Introduction: Cytomegalovirus (CMV) is the most common cause of viral infection among kidney transplant recipients. In immunocompromised patients, it is associated with increased morbidity, mortality, and reduced graft survival. In this study, we used the large Collaborative Transplant Study (CTS) database to evaluate factors that impact hospitalization due to CMV infection during the first year post-transplant. Additionally, we investigated the effects of CMV prophylaxis.
Method: We analyzed data from 10,933 adult recipients of kidney-only transplants from deceased donors between 2001 and 2020. Patients hospitalized due to CMV infection during first year post-transplant were compared to those without infection-related hospitalization. Kaplan-Meier analyses, multiple logistic regression, and multivariate Cox regression were implemented.
Results: Nearly half (45.4%) of our cohort consisted of CMV-positive recipients (R+) who received a transplant from a CMV-positive donor (D+). D–/R+ pairs accounted for 21.7%, while D+/R– combination comprised 19.1%. Only 13.9% of the transplants were D–/R–. Incidence of hospitalization due to CMV infection was 7.6% for D+/R+, 4.1% for D–/R+, 21.4% for D+/ R–, and 1.7% for D–/R– group.
Kaplan-Meier analysis showed significantly worse 5-year death-censored graft survival and increased mortality in patients who were hospitalized due to CMV infection in the first year post-transplant compared to those without infection-related hospitalization.

Multivariable Cox regressions confirmed these univariate analyses with significant hazard ratios of 2.2 for death-censored graft failure and of 1.6 for patient mortality. CMV-negative recipients receiving a kidney from a CMV-positive donor (D+/R–versus D–/R–) had an odds ratio of 13.1 (P<0.001) for CMV-related hospitalization.
Significant risk factors for hospitalization due to CMV, besides patient and donor CMV serostatus, were older donor age, treatment with Cyclosporin A versus Tacrolimus, induction with ATG versus no induction, female recipient, and marginal donor. On the other hand, CMV prophylaxis significantly reduced CMV-related hospitalization for all CMV-positive recipients, regardless of donor CMV status.

Conclusion: Our multicenter study confirms that hospitalization due to CMV infection has a detrimental effect on patient and death-censored graft survival. We identified significant risk factors that necessitate intensified post-transplant monitoring in specific patient subgroups. Additionally, our findings suggest that CMV prophylaxis significantly reduces the risk of hospitalized CMV infection during the first year post-transplant among CMV-positive recipients, irrespective of the donor CMV status.