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Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept
Authors:Nathalie Chavarot  Gillian Divard  Anne Scemla  Lucile Amrouche  Olivier Aubert  Marianne Leruez-Ville  Marc O Timsit  Claire Tinel  Julien Zuber  Christophe Legendre  Dany Anglicheau  Rebecca Sberro-Soussan
Institution:1. Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;2. INSERM, Paris Translational Research Centre for Organ Transplantation, Paris, France;3. Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France

Université de Paris, Paris, France;4. Département of Virology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;5. Université de Paris, Paris, France

Department of Urology, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;6. Necker-Enfants Malades Institute, French National Institute of Health and Medical Research U1151, Paris, France

Abstract:Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age IQR] 59.2 years 45.4–68.5]) were converted to belatacept (median of 11.5 months 2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls 2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients 60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 80%]) and life-threatening diseases (4/40 10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.
Keywords:clinical research/practice  complication: infectious  immunosuppressant – fusion proteins and monoclonal antibodies  immunosuppression/immune modulation  immunosuppressive regimens – rescue  infection and infectious agents – viral: Cytomegalovirus (CMV)  infectious disease  kidney transplantation/nephrology
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