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.
(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.
|Vezina, Heather E; Brundage, Richard C; Balfour Jr, Henry H (2014) Population pharmacokinetics of valganciclovir prophylaxis in paediatric and adult solid organ transplant recipients. Br J Clin Pharmacol 78:343-52|
|Balfour Jr, Henry H (2014) Editorial commentary: Genetics and infectious mononucleosis. Clin Infect Dis 58:1690-1|
|Nevins, Thomas E; Robiner, William N; Thomas, William (2014) Predictive patterns of early medication adherence in renal transplantation. Transplantation 98:878-84|
|Balfour Jr, Henry H (2014) Progress, prospects, and problems in Epstein-Barr virus vaccine development. Curr Opin Virol 6:1-5|
|Verghese, Priya S; Dunn, Ty B; Chinnakotla, Srinath et al. (2014) Calcineurin inhibitors in HLA-identical living related donor kidney transplantation. Nephrol Dial Transplant 29:209-18|
|Suszynski, Thomas M; Rizzari, Michael D; Gillingham, Kristen J et al. (2013) Antihypertensive pharmacotherapy and long-term outcomes in pediatric kidney transplantation. Clin Transplant 27:472-80|
|Najafian, Behzad; Mauer, Michael (2013) Predilection of segmental glomerulosclerosis lesions for the glomerulotubular junction area in type 1 diabetic patients: a novel mapping method. PLoS One 8:e69253|
|Mauer, Michael; Fioretto, Paola (2013) Pancreas transplantation and reversal of diabetic nephropathy lesions. Med Clin North Am 97:109-14|
|Ponchiardi, Cecilia; Mauer, Michael; Najafian, Behzad (2013) Temporal profile of diabetic nephropathy pathologic changes. Curr Diab Rep 13:592-9|
|Suszynski, T M; Gillingham, K J; Rizzari, M D et al. (2013) Prospective randomized trial of maintenance immunosuppression with rapid discontinuation of prednisone in adult kidney transplantation. Am J Transplant 13:961-70|
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