title: Primary Cytomegalovirus Infection in Seronegative Kidney Transplant Patients Is Associated with Protracted Cold Ischemic Time of Seropositive Donor Organs.
abstract: Human Cytomegalovirus (CMV) can lead to primary infection or reactivation in CMV-seronegative or -seropositive kidney transplant recipients, respectively. Complications comprise severe end-organ diseases and acute or chronic transplant rejection. Risk for CMV manifestation is stratified according to the CMV-IgG-serostatus, with donor+/recipient- (D+/R-) patients carrying the highest risk for CMV-replication. However, risk factors predisposing for primary infection in CMV-seronegative recipients are still not fully elucidated. Therefore, we monitored D+/R- high-risk patients undergoing kidney transplantation in combination with antiviral prophylaxis for the incidence of CMV-viremia for a median follow-up time of 784 days (156-1155 days). In this period, we analyzed the functional CMV-specific T cell response by intracellular cytokine staining and CMV-serology by ELISA. Only four of eight D+/R- patients developed clinically relevant CMV-viremia followed by seroconversion. Viremia triggered expansion of functional CMV-specific T cells correlating with protection against secondary CMV-reactivations. In contrast, all other patients remained permanently aviremic and showed no immunological correlate of infection after discontinuation of antiviral prophylaxis for up to three years. Comparing cold ischemic times (CIT) of viremic (median = 1020 min; 720-1080 min) and aviremic patients (median = 335 min; 120-660 min) revealed significantly (p = 0.0286) protracted CIT in patients with primary CMV-infection. Taken together, primary CMV-infection affects only a subgroup of D+/R- patients correlating with length of CIT. Therefore, patients with extended CIT should be thoroughly monitored for CMV-replication well beyond discontinuation of antiviral prophylaxis. In contrast, patients with short CIT remained permanently uninfected and might benefit from shorter prophylactic treatment.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schlott
authors.affiliation: Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Steubl
authors.affiliation: Institute of Virology, Technische Universität München/ Helmholtz Zentrum München, Munich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoffmann
authors.affiliation: German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.|Department of Surgery, Transplantationszentrum München Klinikum Rechts der Isar, Technical University München, Munich, Germany.
authors.forename: Edouard
authors.initials: E
authors.lastname: Matevossian
authors.affiliation: Section of Nephrology, I. Department of Medicine, Johannes-Gutenberg University Mainz, Mainz, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Lutz
authors.affiliation: German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.|Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.affiliation: Technical University Munich, Chair of Biomathematics, Garching, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Hösel
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.|Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Renders
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Neuenhahn
mesh_terms: D050377:Cold Ischemia; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D065288:Serogroup; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014019:Tissue Donors; D014766:Viremia / Q000276:immunology / Q000473:pathology / Q000821:virology