Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management

Abstract

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.

The Best Method for CMV Prevention in High-risk Kidney Transplant Recipients? Either, per National Norwegian Transplant Database: Commentary on Blom et al, Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management

“…They measured weekly for 8 wks, and then monthly until a year after the transplant. As shown in Figure S1, 1 compliance with CMV DNAemia checks was impressively high for the first 3 mo, generally well >90% for D+R− and close to 90% for R+. Such diligent follow-up may not be possible in other programs, in which case prophylaxis may be a better choice than preemptive therapy.…”

“…This work by Blom et al 1 highlights the overall high rates of CMV infection even with the current best methods of prevention in the D+R− population (40% with prophylaxis, 64% with preemptive therapy), similar to what was seen with 100 d of prophylaxis in the IMPACT trial of D+R− kidney transplant recipients where 39% developed CMV disease (albeit with less routine monitoring than in this Norwegian work), although almost twice that seen with 200 d of prophylaxis in that trial at 21%. 9 This may reflect different criteria used to define infection.…”

“…It would be interesting to see further descriptions of viral kinetics in both populations. They did not see significant differences in outcomes including death, acute rejection, or graft loss in those recipients with higher levels of DNAemia (Figure S3 1 ).…”

“…In this issue of Transplantation , Blom et al publish a Norway-wide retrospective study of all adult cytomegalovirus (CMV) donor seropositive/recipient seronegative (D+/R−) and seropositive (R+) kidney transplant recipients conducted from 2007 until 2018 with follow-up through February 1, 2022. 1 Two thirds of all Norwegian kidney transplant recipients were included in this analysis, with all transplants done at a single center. During the first 4 y, D+/R− recipients were managed with preemptive therapy, then in 2011 prevention was switched to 6 mo of valganciclovir prophylaxis.…”

“…A significant number of patients developed “high-level CMV activity,” ranging from 29% of those on prophylaxis to 45% of those on preemptive therapy (Figure 2B 1 ). It is interesting that there was such a high rate of “high-level CMV activity” with close monitoring for those on preemptive therapy because it is commonly believed that infection may be caught in the early stages if we check CMV DNAemia once a week.…”