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Am J Transplant. 2016 Mar;16(3):921-9. doi: 10.1111/ajt.13649. Epub 2016 Feb 3.

Impact of Everolimus and Low-Dose Cyclosporin on Cytomegalovirus Replication and Disease in Pediatric Renal Transplantation.

Author information

1
Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
2
Hanover Medical School, Hanover, Germany.
3
Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
4
IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
5
Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
6
Department of General Pediatrics, Pediatric Nephrology, University Children's Hospital, Münster, Germany.
7
Olga Children's Hospital, Clinic of Stuttgart, Stuttgart, Germany.
8
Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, UK.
9
Department of Pediatric Nephrology, Adana Teaching and Research Center, Baskent University, Adana, Turkey.
10
Great Ormond Street Hospital, London, UK.
11
Ankara University Faculty of Medicine, Ankara, Turkey.
12
University Children's Hospital, Hamburg, Germany.
13
University Children's Hospital, Tübingen, Germany.
14
University Children's Hospital, Freiburg, Germany.
15
Children's Hospital, Memmingen, Germany.
16
Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.

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.

PMID:
26613840
DOI:
10.1111/ajt.13649
[Indexed for MEDLINE]
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