Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is an important complication of transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database has documented 56 cases of PTLD, the largest such series to date. METHODS: We analyzed the available longitudinal and multicenter data in the NAPRTCS database to evaluate the demographic and therapeutic risk factors and the temporal trends for PTLD in children after renal transplantation. RESULTS: The overall incidence of PTLD was 1.2% of all patients or 298/100,000 posttransplantation years of follow-up. However, this incidence increased from 254/100,000 years between 1987 and 1991 to 395/100,000 years from 1992 onwards. In the same periods, the time to PTLD decreased from a median of 356 days (range 843048) to a median of 190 days (range 42-944). PTLD occurred with greater frequency in white children (P=0.003) and in cadaver donor transplants (P=0.019), but there was no significant predilection for gender, younger children (0-5 years), or primary diagnosis. No significant difference was found in the use of anti-T-cell antibodies or in doses of CsA, azathioprine, or prednisone at 1 month, 6 months, and 1 year. Between 1996 and 1997, 69 patients were initiated with tacrolimus. Eight cases of PTLD were identified in these recipients to date (prevalence rate 11.5%), compared with 46/4084 (1.1%) where cyclosporine was used (P<0.0001). CONCLUSIONS: There is a trend towards increasing incidence and earlier occurrence of PTLD in the pediatric renal transplant population. White race and cadaver donor sources are risk factors not reported before. Continued monitoring of tacrolimus immunosuppression is important.

Predictive factors for delayed graft function (DGF) and its impact on renal graft survival in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

We define delayed graft function (DGF) as the need for dialysis during the first post-transplant week. We analyzed 5272 transplants, of which 2486 were of living donor (LD) and 2786 were of cadaver donor (CD) origin. Twelve per cent (620/5272) of all patients developed DGF. Donor specific rates were 5.6% for LD and 19.1% for CD patients. Factors predictive of DGF in CD patients were: African-American race (25%), prolonged cold ischemia (24%), absence of T-cell induction antibody therapy and absence of HLA-DR matching. The relative risk (RR) for graft failure due to DGF was 6.02 (p < 0.001) in LD patients and 2.58 (p < 0.001) for CD recipients. Two-year graft survival (GS) in LD patients without DGF was 89.6%, compared to 41.6% for those with DGF (p < 0.001); in CD patients it was 80.2% and 49.5%, respectively (p < 0.001). Censoring for primary non-function, GS for LD patients with a functioning graft at 30 d post-transplant and no DGF was 91.5%, compared to 70.1% for those with DGF (p < 0.001); GS for CD patients was 83.8% and 68.7%, respectively (p < 0.001). However, when patients whose grafts had failed during the first year were censored no differences in GS were noted between patients with and without DGF for either LD or CD recipients. To determine whether DGF acts as an independent risk factor for graft failure, patients were segregated into four groups: rejection with DGF; rejection without DGF; DGF without rejection; and no DGF, no rejection. When these groups were compared DGF emerged as an independent risk factor for graft failure. This large study reviewing pediatric renal transplantation over 10 yr clearly delineates the role of DGF as a major risk factor for graft failure.

The impact of donor source, recipient age, pre-operative immunotherapy and induction therapy on early and late acute rejections in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Acute rejection is a frequent event in pediatric transplantation. In addition to graft loss, acute rejection episodes stimulate the development of chronic rejection and inhibit growth in children post-transplantation. In this study, we analyzed our data from 1987 through 1996 to identify acute rejection episodes in children. In 2,520 living donor (LD) transplants there were 2,540 rejection episodes (rejection ratio: 1.1), and in 2,579 cadaver donor (CD) transplants 3,653 episodes were observed (rejection ratio: 1.32). For LD recipients the first rejection occurred sooner when there was at least one HLA-DR mismatch (RR=1.6, p<0.001) and prophylactic T-cell antibody was not used (RR=1.4, p<0.001). For CD transplants absence of prophylactic T-cell antibody (RR=1.2, p<0.001) and donor age below five years were risk factors (RR=1.5, p<0.001). Late initial acute rejections were seen in 327 of 1,471 patients (22.2%) who were rejection free at one year. At risk for the development of late rejections were children over the age of six years at transplantation (RR=1.7, p<0.001) and children of non-white origin (RR=1.5, p <0.002). For LD transplant recipients in the age range of 0-5 years, irreversible rejection was observed in 8.7% compared to 4.1% for older children (RR=1.46, p<0.001). Similar results for CD transplants were 12.6% versus 6.6% (RR=1.5, p<0.00). The high frequency of rejection episodes in children and the greater irreversibility in younger children suggest pediatric patients may have a more robust immune response. Current ongoing studies in the molecular mechanisms of the pathogenesis of rejection in surveillance biopsies of children may help determine if this hypothesis is valid.

Pediatric renal transplantation--the NAPRTCS experience.

The NAPRTCS has enrolled 4,329 children who have received an index renal transplant since 1987. Seventy-three percent of the transplant recipients were children above 6 years of age. In the age group below 6 years rejection episodes are not more frequent, however the first acute rejection episode is frequently irreversible leading to graft failure. Many of the renal disorders that lead to ESRD and transplantation in adults, such as diabetes and hypertension, are less often observed in the pediatric population. Developmental disorders, such as renal dysplasia and obstructive uropathy, are frequent diagnostic entities, and the most common glomerular disorder leading to transplantation in children is focal segmental glomerulosclerosis. In an attempt to overcome dialysis-associated growth retardation many pediatric renal centers resort to preemptive transplantation, thus 24% of the children receiving a transplant have never undergone dialysis. Graft survival in these children is similar to that observed in children receiving maintenance dialysis, however accelerated growth is not noted. Catch-up growth, defined as gain of 1 SDS, is observed in 47% of children below the age of 6 years and in only 22% of children over the age of 6 years. Infants (below 2 years) have a higher mortality rate following transplantation compared to older children. Long-term (5-year) graft survival for children receiving a cadaver donor graft is 60%, and for living donor kidney recipients the graft survival is 76%. Due to changes in practice patterns, such as a judicious use of cadaver donors, increased use of prophylactic T-cell antibody, and better maintenance immunosuppression, cadaver donor graft survival has improved each year since 1987. The cohorts of children with a cadaver donor transplant in the years 1991 and 1992 have a 2-year graft survival which is 10% better than that observed in the earlier years.

CT appearance of large sternoclavicular calcific masses in a teenager with chronic renal disease and secondary hyperparathyroidism, on hemodialysis maintenance.

The case of a 14-year-old teenager is reported who had large sternoclavicular masses. The young man had chronic renal disease due to chronic glomerulonephritis and had been on hemodialysis maintenance for many years. CT showed the masses to be lobulated with low attenuation septa. Metastatic calcification occurs in various systemic diseases.