High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation

Abstract

BackgroundThe correct valganciclovir dose for cytomegalovirus (CMV) prophylaxis depends on renal function estimated by the Cockcroft–Gault (CG) estimated creatinine clearance (CG-CrCl) formula. Patients with delayed or rapidly changing graft function after transplantation (tx) will need dose adjustments.MethodsWe performed a retrospective investigation of valganciclovir dosing in renal transplant patients receiving CMV prophylaxis between August 2003 and August 2011, and analysed valganciclovir dosing, CG-CrCl, CMV viraemia (CMV-PCR <750 copies/mL), leucopenia (<3500/µL) and neutropenia (<1500/µL) in the first year post-transplant. On Days 30 and 60 post-transplant, dosing pattern in relation to estimated creatinine clearance was analysed regarding CMV viraemia, leucopenia and neutropenia.ResultsSix hundred and thirty-five patients received valganciclovir prophylaxis that lasted 129 ± 68 days with a mean dose of 248 ± 152 mg/day of whom 112/635 (17.7%) developed CMV viraemia, 166/635 (26.1%) leucopenia and 48/635 (7.6%) neutropenia. CMV resistance within 1 year post-transplant was detected in three patients. Only 137/609 (22.6%) patients received the recommended dose, while n = 426 (70.3%) were underdosed and n = 43 (7.1%) were overdosed at Day 30 post-tx. Risk factors for CMV viraemia were donor positive D (+)/receptor negative R (−) status and short prophylaxis duration, but not low valganciclovir dose. Risk factors for developing leucopenia were D+/R− status and low renal function. No significant differences in dosing frequency were observed in patients developing neutropenia or not (P = 0.584).ConclusionMost patients do not receive the recommended valganciclovir dose. Despite obvious underdosing in a large proportion of patients, effective prophylaxis was maintained and it was not associated as a risk factor for CMV viraemia or leucopenia.

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

“…23,24,[28][29][30][31][32] Moreover, our study design is closer to clinical reality, with similar valganciclovir doses and prophylaxis duration to those routinely employed in the clinic. 53 Based on the limitations and advantages of the study, we deem our results as evidence that further research is needed to determine the effects of prevention strategies on transplantation outcome and their hypothetical interactions with sex.…”

Outcomes among CMV‐mismatched and highly sensitized kidney transplants recipients who develop neutropenia

“…Other studies have shown that changes in MPA lead to more rejection and decreased graft survival 3,7,20,23 and changes in valganciclovir lead to more CMV viremia. 8,24 We found that neutropenia was associated with more rejection which may be mediated by MPA dose reductions or discontinuations. We also observed high rates of G-CSF use; neutropenia was associated with a 40-fold increase in G-CSF use.…”

Low-Dose Valganciclovir Prophylaxis Is Safe and Cost-Saving in CMV-Seropositive Kidney Transplant Recipients

“…Fourth, we did not collect data on acute graft rejection or changes in maintenance immunosuppression. Last, because of the overlap in dosing for patients with CrCl between 40 and 60 mL/min, and relatively frequent VGC underdosing early after transplant, 27 some patients in the SD-VGC group may have received the same dose as indicated by the LD-VGC protocol, which we tried to account for in the potential medication cost comparison. Αlthough some of these limitations and relative imbalances (eg higher percentage of D+ patients in the SD-VGC group) may explain a trend for lower incidence of CMV DNAemia in the LD group, it is highly unlikely they would mask a benefit from SD-VGC.…”