Increased osteoprotegerin predicts poor virological outcome during anticytomegalovirus therapy in solid organ transplant recipients.

Abstract

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. 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). 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. 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.