The incidence of cytomegalovirus and BK polyomavirus infections in kidney transplant patients receiving mTOR inhibitors: A systematic review and meta-analysis

Abstract

Cytomegalovirus (CMV) and BK polyomavirus (BKPyV) infections after kidney transplant have become increasingly prevalent. Based on previous studies, the mammalian target of rapamycin (mTOR) inhibitors seem like attractive alternatives with antiviral activity. The objective of this systematic review and meta-analysis was to investigate the incidence of CMV and BKPyV infections in kidney transplantation recipients receiving mTOR inhibitors. This meta-analysis included three comparisons of immunosuppressant regimens commonly used after kidney transplantation: Comparison 1: mTOR inhibitors versus calcineurin inhibitors (CNI); Comparison 2: mTOR inhibitors versus antimetabolites (AM); and Comparison 3: mTOR inhibitors plus a reduced-dose of CNI versus AM plus a standard-dose of CNI. The group containing mTOR inhibitors was the study group and the remaining one was the control group. The incidence of CMV or BKPyV infection defined by positive culture, serology, or polymerase chain reaction testing was the primary outcome. A total of 61 studies involving 13,609 patients were included. As compared with the control group, a significantly decreased risk of CMV and BKPyV infections favoring the mTOR inhibitors-based group was shown in comparisons 1, 2, and 3 (p < 0.05). Compared with the control group in all three comparisons, mTOR inhibitors made no difference in regard to death and graft loss (p > 0.05). Compared with CNI, the incidence of biopsy-proven acute rejection (BPAR) and anemia was higher with mTOR inhibitors (p < 0.05). In comparisons 2 and 3, the risk of new-onset diabetes mellitus (NODM) was higher with mTOR inhibitors (p < 0.05). Early introduction of mTOR inhibitors reduced more CMV infections in comparisons 1 and 2 (p < 0.05). The mTOR inhibitor-based regimen is an attractive alternative with lower risk of CMV and BKPyV infections in kidney transplant recipients. The combination regimen is more appropriate and acceptable than the mTOR-inhibitor monotherapy-based regimen. Early introduction of mTOR inhibitors is recommended, although it is worth noting that attention should be paid to wound healing when mTOR inhibitors are introduced early.

Keywords: BK polyomavirus infection; cytomegalovirus infection; kidney transplant; mammalian target of rapamycin inhibitors.