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Background: Following kidney transplantation (KT), cytomegalovirus (CMV) infection remains an important challenge. Both prophylactic and preemptive antiviral protocols are used for CMV high-risk kidney recipients (donor seropositive/recipient seronegative; D+/R-). We performed a nationwide comparison of the 2 strategies in de novo D+/R- KT recipients accessing long-term outcomes., Methods: A nationwide retrospective study was conducted from 2007 to 2018, with follow-up until February 1, 2022. All adult D+/R- and R+ KT recipients were included. During the first 4 y, D+/R- recipients were managed preemptively, changing to 6 mo of valganciclovir prophylaxis from 2011. To adjust for the 2 time eras, de novo intermediate-risk (R+) recipients, who received preemptive CMV therapy throughout the study period, served as longitudinal controls for possible confounders., Results: A total of 2198 KT recipients (D+/R-, n = 428; R+, n = 1770) were included with a median follow-up of 9.4 (range, 3.1-15.1) y. As expected, a greater proportion experienced a CMV infection in the preemptive era compared with the prophylactic era and with a shorter time from KT to CMV infection ( P  < 0.001). However, there were no differences in long-term outcomes such as patient death (47/146 [32%] versus 57/282 [20%]; P  = 0.3), graft loss (64/146 [44%] versus 71/282 [25%]; P  = 0.5), or death censored graft loss (26/146 [18%] versus 26/282 [9%]; P  = 0.9) in the preemptive versus prophylactic era. Long-term outcomes in R+ recipients showed no signs of sequential era-related bias., Conclusions: There were no significant differences in relevant long-term outcomes between preemptive and prophylactic CMV-preventive strategies in D+/R- kidney transplant recipients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

A series of prospective studies of a large cohort population of renal transplant recipients who did not receive cytomegalovirus (CMV) prophylaxis or preemptive therapy examined the effects of CMV infection and disease on renal allograft rejection, long-term recipient and graft survival, and new-onset diabetes mellitus. CMV infection and disease were found to be independent risk factors for allograft rejection and new-onset diabetes mellitus within 100 days posttransplantation, and for recipient mortality and uncensored graft loss beyond 100 days posttransplantation. Additional studies are needed to determine whether CMV prophylaxis or preemptive therapy may be of benefit in preventing these complications.