Defining the Risks for Cytomegalovirus Infection and Disease After Solid Organ Transplantation

Abstract

Cytomegalovirus continues to be one of the most clinically significant infections after solid organ transplantation. Classic definitions of patients at high risk for infection and tissue-invasive disease are focused on recipient-donor serostatus, type of organ transplanted, and overall level of immunosuppression. However, recent trends in clinical practice call for a reevaluation of cytomegalovirus infection risks after solid organ transplantation. Indeed, whereas early-onset cytomegalovirus infection is usually controlled by antiviral prophylaxis with ganciclovir and derivatives, delayed- and late-onset cytomegalovirus infection can develop after the completion of a course of preventive therapy. In addition, indirect effects of cytomegalovirus infection may occur as a result of persistent low-level viremia. Suboptimal dosing of antiviral drugs due to specific drug toxicities may result in the development of ganciclovir-resistant cytomegalovirus disease. The relationship between organ allograft rejection and cytomegalovirus infection and disease has been recognized for some time. Transplantation of increasing numbers of extended-criteria donor organs increases the risk of delayed graft function and acute rejection, prompting the use of more intensive immunosuppression. In addition, the trend to spare long-term exposure to calcineurin inhibitors has contributed to a resurgence in the use of polyclonal T-cell induction immunosuppressive agents, which may reduce host anticytomegalovirus immunity. We discuss the current trends in solid organ transplantation that provide a foundation for defining risks for cytomegalovirus infection and disease, including identification of patients who would benefit from more aggressive cytomegalovirus monitoring and prevention strategies.

KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients

“…1 Patients at high risk for CMV replication and disease are seronegative individuals receiving an organ from a seropositive donor, or those receiving intensive and strongly T-cell-depleting immunosuppression, such as antithymocyte globulin (ATG). 2 Natural killer (NK) cells are of special interest in SOT, since studies have shown that these innate lymphocytes may be less susceptible to immunosuppressive agents such as calcineurin inhibitors. 3,4 In agreement with a role of NK cells in antiviral immunity after SOT, polymorphisms within the Killer cell Immunoglobulin-like Receptor (KIR) gene complex have been correlated with the risk of CMV replication after solid organ or hematopoietic stem cell transplantation.…”

Increased risk of breakthrough infection among cytomegalovirus donor‐positive/recipient‐negative kidney transplant recipients receiving lower‐dose valganciclovir prophylaxis

“…In kidney recipients, CMV is associated with direct effects, including CMV infection, disease, and end‐organ damage affecting the transplanted allograft, as well as indirect effects such as increased risk of rejection, Epstein–Barr virus‐associated post transplant lymphoproliferative disorder (PTLD), opportunistic infection, and malignancy . Risk factors for CMV infection include the net state of immunosuppression, the type of organ transplant, and donor/recipient serostatus . Given the significant risk for CMV‐related complications post transplant, universal prophylaxis is recommended for all high‐risk patients .…”

The role of belataceptin transplantation: results and implications of clinical trials in the context of other new biological immunosuppressant agents

“…Although primarily used for induction therapy, some agents have also been used in maintenance immunosuppression in some centers (Table ). They are, however, associated with an increased risk of infection, including cytomegalovirus (CMV) infection, and post‐transplant lymphoproliferative disorder (PTLD) . In addition, biologic agents based on non‐human proteins, such as OKT3, may induce antibody formation that limits their effectiveness .…”