Abstract

Abstract Background and Aims Non-invasive monitoring strategies are insufficient to detect patients at risk for subclinical graft rejection after kidney transplantation. The highly prevalent and non-pathogenic Torque Teno virus (TTV) reflects the immunocompetence of its host: high level viraemia indicates strong and low level viraemia weak immunosuppression, respectively. Thus TTV replication might serve as a candidate for immunologic monitoring. Method To analyze the association between TTV and subclinical kidney graft rejection, an interim analysis of the prospective “TTV POET” cohort study (DRKS00012335) was performed including data available until 31/01/2019. All consecutive kidney graft recipients transplanted at the Medical University Vienna since 01/12/2016 (n=308) with a protocol biopsy 12 months after transplantation (n=47; median 12.4 months) and stable graft function were included. Biopsy results according to current BANFF classification were analyzed in the context of peripheral blood TTV levels quantified by PCR. Results Graft function was excellent (median eGFR MDRD: 57 ml/min/1.73m2, urinary PKR: 92 mg/g). Twenty recipients (43%) had subclinical rejection (borderline TCMR, n=16; ABMR, n=3; TCMR type I, n=1). TTV level quantified at the date of biopsy was lower in recipients with rejection compared to recipients without rejection. The risk for rejection increased by 11% with each log level decrease in TTV copies/ml (RR 0.89, 95% CI 0.85-0.93; p<0.001). Differences in TTV levels were evident not only at the date of biopsy, but already 6 weeks earlier. Patients with biopsies showing chronic leasons, suggesting ongoing allo-reactivity, had a longer period of time with TTV levels <1x106 copies/ml. Conclusion Our data suggests an association between TTV level and subclinical graft rejection at 12 months after kidney transplantation. Future clinical trials are necessary to test the potential of TTV guided immunosuppression to reduce subclinical rejection.

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