P1624TORQUE TENO VIRUS FOR RISK STRATIFICATION OF GRAFT REJECTION AND INFECTION IN KIDNEY TRANSPLANT RECIPIENTS - A PROSPECTIVE OBSERVATIONAL TRIAL

Abstract

Abstract Background and Aims The non-pathogenic and ubiquitous Torque Teno virus (TTV) is associated with immunosuppression in solid organ transplant recipients. Studies in kidney transplant patients proposed TTV quantification for risk stratification of graft rejection and infection. This prospective observational trial was designed to assess the potential of TTV load for risk prediction of both, infection and rejection in the first year after transplantation. The objective of this trial was to provide TTV cut-off level to define an optimal TTV range as a basis for a randomised controlled interventional trial to test the efficacy of TTV-guided immunosuppression. Method Within this trial (DRKS00012335) all 386 adult (≥18 years of age) consecutive kidney graft recipients transplanted at the Medical University Vienna, Austria, between January 1st 2016 and June 31st 2018. were subjected to longitudinal per protocol TTV monitoring. In total 3265 TTV measurements were taken and 71 biopsy proven graft rejections (defined by BANFF classification) and 472 clinically relevant infections were documented in the first year post-transplant. After reaching steady state at the end of post-transplant month 3, peripheral TTV plasma load was analyzed in the context of subsequent rejection and infection by rt-PCR. Results Patients with allograft rejection had lower levels of TTV compared to patients without rejection (median 3.5x106 c/mL, IQR 1.7x105-1.3x108 c/ml vs. median 2.5x108 c/mL, IQR 5.8x106-9.3x108 c/mL; P = .028) in subsequent biopsies. TTV load in individuals experiencing an infectious event in the subsequent observation period was higher compared to patients without infection (median 3.9x108 c/mL, IQR 7.9x106-3.3x109 c/mL vs. median 2.6x107 c/mL, IQR 1.3x106-9.2x108 c/mL; P < .001). Of note, TTV was quantified several weeks before rejection diagnosis and infection onset. Each log increase in TTV load decreased the odds for rejection by 22% (OR 0.78, 95% CI 0.62-0.97; P = .027) and increased the odds for infection by 11% (OR 1.11, 95% CI 1.06-1.15; P < .001). The association of TTV and infection and rejection, respectively was not altered by confounding or effect modification. A TTV load between 106 and 108 copies/mL was defined as optimal range to minimize the risk for rejection and infection. Conclusion These data support the initiation of an interventional trial assessing the efficacy of TTV-guided immunosuppression to reduce infection and graft rejection in kidney transplant recipients.