Our studies based on Thymoglobulin, cyclosporine, azathioprine and prednisone resulted in a 1-year rejection rate of 4% and 3-year graft survival of 95%. Use of tacrolimus, compared to cyclosporine, has been associated with lower rejection rates and better graft survival. The incidence of polyoma virus infection may increase with tacrolimus. Polyoma virus has a 60-80% seroprevalence in the general population and reactivation after transplant is common. It is an important cause of graft dysfunction with graft loss in 50% of cases. The incidence, natural history, the role of tacrolimus or cyclosporine on the incidence of reactivation; the relationship of viruruia, viremia, invasive disease and renal dysfunction; and whether other viruses are co-factors for polyoma infection are unknown. Thus, this study has 3 Specific Aims.
Aim 1 : To determine the incidence, natural history and associated factors of polyoma infection from the time of transplant and over 1-year in a large cohort (n=250) of new renal transplant recipients monitored with PCR of urine, plasma, and whole blood weekly for 16 weeks and at months 4, 5, 6, 9 and 12, in patients treated with tacrolimus or cyclosporine.
Aim 2 : To determine the relationship among tissue, blood and urine polyoma-PCR and renal allograft pathology, by analyzing conventional histopathology, immunohistochemistry, in situ hybridization, and tissue, blood and urine-PCR for polyoma in renal transplant recipients with graft dysfunction.
Aim 3 : To determine whether active polyoma virus infection is a co-factor in the 10-20% of patients who develop active CMV, HHV-6, or HHV-7 after discontinuation of oral ganciclovir prophylaxis compared to the 80-90% of patients at risk who do not develop CMV disease.The candidate is a patient-oriented researcher and an Established Investigator for the American Heart Association and a Young Investigator for the American Society of Transplantation. He has or currently mentored 13 patient-oriented researchers. This award and project will allow him to improve his own patient-oriented research and mentoring capabilities. It will allow him to increase the number and more formally mentor the patient-oriented training of fellows and junior faculty.
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|Anwar, Siddiq; Larson, Derek S; Naimi, Nima et al. (2015) A case report of adrenocorticotropic hormone to treat recurrent focal segmental glomerular sclerosis post-transplantation and biomarker monitoring. Front Med (Lausanne) 2:13|
|Lim, Efrem S; Reyes, Alejandro; Antonio, Martin et al. (2013) Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing. Virology 436:295-303|
|Pastrana, Diana V; Brennan, Daniel C; Cuburu, Nicolas et al. (2012) Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients. PLoS Pathog 8:e1002650|
|Java, Anuja; Gaut, Joseph P; Brennan, Daniel C (2012) De novo membranoproliferative glomerulonephritis III in a renal transplant patient: case report and review of the literature. Transpl Int 25:e58-61|
|Machnicki, Gerardo; Lentine, Krista L; Salvalaggio, Paolo R et al. (2011) Three-year post-transplant Medicare payments in kidney transplant recipients: associations with pre-transplant comorbidities. Saudi J Kidney Dis Transpl 22:24-39|
|Lentine, Krista L; Schnitzler, Mark A; Xiao, Huiling et al. (2010) Racial variation in medical outcomes among living kidney donors. N Engl J Med 363:724-32|
|Spinner, Michael L; Saab, Georges; Casabar, Ed et al. (2010) Impact of prophylactic versus preemptive valganciclovir on long-term renal allograft outcomes. Transplantation 90:412-8|
|Boothpur, Raghavender; Brennan, Daniel C (2010) Human polyoma viruses and disease with emphasis on clinical BK and JC. J Clin Virol 47:306-12|
|Hardinger, Karen L; Rasu, Rafia S; Skelton, Rebecca et al. (2010) Thymoglobulin induction dosing strategies in a low-risk kidney transplant population: three or four days? J Transplant 2010:957549|
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