Pediatric renal transplantation

This article outlines the current status of pediatric renal transplantation and emphasizes a practical approach to patient management. It discusses two areas of renal transplantation in children in which results differ significantly between children and adults. These areas are renal transplantation in the very young child and transplantation in children with renal failure secondary to urologic disease.     

Pediatric renal transplantation

Summary The past 20 years of experience with pediatric renal transplantation have shown that it has a very important therapeutic role. Significant advances in reducing costs and improving results will need to be accomplished in the future.     

Pediatric cadaver kidneys. Their use in renal transplantation.

Of 350 consecutive cadaver kidney transplants, 32 kidneys from donors aged 1 day to 9 years were transplanted. Our results indicate that, with strict adherence to certain guidelines in kidney procurement and transplantion, pediatric kidneys are excellent donor graft material. In contrast to en bloc transplantation of both kidneys from pediatric donors, each donor can provide kidneys for two recipients. In addition, the transplantation of pediatric kidneys as single units is both simple and safe.     

Pediatric renal transplantation in Laurence-Moon-Biedl syndrome

Two cases of renal transplantation in pediatric patients with Laurence-Moon-Biedl syndrome are reported. Immunosuppressive therapy consisted of cyclosporine, prednisone and azathioprine. Renal function has been good but both patients developed morbid obesity.     

Pediatric renal transplantation under FK-506 immunosuppression.

Renal transplantation (11 cadaveric and 1 living-related donor) was performed in 12 pediatric recipients (mean age 10.8 years) under FK-506 immunosuppression in combination with prednisone therapy. At a mean followup of 6.1 months, patient and graft survival rates were 100% and 92%, respectively. The only graft loss was due to the recurrent hemolytic uremic syndrome 4 days after transplantation. In the functioning grafts the mean serum creatinine is 1.59 +/- 1.27 mg./dl. and the mean blood urea nitrogen is 36.3 +/- 24.6 mg./dl. Three patients take no prednisone, 5 are receiving 0.15 to 0.25 mg./kg. per day and 3 are taking 0.35 to 0.5 mg./kg. per day. There was a total of 8 rejection episodes in 5 patients. All rejection episodes were successfully reversed. Complications of transplantation included an episode of seizures in 1 patient, cytomegalovirus infection in 1 and steroid-induced diabetes mellitus in 1. Since pediatric transplant recipients are a group in whom the reduction or elimination of steroids is highly desirable, FK-506 immunosuppression may be particularly suited for use in this population.     

Pediatric renal transplantation without steroids

Pediatric renal transplant patients present a number of challenges and problems, especially the inhibited post-transplant growth seen in children receiving standard immunosuppressive triple therapy that includes steroids. We report the successful use of steroid-free immunosuppression since 1990 in 14 pediatric renal allograft recipients who received a 10-day initial course of antilymphocyte globulin and surface area-adjusted doses of cyclosporine, 7 of whom also received mycophenolate mofetil (MMF) as maintenance immunosuppression. Only 1 patient died (3 months after transplantation as a result of a primary Epstein-Barr virus infection-induced lymphoproliferative disorder), 1 patient’s graft never functioned, and another patient lost his graft after 3 years because of chronic rejection. Three patients experienced early acute cellular rejection, which resolved in 2 cases with OKT3, and in the 3rd with MMF. There were no late acute rejections. All patients evidenced growth and a growth spurt under this regimen. We conclude that all the pediatric patients benefited from our steroid-free protocol and that this protocol is superior to conventional triple therapies, which entail the eventual reduction and discontinuation of steroids, a procedure that not only inhibits growth but also carries an additional risk of acute rejection due to a steroid-adapted immune response. Received April 16, 1997; received in revised form September 8, 1997; accepted September 10, 1997     

Outcomes of pediatric renal transplantation in France

Significant progress has been observed in pediatric renal transplantation over the last 20 years, leading to an increase in graft and patient survival. Mortality is low and is mainly due to infections, neoplasias and complications related to the initial disease. Graft survival is 67% at 10 years. Factors which influence graft survival are: donor type (results are better with a live donor), donor age, recipient age (with 2 periods at risk:<2 years old and teenagers), HLA incompatibilities, and recurrence of the initial disease. Chronic allograft nephropathy (CAN) is the major cause of late graft loss. Poor compliance, especially in teenagers, may lead to late rejections and graft loss. Calcineurin inhibitors nephrotoxicity is in part responsible for the development of CAN, thus treatments and the role of mTOR inhibitors will probably evolve. These different factors are discussed in this article.     

Pediatric renal transplantation under tacrolimus-based immunosuppression

BACKGROUND: Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6+/-5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3+/-14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5+/-8.8 hr. The mean number of HLA matches and mismatches was 2.8+/-1.2 and 2.9+/-1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0+/-0.2 years. RESULTS: The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1+/-0.5 mg/dl, and the corresponding calculated creatinine clearance was 88+/-25 ml/min/1.73 m2. A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were -2.3+/-2.0, -1.7+/-1.0, and +0.36+/-1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. CONCLUSIONS: These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti-hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD.     

