Background: It is suggested that a low dose of valganciclovir can be equally
effective than a standard dose for cytomegalovirus (CMV) prophylaxis after kidney
transplantation. The aim of our study was to determine the ganciclovir exposure
observed under a routine daily dosage of 450 mg valganciclovir in kidney transplant
recipients with a wide range of renal function.
Methods: In this prospective study, kidney transplant recipients with a GFR MDRD
above 25 mL/min at risk for CMV (donor or recipient seropositive for CMV) received
a dose of valganciclovir (450 mg daily) prophylaxis for 3 months. Ganciclovir
levels at trough (Ctrough) and at peak (C3h) were measured monthly. Ganciclovir
exposure (AUC0-24) was estimated using Bayesian non-linear mixed-effect modelling
(NONMEM) and compared between 3 groups of patients according to their kidney
function: GFRMDRD 26-39 mL/min (Group 1), GFRMDRD 40-59 mL/min (Group 2)
and GFRMDRD 60-90 mL/min (Group 3). CMV DNAemia was assessed during and
after prophylaxis using PCR.
Results: Thirty-six patients received 450 mg daily of valganciclovir for 3 months.
Median ganciclovir C3h was 3.9 mg/L (range: 1.3-7.1) and Ctrough was 0.4 mg/L (range
0.1-2.7). Median (range) AUC0-24 of ganciclovir was 59.3 mg.h/L (39.0-85.3) in
Group 1 patients, 35.8 mg.h/L (24.9-55.8) in Group 2 patients and 29.6 mg.h/L (22.0-
43.2) in Group 3 patients (p<0.001). Anemia was more common in Group 1 patients
compared to patients on the other groups (p=0.01). No differences in other adverse
events according to ganciclovir exposure were observed. CMV DNAemia was not
detected during prophylaxis. After discontinuing prophylaxis, CMV DNAemia was
seen in 8/34 patients (23.5%) and 4/36 patients (11%) developed CMV disease.
Conclusion: A routine dosage of valganciclovir achieved plasma levels of ganciclovir
in patients with GFR>60 mL/min similar to those previously reported using oral
ganciclovir. A daily dose of 450 mg valganciclovir appears to be acceptable for
CMV prophylaxis in most kidney transplant recipients