Valganciclovir Underdosing Is Associated With Cytomegalovirus DNAemia During Universal Prophylaxis: A Real‐Life Case Control Retrospective Study

Universal prophylaxis or a preemptive strategy with valganciclovir (VGCV) is recommended for prevention of cytomegalovirus (CMV) infections after kidney transplantation. We combined both strategies during the first 3 months post-transplantation. The objectives were to define the incidence of CMV DNAemia and identify the associated factors during universal prophylaxis in a retrospective monocentric case-control study. Cases presenting CMV DNAemia during the first 3 months post-transplantation were matched to four controls each regarding sex, age, donor and recipient CMV serostatus, and induction treatment. We collected the rates of visits with VGCV underdosing, comparing the adjusted daily dosage to the kidney function and the received daily dosage. Despite prophylaxis, the incidence of CMV DNAemia was 5.1% between 2017 and 2020 in 300 patients. Rates of visits with VGCV underdosing during follow-up were significantly higher in the cases group than in the controls group. In the cases group, the rate was higher when using estimated creatinine clearance rather than estimated glomerular filtration rate. VGCV underdosing was the only factor associated with CMV DNAemia in the multivariate analysis (OR: 1.04 95% CI: 1.011-1.061, p = 0.003), regardless of the formula used to estimate kidney function. Resistance to GCV was observed in 4 out of 15 cases, two of which had VGCV underdosing. In our study, CMV DNAemia was associated with VGCV underdosing that could be related to the absence of systematic adjustment during post-transplantation follow-up or to the use of inadequate kidney function assessment formulas to adjust VGCV dosages.