Renal function in the long term after pediatric liver transplantation: is there a need for protocol kidney biopsies?
ABSTRACT With improving survival rates following solid organ transplantation, assessment of its success has broadened with a focus on long-term outcomes, including nongraft-related medical outcomes and family and patient perceptions of quality of life. Posttransplant renal dysfunction contributes to long-term morbidity and mortality following pediatric liver transplantation. In this review, we provide an overview of our understanding and approach to managing posttransplant renal dysfunction and highlight the existing gaps in knowledge in this area.
The literature regarding renal dysfunction following liver transplant primarily focuses on the experience in the adult population. Studies on children are limited by small numbers and varying definitions of outcomes. Thus, lessons in the current literature must be closely examined before they can be extrapolated and applied to children.
The current literature validates that posttransplant renal dysfunction is a frequent and important outcome for adults and children. Although the characteristics of children at high risk are less clear, calcineurin inhibitor minimization is considered a viable strategy for preserving renal function. The risk-benefit ratio of kidney biopsy in children and the possibility of renal preservation via immunosuppression withdrawal are intriguing concepts that remain to be defined.
SourceAvailable from: Martin Jankofsky[Show abstract] [Hide abstract]
ABSTRACT: During the last 5 decades, liver transplantation has witnessed rapid development in terms of both technical and pharmacologic advances. Since their discovery, calcineurin inhibitors (CNIs) have remained the standard of care for immunosuppression therapy in liver transplantation, improving both patient and graft survival. However, adverse events, particularly posttransplant nephrotoxicity, associated with long-term CNI use have necessitated the development of alternate treatment approaches. These include combination therapy with a CNI and the inosine monophosphate dehydrogenase inhibitor mycophenolic acid and use of mammalian target of rapamycin (mTOR) inhibitors. Everolimus, a 40-O-(2-hydroxyethyl) derivative of mTOR inhibitor sirolimus, has a distinct pharmacokinetic profile. Several studies have assessed the role of everolimus in liver transplant recipients in combination with CNI reduction or as a CNI withdrawal strategy. The efficacy of everolimus-based immunosuppressive therapy has been demonstrated in both de novo and maintenance liver transplant recipients. A pivotal study in 719 de novo liver transplant recipients formed the basis of the recent approval of everolimus in combination with steroids and reduced-dose tacrolimus in liver transplantation. In this study, everolimus introduced at 30 days posttransplantation in combination with reduced-dose tacrolimus (exposure reduced by 39%) showed comparable efficacy (composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, or death) and achieved superior renal function as early as month 1 and maintained it over 2 years versus standard exposure tacrolimus. This review provides an overview of the efficacy and safety of everolimus-based regimens in liver transplantation in the de novo and maintenance settings, as well as in special populations such as patients with hepatocellular carcinoma recurrence, hepatitis C virus-positive patients, and pediatric transplant recipients. We also provide an overview of ongoing studies and discuss potential expansion of the role for everolimus in these settings.Clinical and Experimental Gastroenterology 01/2014; 7:329-43. DOI:10.2147/CEG.S41780
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ABSTRACT: Background: Vascularized composite allotransplantation (VCA) has experienced a growing acceptance, which has led to a debate centered on extending the indications of the procedure to include pediatric patients. The aim of this article was to discuss such indications based on the evidence in pediatric solid organ transplantation, reconstructive surgery in children, and VCA in adult patients. Methods: Papers published on the outcomes of pediatric solid organ transplantation, growth after replantation of extremities, vascularized autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial fractures, and outcomes after repair of peripheral nerves in children were reviewed. Results: Although the outcomes of solid organ transplantation in children have improved, the transplanted organs continue to have a limited lifespan. Long-term immunosuppressive therapy exposes the patients to an increased lifetime risk of infections, diabetes, hypertension, dyslipidemia, cardiovascular disease, and malignancy. Growth impairment and learning disabilities are other relevant drawbacks, which affect the pediatric recipients. Nonadherence to medication is a common cause of graft dysfunction and loss among the adolescent transplant recipients. Rejection episodes, hospitalizations, and medication adverse effects contribute negatively to the quality of life of the patients. Although normal growth after limb transplantation could be expected, pediatric facial transplant recipients may present with arrest of growth of transplanted midfacial skeleton. Conclusions: Considering the non-life-threatening nature of the conditions that lead to eligibility for VCA, it is suggested that it is premature to extend the indications of VCA to include pediatric patients under the currently available immunosuppressive protocols.Annals of Plastic Surgery 07/2014; 73(4). DOI:10.1097/SAP.0000000000000300 · 1.46 Impact Factor