Title: Time to Cytomegalovirus Viremia After Valganciclovir Discontinuation in Intermediate and High-Risk Kidney Transplant Recipients
Authors: Morgan Pickard, Kwame Asare, Caren Azurin, Taylor Nickens
Objective: Duration from valganciclovir discontinuation to cytomegalovirus viremia in intermediate and high-risk kidney transplant recipients
Self Assessment Question: Does valganciclovir discontinuation impact time to CMV viremia in intermediate and high-risk kidney transplant recipients?
Background: Cytomegalovirus (CMV) infection is the most common opportunistic infection following solid organ transplantation, particularly affecting transplant recipients at intermediate (INT) (recipient positive) and high-risk (donor positive, recipient negative) for CMV reactivation. Reactivation can lead to serious complications such as tissue invasion and increased risk of rejection, opportunistic infection, and mortality. Valganciclovir (VGCV) is guideline approved for prophylaxis in these two groups, but its use can be limited by adverse effects such as leukopenia, which occurs in about 50% of patients. Despite the widespread use of VGCV, there is limited research examining whether the duration from VGCV discontinuation to CMV viremia varies between INT and high-risk kidney transplant recipients. This study aimed to evaluate if there is a difference in the mean duration from VGCV discontinuation to CMV viremia between these two groups.
Methods: This single-center retrospective chart review utilized electronic medical records and organ transplant tracking record (OTTR) software at Ascension Saint Thomas Hospital West (ASTHW), with data collected from March 2018 to April 2024. Kidney transplant recipients were identified via OTTR, and data from INT and high-risk groups were analyzed. Patients were categorized into INT and high-risk groups and screened for eligibility based on inclusion/exclusion criteria. Eligible participants were adults (≥ 18 years) who received a kidney transplant, were at INT or high-risk for CMV, discontinued VGCV, and developed CMV viremia. Exclusion criteria included dual organ transplants, pregnancy, incarceration, and restarting VGCV after rejection. The primary outcome assessed the difference in the mean duration from VGCV discontinuation to CMV viremia between the two groups. Secondary outcomes included rejection rates, readmission, resistant CMV, and bacterial, viral, or fungal infections after CMV viremia.
Results: A total of 202 patients were included, with 147 in the INT-risk and 55 in the high-risk groups. CMV viremia developed in 1 (6%) INT and 6 (43%) high-risk patients following VGCV discontinuation during the prophylactic period (p = 0.018). There were no significant differences in the duration of VGCV discontinuation to CMV viremia (42 vs. 43 days, p = 0.999). Additionally, there were no significant differences between the groups in rejection rates (0% vs. 0%, p = 0.999), readmission rates (100% vs. 50%, p = 0.999), infection rates (0% vs. 0%, p = 0.999), and resistant CMV rates (0% vs. 17%, p = 0.999). However, CMV developed in 37 (25%) INT and 12 (24%) high-risk individuals within 3 months following prophylaxis. The time from VGCV discontinuation to CMV viremia during this time was significant between the groups (56 vs. 36 days, p = 0.021). The average interval between CMV tests was also significant (21 vs. 12 days, p < 0.0001).
Results: A total of 202 patients were included, with 147 in the INT-risk and 55 in the high-risk groups. CMV viremia developed in 1 (6%) INT and 6 (43%) high-risk patients following VGCV discontinuation during the prophylactic period (p = 0.018). There were no significant differences in the duration of VGCV discontinuation to CMV viremia (42 vs. 43 days, p = 0.999). Additionally, there were no significant differences between the groups in rejection rates (0% vs. 0%, p = 0.999), readmission rates (100% vs. 50%, p = 0.999), infection rates (0% vs. 0%, p = 0.999), and resistant CMV rates (0% vs. 17%, p = 0.999). However, CMV developed in 37 (25%) INT and 12 (24%) high-risk individuals within 3 months following prophylaxis. The time from VGCV discontinuation to CMV viremia during this time was significant between the groups (56 vs. 36 days, p = 0.021). The average interval between CMV tests was also significant (21 vs. 12 days, p < 0.0001).
Conclusion: No significant differences were found in the time from VGCV discontinuation to CMV viremia, or in rejection, readmission, infection, or resistant CMV rates during the prophylactic period. However, our study found that stopping prophylactic VGCV increases CMV risk, especially in the high-risk group. CMV was common in the first three months post-prophylaxis. We recommend CMV monitoring every 14 days during this period.
