BKV, CMV, and EBV Interactions and their Effect on Graft Function One Year Post-Renal Transplantation: Results from a Large Multi-Centre StudyResearch in context
Arturo Blazquez-Navarro,
Chantip Dang-Heine,
Nicole Wittenbrink,
Chris Bauer,
Kerstin Wolk,
Robert Sabat,
Timm H. Westhoff,
Birgit Sawitzki,
Petra Reinke,
Oliver Thomusch,
Christian Hugo,
Michal Or-Guil,
Nina Babel
Affiliations
Arturo Blazquez-Navarro
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Philippstr. 13, 10115 Berlin, Germany
Chantip Dang-Heine
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Nicole Wittenbrink
Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Philippstr. 13, 10115 Berlin, Germany
Chris Bauer
MicroDiscovery GmbH, Marienburger Str. 1, 10405 Berlin, Germany
Kerstin Wolk
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Psoriasis Research and Treatment Center, Institute of Medical Immunology, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
Robert Sabat
Psoriasis Research and Treatment Center, Institute of Medical Immunology, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Interdisciplinary Group of Molecular Immunopathology, Institute of Medical Immunology, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Timm H. Westhoff
Medical Department 1, Universitätsklinikum der Ruhr-Universität Bochum, Ruhr-Universität Bochum, Hölkeskampring 40, 44625 Herne, Germany
Birgit Sawitzki
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Molecular Immune Modulation, Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Petra Reinke
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin Center for Advanced Therapies (BeCAT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Oliver Thomusch
Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany
Christian Hugo
Universitätsklinikum Carl Gustav Carus, Medizinische Klinik III - Bereich Nephrologie, Fetscherstraße 74, 01307 Dresden, Germany
Michal Or-Guil
Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Philippstr. 13, 10115 Berlin, Germany; Correspondence to: Michal Or-Guil, Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Philippstr. 13, 10115 Berlin, Germany
Nina Babel
Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Medical Department 1, Universitätsklinikum der Ruhr-Universität Bochum, Ruhr-Universität Bochum, Hölkeskampring 40, 44625 Herne, Germany; Correpondence to: Nina Babel, Medical Department 1, Universitätsklinikum der Ruhr-Universität Bochum, Ruhr-Universität Bochum, Hölkeskampring 40, 44625 Herne, Germany
Background: BK virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations are common after kidney transplantation and associated with increased morbidity and mortality. Although CMV might be a risk factor for BKV and EBV, the effects of combined reactivations remain unknown. The purpose of this study is to ascertain the interaction and effects on graft function of these reactivations. Methods: 3715 serum samples from 540 kidney transplant recipients were analysed for viral load by qPCR. Measurements were performed throughout eight visits during the first post-transplantation year. Clinical characteristics, including graft function (GFR), were collected in parallel. Findings: BKV had the highest prevalence and viral loads. BKV or CMV viral loads over 10,000 copies·mL−1 led to significant GFR impairment. 57 patients had BKV-CMV combined reactivation, both reactivations were significantly associated (p = 0.005). Combined reactivation was associated with a significant GFR reduction one year post-transplantation of 11.7 mL·min−1·1.73 m−2 (p = 0.02) at relatively low thresholds (BKV > 1000 and CMV > 4000 copies·mL−1). For EBV, a significant association was found with CMV reactivation (p = 0.02), but no GFR reduction was found. Long cold ischaemia times were a further risk factor for high CMV load. Interpretation: BKV-CMV combined reactivation has a deep impact on renal function one year post-transplantation and therefore most likely on long-term allograft function, even at low viral loads. Frequent viral monitoring and subsequent interventions for low BKV and/or CMV viraemia levels and/or long cold ischaemia time are recommended. Fund: Investigator Initiated Trial; financial support by German Federal Ministry of Education and Research (BMBF). Keywords: BK virus, Cytomegalovirus, Epstein-Barr virus, Kidney transplantation, Graft function, Combined reactivation