Chronic allograft nephropathy (CAN) has replaced acute rejection as the major cause of graft loss in renal transplant patients. The potent immunosuppressive regimens that have successfully decreased episodes of acute rejection increase the incidence and severity of viral infections. Multiple lines of evidence identify herpesvirus infections as a potential etiologic factor in the development and progression of CAN. We propose a 2-year prospective study in pediatric and young adult renal transplant recipients to test the following hypotheses; 1) that subclinical herpesvirus infections, in peripheral blood cells and/or renal biopsy tissue, are associated with the development of CAN, 2) that significant immunosuppression, defined by lymphopenia and/or low absolute T helper (CD4+) cell numbers, will correlate with an increased risk of subclinical herpesvirus infections, clinical viral disease, and/or CAN. By prospectively determining the temporal relationships between T-cell immunity, subclinical viral infection, and the development of CAN, these studies may be instrumental in developing preventive and/or treatment measures that can improve graft survival thereby greatly decreasing morbidity and mortality in renal transplant patients. This award will allow the applicant to complete her steady progress towards independence as a clinical researcher. Her completion of a Masters of Public Health in Epidemiology, her participation in numerous epidemiology oriented focus groups, and successful completion of transplantation-related clinical studies as a fellow, have already given her a strong background in clinical research. The expertise of the applicant's mentorship group in the areas of virology, immunology, pathology, and clinical transplant research, as well as the dynamic research environment, core facilities, and atmosphere of collaboration at the University of Washington, will allow the applicant to gain the additional vital skills to achieve her goal of successfully continuing independent clinical research in the field of renal transplantation.
| Smith, Jodi M; Corey, Lawrence; Bittner, Rachel et al. (2010) Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation. J Am Soc Nephrol 21:1579-86 |
| Smith, Jodi M; Corey, Lawrence; Healey, Patrick J et al. (2007) Adolescents are more likely to develop posttransplant lymphoproliferative disorder after primary Epstein-Barr virus infection than younger renal transplant recipients. Transplantation 83:1423-8 |
