dharnidharka VR, Sullivian EK, Stablein DM, et al. Risk factors for posttransplant lymphoproliferative disorder in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation. 2001;71:1065–1068.