Drug level variability in children after renal transplant and transition of care

Columbia University Health Sciences, New York NY

Investigators

Abstract

DESCRIPTION (provided by applicant): The transition of pediatric recipients of solid-organ transplants to adult-oriented services has been demonstrated to be associated with worse allograft outcomes following the transition of care. This proposed project will advance scientific knowledge to test specific metrics to predict risk of allograft rejection. Previous studies have aimed to predict the association between non-adherence and allograft loss. The literature on transition of care lacks information about how the variability of immunosuppressive drug trough patterns of pediatric transplant recipients affects donor specific anti-HLA antibody status and their risk of allograft rejection. We propose a retrospective study using a cohort of pediatric renal transplant recipients from Children's Hospital of Philadelphia from January 1999 to December 2010, and the subset that transferred their care to adult-oriented service. The study design will enable the applicant to achieve the following Specific Aims: 1a) To assess whether variability in immunosuppressive drug trough levels as measured by percent coefficient of variation (CV%) of tacrolimus (TAC) or sirolimus (SRL) is associated with development of de novo DSA in pediatric transplant recipients~ 1b) To assess whether de novo DSA is associated with increased risk for allograft rejection~ 2) To assess the association of CV% of TAC or SRL in pediatric renal transplant recipients with changes in estimated glomerular filtration rate (eGFR) in two-year follow-up post-transplant~ 3a) To assess change in CV% of tacrolimus (TAC) or sirolimus (SRL) in pediatric renal transplant recipients one year prior to and 18 months following transition of care to adult providers~ and 3b) To assess whether CV% of TAC or SRL in pediatric transplant recipients following transition is associated with increased incidence of allograft rejection. The result of this study could help clinicians to identify vulnerable pediatic renal allograft recipients who would benefit from increased surveillance or lead to the development of improved health care systems to improve patient and allograft outcomes. The proposed research project will be in the context of the applicant completing requirements for a Masters of Science in Clinical Epidemiology degree. The degree program will encompass intensive instruction on the fundamentals of epidemiology, biostatistics, study design, data management, and analytic methods~ this coursework will enhance and guide the research process of the applicant. The program will also involve multi- faceted career development with complementary mentors with expertise in epidemiology research, health services research, clinical transplantation and nephrology. The longer-term objectives of the applicant for this grant are to collect and analyze the data, prepare manuscripts for publication, apply the results to the design of future prospective studies, and use the results as a foundation for a future K-award application.