Cytomegalovirus Exposure and the Risk of Overall Infection After Kidney Transplantation: A Cohort Study on the Indirect Effects Attributable to Viral Replication

Previous reports hypothesized that cytomegalovirus (CMV) may predispose to non-CMV infection after kidney transplantation (KT). We analysed the incidence of non-CMV infection (overall, bacterial and opportunistic) in 291 KT recipients according to the previous development of any level or high-level (≥1,000 IU/ml) CMV viremia. Exposure to CMV replication was assessed throughout fixed intervals covering first the 30, 90, 180 and 360 post-transplant days (cumulative exposure) and non-overlapping preceding periods (recent exposure). Adjusted Cox models were constructed for each landmark analysis. Overall, 67.7 and 50.5% patients experienced non-CMV and CMV infection, respectively. Patients with cumulative CMV exposure had higher incidence of non-CMV infection beyond days 30 (p-value = 0.002) and 90 (p-value = 0.068), although these associations did not remain after multivariable adjustment. No significant associations were observed for the remaining landmark models (including those based on high-level viremia or recent CMV exposure), or when bacterial and opportunistic infection were separately analysed. There were no differences in viral kinetics (peak CMV viremia and area under curve of CMV viral load) either. Our findings do not support the existence of an independent association between previous CMV exposure and the overall risk of post-transplant infection, although results might be affected by power limitations.