Search

Editorial. Comments on the ethical and moral issues which practitioners and the pediatric community must address about the transplantation of organ in infants and infants who became organ donors. Discussion on the beginning and ending of life; Human organs that are commonly needed in infant transplantation.

Pediatric heart transplant patients at our institution are immunosuppressed with a CNI and another immune-modulating agent without utilizing corticosteroids. Patients whose renal function worsened and who did not respond to CNI minimization had their CNI discontinued. The clinical history of 35 pediatric heart transplant patients with significant renal insufficiency whose CNI was discontinued was retrospectively analyzed. Data including serum creatinine and weight were collected before, at time of, and every 3-6 months after CNI discontinuation. This was used to calculate an eGFR. Cardiac allograft rejection and mortality data were also collected. CNI discontinuation occurred 39 times in 35 patients. The median eGFR significantly increased by 14 mL/min 3 months after CNI discontinuation and the increase continued to be significant ( P≤.05) at 5 years. Freedom from rejection analysis showed no difference between graft rejection 2 years before versus after CNI discontinuation ( P=.437). No mortality was associated with CNI discontinuation. Immunosuppression free of CNIs and corticosteroids appears to be a safe alternative in pediatric heart transplant patients with significant renal insufficiency. Furthermore, this strategy can significantly reverse renal insufficiency, even late after transplantation. [ABSTRACT FROM AUTHOR]

Background: Late infections are common causes of morbidity and mortality after pediatric heart transplantation. In this multicenter study from 6 centers, we investigated the association between genetic polymorphisms (GPs) in immune response genes and late post-transplantation infections in 524 patients. Methods: Late infection was defined as a clinical infectious process occurring >60 days after transplantation and requiring hospitalization, intravenous antimicrobial therapy, or a life-threatening infection requiring oral therapy. All patients provided a blood sample for GP analyses of 18 GPs in cytokine, growth factor, and effector molecule genes by single specific primer-polymerase chain reaction and/or sequencing. Significant associations in univariable analyses were tested in multivariable Cox regression models. Results: Late infection was common, with 48.7% of patients experiencing ≥1 late infection, 25.2% had ≥1 late bacterial infection, and 30.5% had ≥1 late viral infection. Older age at transplantation was a protective factor for late infection, both bacterial and viral (hazard ratio [HR] 0.89–0.92 per 1-year age increase, p < 0.001). Adjusting for age, race, and transplant etiology, late bacterial infection was associated with HMOX1 A+326G AG and GG genotypes (HR, 2.41, 95% confidence interval [CI] 1.35–4.30; p = 0.003) and GZMB A-295G AA genotype (HR, 1.47; 95% CI; 1.03–2.1; p = 0.036). Late viral infection was associated with FAS A-670G GG genotype (HR, 1.42; 95% CI, 1.00–2.00; p = 0.050) in the adjusted model and with CTLA4 A+49G AA and AG genotypes (HR, 1.49; 95% CI, 1.02–2.19; p = 0.041) in univariable analysis. Conclusion: We found an association between late bacterial infection and GP of HMOX1, which may control macrophage activation. A weaker association was also found between late viral infection and GP of CTLA4, a regulator of T-cell activation. This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation. [Copyright &y& Elsevier]

Background: The survival of recipients of cardiac allografts is limited by rejection and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss. Methods: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence of virus by the polymerase chain reaction (PCR). Results: PCR analyses were performed on 553 consecutive biopsy samples from 149 transplant recipients. Viral genome was amplified from 48 samples (8.7 percent) from 34 patients (23 percent); adenovirus was found in 30 samples, enterovirus in 9 samples, parvovirus in 5 samples, cytomegalovirus in 2 samples, herpes simplex virus in 1 sample, and Epstein–Barr virus in 1 sample. In 29 of the 34 patients with positive results on PCR (85 percent), an adverse cardiac event occurred within three months after the positive biopsy, and 9 of the 34 patients had graft loss due to coronary vasculopathy, chronic graft failure, or acute rejection. In 39 of the 115 patients with negative results on PCR (34 percent), an adverse cardiac event occurred within three months of the negative PCR finding; graft loss did not occur in any of the patients in this group. The odds of graft loss were 6.5 times as great among those with positive results on PCR (P=0.006). The detection of adenovirus was associated with considerably reduced graft survival (P=0.002). Conclusions: Identification of viral genome, particularly adenovirus, in the myocardium of pediatric transplant recipients is predictive of adverse clinical events, including coronary vasculopathy and graft loss. (N Engl J Med 2001;344:1498-503.) [ABSTRACT FROM AUTHOR]

This review details the indications for heart transplantation in children. Contraindications have evolved from absolute to relative. Controversial issues remain and this paper represents a consensus of more than a dozen centers that have programs that remain active performing pediatric heart transplants. [ABSTRACT FROM AUTHOR]