Pediatric renal transplantation: comparative study with renal transplantation in the adult population

PURPOSE: To retrospectively review our experience with pediatric renal transplantation and to compare the results with the adult population. PATIENTS AND METHODS: Between January 1981 and August 2003, 74 renal transplants were performed in patients < or =18 years at the time of the transplant--the pediatric group versus 1153 patients in the adult group. We analyzed various risk factors for actuarial kidney graft and patient survivals using the Kaplan-Meier method. RESULTS: Median ages were 13.8 +/- 3.5 and 42.6 +/- 2.4 years, respectively. There was no statistically significant difference in the human leukocyte antigen matching or immunosuppression. There was, however, a younger donor age and shorter ischemia time in the pediatric group. Overall, kidney transplant survival rates for patients < or =18 years at 1, 2, 5, and 10 years were 94.4%, 91.3%, 70.6%, and 58.2%, respectively, with no significant difference for patients older than 18 (91.2%, 89.3%, 78.8%, 60.5%, P = .4325). There was a significantly decreased graft survival in the adult group at 10 years when the donor age was over 60 years and when the ischemia time was > or =20 hours. The incidence of delayed graft function and the creatinine levels of functioning grafts did not differ between the two groups. During the follow-up, acute rejections were more frequent in the younger group. Patient survival in the pediatric group at 1, 2, 5, and 10 years was 98.6%, 98.8%, 98.6%, and 90.3%, respectively, significantly lower in the adult group (95.3%, 94.0%, 87.9%, 76.8%, P < .02). CONCLUSIONS: Renal transplantation may be successfully performed in the pediatric patients with end-stage renal disease. Overall graft survival at 10 years did not differ significantly between the two groups. There is a higher incidence of acute rejections but longer patient survival in the pediatric population.     

Pediatric renal transplantation: a single-center experience

A retrospective analysis was performed on 33 pediatric renal transplants performed over last 8 years. The mean age and weight at the time of transplantation was 12.5 +/- 3.86 years and 28.75 +/- 9.04 kg, respectively. Twenty-six children were boys and 7 were girls. Thirteen children had underlying glomerular disease and 17 had tubulointerstitial disease. All transplants were living related except two, which were from deceased donors. The median duration of hemodialysis and peritoneal dialysis before transplantation were 2.75 and 4 months, respectively. The most common posttransplant complication was urinary tract infection. Immunosuppression medications in the majority included cyclosporine, azathioprine, and corticosteroids. Actuarial graft survivals at 1, 3, and 5 years were 94%, 90%, and 82%, respectively.     

Pediatric renal transplantation from related living donor

Living related donor (LRD) provides significant advantages when compared with cadaveric donor (CAD) in term of improved patient and graft survival and shorten waiting time. From 1985, 176 kidney transplants were performed at our Center. Of these, 156 (89%) were from CAD and 20 (11%) were from LRD, first degree. The purpose of this paper is to show our experience at 5 years with use of LRD. All donors underwent standardized metabolic workup, angiography assessed and renal function test. Twelve children received their first transplant and 8 were retransplant (6-second, 1-third and 1-fourth). Immunosuppressive therapy consisted of globulin antithymocyte, azathioprine, cyclosporine and prednisolone, using FK506 and mycophenolate mofetil in some of them. Four kidneys with multiple renal arteries were reconstructed ex vivo with microsurgical technique before transplantation. The most significant morbidity was due to FK506-associated thrombotic microangiopathy (TMA) with graft lost. All patients (donor and recipient) survived. Five years graft survival rate is 95% and mean glomerular filtration rate is 81.33 ml/min/1.73 m2.     

Pediatric renal transplantation and the dysfunctional bladder

We retrospectively reviewed our long-term experience with pediatric renal transplantation into a dysfunctional lower urinary tract to evaluate graft survival, function, and special urological complications. Between 1967 and March 2000, a total of 349 renal transplantations were performed in children younger than 18 years. Malformations of the lower urinary tract were the reasons for end-stage renal failure in 66 children (18.6%). The cause of urinary tract disorders included: meningomyelocele connected with neuropathic bladder (n=4 transplantations); prune belly syndrome (n=5 transplantations); VATER association (n=2 transplantations); posterior urethral valves (n=27 transplantations); and vesico-uretero-renal reflux (n=28 transplantations). The majority of the patients underwent surgical interventions to preserve renal function or to prepare renal transplantation. The 1- and 5-year graft survival rate was evaluated with special reference to the underlying disease. The 1-year graft survival rate in all children with lower urinary tract malformations was 83.3%, compared with 88% for all children. In those children with vesico-ureteral reflux, it was 92.8% and in the children with Vater association and prune belly syndrome, it was 85.7%. One graft was lost in the children who had neurogenic bladder, so the 1-year graft survival rate was 75%. The worst 1-year graft survival rate was obtained for boys who had posterior urethral valves (1-year graft survival rate: 74%; 5-year graft survival rate: 62.9%). Concerning the 5-year graft survival rate, it was 70% for all children with malformations of the urinary tract. The best rate was obtained for children with reflux in the native kidneys (78.5%), followed by those with VATER association and prune belly syndrome. As an additional child with neurogenic bladder lost his graft, the 5-year graft survival rate was 50%. Pediatric renal transplantation into a dysfunctional bladder can be connected with high urological complication rates which may contribute to worse graft survival. The 1- and 5-year graft survival rate in children with malformations of the lower urinary tract is worse than in children without bladder dysfunction. We regarded a striking difference between graft survival and the urological disorders which led to renal insufficiency. We obtained the worst graft survival rates in children with posterior urethral valves which are usually connected with bladder emptying problems and dysfunctional voiding. Potential pediatric transplant recipients must be classified according to pathophysiological as well as anatomical abnormalities of the urinary tract and all urological problems have to be solved prior to transplantation. At our center, living donors are favored to plan transplantation of these children properly.