Abstract
Background
Cytomegalovirus (CMV) is a common pathogen in kidney transplant recipients (KTRs). KTRs may develop CMV viremia that is asymptomatic (‘CMV infection’) or associated with clinical and laboratory findings (‘CMV disease’) such as fever, leukopenia/neutropenia, and malaise (‘CMV syndrome’), and/or evidence of specific organ(s) involvement (‘CMV end-organ disease’). The extent to which CMV affects morbidity such as acute rejection (AR), graft loss (GL), other opportunistic infections (OI), or mortality in KTRs has not been systematically evaluated recently. Therefore, we examined the association between CMV infection/disease and morbidity and mortality in KTRs using a systematic review of observational studies from the last decade.
Methods
MEDLINE and Embase were searched to identify observational studies published between January 2008 and November 2018 reporting outcomes of interest by CMV status. Meta-analysis was used to derive pooled odds ratio (pOR) with 95% confidence intervals(CIs) using the random-effects models and I2 statistics to estimate heterogeneity between studies using R version 3.5.1.
Results
Of 1,860 retrieved citations, 23 studies with a total of 6,994 KTRs met inclusion criteria. The majority of studies were conducted in Europe (N=14) and included participants regardless of donor/recipient CMV serostatus (N=14). Included studies reported outcomes by different clinical manifestations of CMV. Overall, CMV infection/disease was associated with an increased odd of AR, with significant heterogeneity. CMV infection/disease was also associated with an increase in the odds of GL and mortality compared to no CMV infection/disease without heterogeneity (Figure 1). A higher rate of all-cause hospital readmission and a greater mean number of OI episodes were reported with CMV infection/disease in a single study.
Pooled Estimates on the Association between Outcomes and CMV Infection/Disease among Individuals undergoing Kidney Transplant
Conclusion
CMV infection/disease was associated with increased mortality and GL in adults with KT. The association between CMV and AR remained similar in direction with high heterogeneity limiting the robustness of the conclusion. Nonetheless, our analysis underscores the importance of interventions to reduce the incidence of CMV infection/disease to reduce mortality and GL in KTRs even in the current era.
Disclosures
Amit D. Raval, PhD, Merck and Co., Inc (Employee) Kristin Kistler, PhD, Evidera, Inc. (Employee, Evidera, Inc. received the funding to conduct this study.) Yuexin Tang, PhD, Merck and Co., Inc. (Employee) Yoshihiko Murata, MD, PhD, Merck and Co., Inc. (Employee) David R. Snydman, MD, Merck (Consultant)Merck (Advisor or Review Panel member)Pfizer (Consultant)Reviral, Anthrax Vaccine, Influenza Vaccine (Other Financial or Material Support, Data Safety Monitoring Board)Takeda/Shire (Advisor or Review Panel member)
Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention
