Subclinical Viral Infection and Renal Allograft Injury

Chronic allograft injury is the leading cause of graft loss in renal transplantation. The shortage of available kidneys for transplantation has reached crisis levels with increasing numbers of waiting list mortalities. Strategies to prolong graft survival are urgently needed. The pediatric and young adult transplant population is one in which repeat transplantation is inevitable and therefore, this group is one who will especially benefit from intervention to prolong graft survival. The hypothesis of this proposal is that subclinical viral infection is a modifiable risk factor in the pathogenesis of chronic allograft injury. The young age of the proposed study population is an ideal one to evaluate this objective due to the high prevalence of seronegative recipients. The studies outlined will determine the temporal relationship betWeween subclinical viremia, renal allograft infection and allograft injury. This will be the first prospective study in renal transplant recipients to systematically monitor subclinical viral infection both in peripheral blood and in the renal allograft with concurrent quantitative measures of renal function, allograft fibrosis, and innate immune activation. The investigators have chosen these 3 outcomes because they evaluate a spectrum of renal allograft injury and represent different stages - from early to late - in the pathophysiology that leads to renal allograft dysfunction. In addition, the role of virus specific T cell immune responses in the control of subclinical viral infection and associated allograft injury will be determined. These data are critical as they will provide insights into the pathogenesis of injury and will guide development of interventions strategies. Importantly, the current treatment strategies for viral disease do not prevent subclinical viral infection. Thus, the results of this study may identify that prevention, prophylaxis and/or treatment of subclinical viral replication as a long term strategy to prevent chronic allograft injury and prolong graft survival.