Cytomegalovirus Serology and Replication Remain Associated With Solid Organ Graft Rejection and Graft Loss in the Era of Prophylactic Treatment

Abstract

Cytomegalovirus replication and donor or recipient seroconstellation remains associated with graft rejection and graft loss in the era of prophylactic CMV treatment.

Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses

“…Universal prophylaxis and preemptive therapy have been used to manage CMV infection, but both are associated with disadvantages (1,2,4). Universal prophylaxis is not fully effective, its duration, 3-6 months, varies according to the perceived risk, is associated with bone marrow adverse events possibly leading to drug dose discontinuation (5,6), and is associated with significant incidence of late CMV infection and drug resistance (2,(7)(8)(9). Pre-emptive therapy does not prevent viral replication, an event that has been associated with inferior transplant outcomes, and requires intensive logistical coordination (2,4,(10)(11)(12).…”

The Cell Biology of Cytomegalovirus: Implications for Transplantation

“…CMV has multiple additional survival strategies that target hosts' adaptive and innate immune functions, that diminish mobilization of phagocytes and antigen presentation, and that produce homologs of host cytokine and chemokine receptors (1-7); however, the mechanisms linking CMV infection with diminished graft function are incompletely understood (8). CMV infections of grafts cause what have been termed "direct effects" in the allograft, including inflammation, vasculopathy and fibrosis with resultant chronic allograft dysfunction (9)(10)(11)(12). "Indirect effects," or systemic effects beyond those attributable to direct viral injury, are mediated by upregulation of specific T and B cell alloimmune responses by innate immune mechanisms (inflammatory mediators, mobilization of antigenpresenting cells with improved antigen presentation, diminished regulatory responses) or by stimulation of alloimmunity by cross-reactive viral antigens with resultant graft injury.…”

Infection in Renal Transplant Recipients

“…[44][45][46] These later infections are differentiated from those occurring shortly after suspension of prophylaxis by their later acquisition, worse allograft function, higher mortality, and absence of association with CMV donor-positive, recipient-negative (D+/R-) serostatus. 47,48 Although the association between CMV and rejection and allograft damage has been recognized for years, the exact mechanism is not known. 1,40 The most common direct effects are asymptomatic viremia; CMV syndrome, which can include fever, malaise, and cytopenias (usually leukopenia and/or thrombocytopenia); and gastrointestinal (GI) symptoms (including anorexia, diarrhea, abdominal pain, bleeding, ulcerations, and perforation).…”