Impact of kidney function on 200 days of antiviral prophylaxis for cytomegalovirus disease in cytomegalovirus-seronegative recipients of cytomegalovirus-seropositive donor kidneys: Post hoc analysis of a randomized, phase 3 trial of letermovir vs valganciclovir prophylaxis.
Budde, K., et al.Am J Transplant. 2025 Dec;25(12):2621-2633.
Aims
The aim of this study was to investigate how post-transplant kidney function affects 200-day cytomegalovirus (CMV) prophylaxis in high-risk cytomegalovirus-seronegative (R-) kidney transplant recipients (KTRs) with cytomegalovirus-seropositive donor (D+) kidneys.
Interventions
Participants in the original trial was randomised to either the letermovir group or the valganciclovir group.
Participants
601 adult CMV D+R- KTRs.
Outcomes
The main outcomes of interest wre kidney function (Cockcroft-Gault creatinine clearance [CrCl]), as well as prophylaxis dosing and adherence, quantifiable CMV DNAemia and CMV disease, and prophylaxis discontinuations in the CrCl population.
Follow-up
28 weeks
CET Conclusions
This paper presents a post hoc analysis of another, already published RCT. Valganciclovir and Letermovir were compared for CMV prophylaxis after renal transplantation from CMV+ donor to CMV- recipient. Letermovir was shown to be non-inferior to valganciclovir for CMV disease, but with less leukopenia. The present study focuses on the impact of variable kidney function, common after renal transplantation and how this interacts with the dosing and efficacy of both drugs. Valganciclovir dosing is dependent on renal function, whereas letermovir dosing is constant irrespective of current GFR, as it is hepatically eliminated. Discontinuation of medications was far higher in the valganciclovir group (17% versus 4%). Rates of CMV DNAemia were higher in the valganciclovir group when creatinine clearance was low (<67ml/min) but not significantly different if the creatinine clearance was high. The relative challenge of administering valganciclovir with varying renal function could be postulated to be related to the higher rates of CMV DNAemia when compared to a medication that does not need such adjustments. The study is well conducted, and the report convincing.
Trial registration
ClinicalTrials.gov - NCT03443869; MK-8228-002