Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and BK polyomavirus (BKV) are the viruses most often implicated in tissue-invasive disease after solid organ transplantation, yet information about their natural history is incomplete. No carefully designed prospective studies exist to characterize posttransplant infections due to CMV, EBV and BKV. The hypothesis is that CMV, EBV and BKV infections and coinfections, even if asymptomatic, cause posttransplant morbidity. The first specific aim is to perform prospective quantitative virology surveillance of renal and lung transplant patients for up to 5 years.
The second aim has substudies to (a) evaluate oral washes and urine as noninvasive alternatives to blood for monitoring viral infections, (b) examine the effects of prophylactic valganciclovir on all 3 viruses;(c) evaluate weekly viral DMAtesting to uncover short-lived infections that may be clinically important (d) provide urine samples for validation of protein markers that distinguish BKV infection and nephrology. CMB, EBV, and BKV DNA will be quantitated by real-time PCR in oral, urine and blood samples at frequent intervals and antibodies to CMV and EBV will be measured. Viral CAN will be quantitated in bronchoalveolar lavage (BAL) samples from lung transplant patients. Donors will be tested at transplant. Quantitative virologic data will be correlated with clinical data from the Research Database of the Kidney and Pancreas Organ Transplant Tracking System, the lung transplant program's O'Brien Biobank and Database, and information from a questionnaire about intercurrent infections. National history characteristics to be examined as predictors, risk factors, and comorbidities include: (1) Baseline CMV and EBV antibody status of donor and recipient. (2) Response to transplant valganciclovir prophylaxis: viral load pre- and post-prophylaxis in oral washes, blood, BAL (lung transplant recipients only) and urine. (3) Serial measurements of CMV, EBV, and BKV viral loads, which will be treated as continuous as well as categorical variables in an analysis of the threshold for developing tissue-invasive disease. Relations of these continuous and categorical natural history characteristics with clinical endpoints will be examined by exploratory graphical methods, cross-classified tables of counts, and comparisons between and within subgroups, and modeled using linear and categorical mixed-effects models for longitudinal measurements. This research will fill a critical gap by identifying risk factors for morbidity due CMV, EBV, and BKV infections that will guide evidence-based strategies for managing these infections.

Public Health Relevance

(Seeinstructions): Relevance to public health: Viral infections are a major complication for the -29,000 patients who receive a solid organ transplant annually in the U.S.
This research aims to define risk factors for posttransplant morbidity due to Cytomegalovirus, Epstein-Barr virus, and BK polyomavirus, which would form the basis for designing scientifically sound management strategies.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-R)
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University of Minnesota Twin Cities
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