Torquetenovirus viremia for early prediction of graft rejection after kidney transplantation
Introduction
Long-term graft function and survival after kidney transplantation relies on suitable immunosuppressive treatment to provide an optimal balance between rejection and infection risks. BK virus (BKV)-associated nephropathy (BKVAN) and graft rejection are major causes of graft dysfunction and loss in kidney transplant recipients (KTR).1 The disruption of the balance between BKV replication and host immune control is a key element of viral pathogenesis.2 Torquetenovirus (TTV) is a small, non-enveloped, single-stranded DNA virus of the Anelloviridae family which has not been linked to any specific human illness but represents a major component of the human virome.3 Indeed, immunocompetent hosts display low-level viremia while TTV loads are substantially higher in immunocompromised patients.4 In lung and heart transplant recipients, high TTV loads correlate with high doses of immunosuppressive drugs and are associated with microbial infection occurrence,5, 6 while low levels of TTV viremia are observed in patients with graft rejection episodes.3 These data suggest that TTV viremia may be linked to BKV replication and/or graft rejection in KTR. In this work, we investigated long-term TTV load kinetics at transplantation and over 24 months in a well-characterized KTR cohort. We analyzed TTV loads according to patient characteristics, immunosuppressive drugs, BKV replication status and rejection episodes, in order to determine if TTV viremia may adequately reflect the degree of immunosuppression and represent a useful predictor of BKV replication and/or graft rejection.
Section snippets
Patients
Sixty-six adult patients who underwent kidney transplantation between July 2012 and July 2014 in Strasbourg University Hospitals were enrolled in this study. The present study was based on a prospective longitudinal study on anti-BKV neutralizing antibodies (Clinical Trials.gov identifier: NCT02826811). The design of the study has earlier been reported in detail.7 Briefly, all patients who displayed BKV replication in urine in the first two years post-transplantation (n = 50) were included.
TTV load kinetics
Patient characteristics are presented in Table 1. Positive TTV viremia was detected in 86% of KTR on the day of transplantation (D0) with a mean load of 3.06 log10 copies/mL, and in 96% of patients during follow-up. Only TTV-positive patients were subsequently considered for the analysis of TTV loads (n = 63). TTV kinetics showed an increasing phase up until M (month) 3 (M1 mean TTV load: 4.35 log10 copies/mL, M3 mean TTV load: 6.79 log10 copies/mL) with a 98% probability for TTV viremia to
Discussion
In this long-term longitudinal study on KTR, for the first time, we (i) describe a relationship between TTV and BKV viremia and (ii) determine cutoff values of TTV viremia allowing to identify, as early as in the first month after transplantation, the patients who are at high risk of graft rejection.
Longitudinal TTV load dynamics in KTR are characterized by a first increasing phase from baseline to M3, and a decreasing phase from M3 to M24. Some shorter-term studies in KTR have been published
Acknowledgments
The TTV R-GENE® kits used in this study were kindly provided by Philippe Bourgeois and Carole Janis, bioMérieux, Marcy l'Etoile, France.
Declarations of interest
None
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