Potential Pediatric Transplant Research Articles

Donor selection in pediatric kidney transplantation using DR and DQ eplet mismatching: A new histocompatibility paradigm.

It is now appreciated that more HLA-DR mismatching at the time of the first renal transplant is associated with higher degrees of sensitization, lower rates and longer times to retransplantation, and worse graft outcomes in children who are subsequently retransplanted. As such, our pediatric renal transplant program preferentially uses 0 or 1 HLA-DR-mismatched kidneys and reserves 2 DR-mismatched kidneys for recipients with an eminent need for a kidney. Based on a new HLA class II epitope matching strategy that is designed to minimize dnDSA production to DR and DQ antigens, we evaluated the prevalence of DR and DQ eplet mismatching for dd offers made to our pediatric wait-listed candidates. Each candidate/dd pair were HLA-DR (β1 and β3 and/or β5) and DQ (α1 and β1) allele typed by rSSO and were then evaluated for eplet mismatches by the HLAMatchmaker program. We evaluated 78 offers made to 16 children on our UNOS waiting list from 27 consecutive dd from 4/14/14 to 3/23/15. The data show that 40% (8/20) of the 1 DR-mismatched dd offers and 64% (37/58) of the 2 DR-mismatched offers were in the high-risk category for both DR and DQ dnDSA development. Whereas only 15% (3/20) of the 1 DR-mismatched offers and 5% (3/58) of the 2 DR-mismatched offers were in the low-risk category for both DR and DQ dnDSA development, 55% and 33% of the 1 DR- and 2 DR-mismatched offers, respectively, had a favorable DQ eplet mismatch threshold. In summary, HLA class II eplet mismatching is common in potential pediatric transplant recipient/donor pairs. Additional study will be necessary to validate the DR and DQ eplet threshold levels in children and to determine whether eplet mismatching strategies in donor selection result in improved transplant outcome and decreased dnDSA production.

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.