title: Increased osteoprotegerin predicts poor virological outcome during anticytomegalovirus therapy in solid organ transplant recipients.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection involves interaction between endothelial cells and leukocyte subsets that may promote vascular inflammation and lead to treatment failure in infected individuals. Osteoprotegerin is a marker of vascular and systemic inflammation but has not been investigated in relation to treatment outcome during CMV infection.
  
  
  METHODS
  We investigated whether circulating levels of osteoprotegerin are related to features of CMV disease and treatment outcomes during CMV infection in 291 solid organ transplant recipients receiving valganciclovir or ganciclovir in an international multicenter trial of CMV disease treatment (the VICTOR study).
  
  
  RESULTS
  Elevated plasma osteoprotegerin was associated with (i) certain disease characteristics including presence of tissue invasive disease (P<0.05) and increased viral load at baseline (P<0.05), (ii) poor virological outcome at day 49 after anti-CMV therapy, (iii) increased plasma levels of markers of inflammation (pentraxin 3 and C-reactive protein) and endothelial cell activation (von Willebrand factor) both at baseline and during follow-up.
  
  
  CONCLUSIONS
  Our finding indicates that elevated osteoprotegerin levels in solid organ transplant recipients with CMV infection may reflect vascular inflammation and is associated with late virological outcome in these patients.
authors.affiliation: 1 Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 2 Department of Microbiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 3 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway. 4 Department of Organ Transplantation, Gastroenterology and Nephrology, Section for Nephrology, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway. 5 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. 6 Faculty of Medicine, University of Oslo, Oslo, Norway. 7 K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway. 8 Institute of Cardiovascular and Medical Sciences University of Glasgow, Glasgow, United Kingdom. 9 Department of Medicine, University of Alberta, Edmonton, Canada. 10 School of Specialization in Hospital Pharmacy, University of Milan, Milan, Italy.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Halvor
authors.initials: H
authors.lastname: Rollag
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.forename: Alan
authors.initials: A
authors.lastname: Jardine
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Bignamini
authors.forename: Anders
authors.initials: A
authors.lastname: Åsberg
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D053244:Osteoprotegerin / Q000097:blood*; D000683:Serum Amyloid P-Component / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D000077562:Valganciclovir; D019562:Viral Load; D014841:von Willebrand Factor / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D015774:Ganciclovir; D018836:Inflammation Mediators; D053244:Osteoprotegerin; D000683:Serum Amyloid P-Component; D000077562:Valganciclovir; D014841:von Willebrand Factor; D000099153:Pentraxins; C506030:TNFRSF11B protein, human