Study of Subclinical Viral Infection

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.