Background Since the earliest clinical successes in solid organ transplantation, the proper method of organ allocation for children has been a contentious subject. Over the past 30–35 years, the medical and social establishments of various countries have favored some degree of preference for children on the respective waiting lists. However, the specific policies to accomplish this have varied widely and changed frequently between organ type and country. Methods Organ allocation policies over time were examined. This review traces the reasons behind and the measures/principles put in place to promote early deceased donor transplantation in children. Results Preferred allocation in children has been approached in a variety of ways and with varying degrees of commitment in different solid organ transplant disciplines and national medical systems. Conclusion The success of policies to advantage children has varied significantly by both organ and medical system. Further work is needed to optimize allocation strategies for pediatric candidates.
Introduction Envarsus XR® (LCPT), a once daily dosage formulation of tacrolimus, is an FDA‐approved medication in adult renal transplant recipients (RTRs). There are limited data on its pharmacokinetics (PK) in adolescent RTRs. We report here the PK profile of LCPT in adolescent RTRs. Methods The dose of LCPT was determined using a dose conversion ratio targeting 0.7 relative to the total daily immediate‐release tacrolimus (IR‐Tac) dose. On day 7 after converting to LCPT, patients had an abbreviated PK assessment with sampling at: 0 h (pre‐dose), 8‐, and 12‐h post‐dose. The PK data analysis was performed using Bayesian estimators. Our results were compared to those of published adult PK data for LCPT and pediatric PK data for IR‐Tac and extended release tacrolimus (ER‐Tac) formulation (Advagraf). Results PK data from three adolescent patients on LCPT were evaluated. The mean (±SD) area under the time–concentration curve (AUC) was 240 (±20.22) h*ng/mL. The mean Tmax was 9.01 ± 2.12 h, and the % fluctuation was 77.71 ± 3.96%. The AUC, Tmax, and % fluctuation were similar to reported results in adult patients taking LCPT. The AUC was higher and the Tmax was longer than what has been reported in pediatric patients taking IR‐Tac and ER‐Tac. In addition, the LCPT group showed a lower % fluctuation than patients receiving ER‐Tac. Conclusion The PK evaluation of LCPT in adolescent RTRs showed similar results to adults. Adolescents taking LCPT had a higher AUC, a more attenuated Tmax, and a lower fluctuation than that seen with ER‐Tac in pediatrics.
Alport syndrome is a genetically and phenotypically heterogeneous disorder that can be transmitted in an X-linked, autosomal recessive, or autosomal dominant fashion and can affect glomerular, cochlear, and ocular basement membranes. The disorder results from mutations in the collagen IV genes <i>COL4A5</i> (X chromosome), <i>COL4A3</i>, and <i>COL4A4</i>. Alport patients are at lifetime risk for kidney failure, sensorineural deafness, and ocular abnormalities. Males with Alport syndrome typically present with severe phenotype with progression to end-stage kidney disease and/or sensorineural deafness and eye changes. Females generally having less severe presentation and diagnosis of X-linked Alport syndrome are generally not considered. Here, we report a case of a 3-year-old girl with gross hematuria, proteinuria, and chronic kidney disease who was found to have features of Alport syndrome on kidney biopsy and a sporadic heterozygous pathogenic <i>COL4A5</i> deletion on molecular testing. This case report emphasizes the importance of kidney biopsy and molecular testing in the work up of pediatric patients with hematuria, proteinuria, and/or chronic kidney disease. It is also a poignant illustration that females with heterozygous X-linked <i>COL4A5</i> mutations are often affected patients. It further illustrates the phenomenon of sporadic occurrence of genetic kidney disease in the absence of family history of kidney disease.
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