title: Impact of Everolimus and Low-Dose Cyclosporin on Cytomegalovirus Replication and Disease in Pediatric Renal Transplantation.
abstract: In order to investigate the hypothesis that the mammalian target of rapamycin inhibitor everolimus (EVR) shows anticytomegalovirus (CMV) activity in pediatric patients, we analyzed the impact of EVR-based immunosuppressive therapy on CMV replication and disease in a large cohort (n = 301) of pediatric kidney allograft recipients. The EVR cohort (n = 59), who also received low-dose cyclosporin, was compared with a control cohort (n = 242), who was administered standard-dose cyclosporin or tacrolimus and an antimetabolite, mostly mycophenolate mofetil (91.7%). Multivariate analysis revealed an 83% lower risk of CMV replication in the EVR cohort than in the control cohort (p = 0.005). In CMV high-risk (donor+/recipient-) patients (n = 88), the EVR-based regimen was associated with a significantly lower rate of CMV disease (0% vs. 14.3%, p = 0.046) than the standard regimen. In patients who had received chemoprophylaxis with (val-)ganciclovir (n = 63), the CMV-free survival rates at 1 year and 3 years posttransplant (100%) were significantly (p = 0.015) higher in the EVR cohort (n = 15) than in the control cohort (n = 48; 1 year, 75.0%; 3 years, 63.3%). Our data suggest that in pediatric patients at high risk of CMV, an EVR-based immunosuppressive regimen is associated with a lower risk of CMV disease than a standard-dose calcineurin inhibitor-based regimen.
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Höcker
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zencke
authors.affiliation: Hanover Medical School, Hanover, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Pape
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Krupka
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.|Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Köster
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fichtner
authors.affiliation: IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Dello Strologo
authors.affiliation: IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Guzzo
authors.affiliation: Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: R
authors.initials: R
authors.lastname: Topaloglu
authors.affiliation: Department of General Pediatrics, Pediatric Nephrology, University Children's Hospital, Münster, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kranz
authors.affiliation: Department of General Pediatrics, Pediatric Nephrology, University Children's Hospital, Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: König
authors.affiliation: Olga Children's Hospital, Clinic of Stuttgart, Stuttgart, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bald
authors.affiliation: Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, UK.
authors.forename: N J A
authors.initials: NJ
authors.lastname: Webb
authors.affiliation: Department of Pediatric Nephrology, Adana Teaching and Research Center, Baskent University, Adana, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Noyan
authors.affiliation: Department of Pediatric Nephrology, Adana Teaching and Research Center, Baskent University, Adana, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Dursun
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Marks
authors.affiliation: Ankara University Faculty of Medicine, Ankara, Turkey.
authors.forename: Z B
authors.initials: ZB
authors.lastname: Ozcakar
authors.affiliation: University Children's Hospital, Hamburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Thiel
authors.affiliation: University Children's Hospital, Tübingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Billing
authors.affiliation: University Children's Hospital, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pohl
authors.affiliation: Children's Hospital, Memmingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Fehrenbach
authors.affiliation: Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schnitzler
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Hanover Medical School, Hanover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ahlenstiel-Grunow
authors.affiliation: Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Tönshoff
mesh_terms: D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage*; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000517:prevention & control* / Q000821:virology; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control* / Q000821:virology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus