Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study.

The medium-term impact on graft function and immunosuppressive drug pharmacokinetics of direct antiviral agents (DAAs) among hepatitis C virus (HCV)-infected kidney transplant (KT) recipients remain unclear. We compared pre- and post-treatment 12-month trajectories of estimated glomerular filtration rate (ΔeGFR) and 24-h proteinuria (Δ24-h proteinuria) in 49 recipients treated with DAAs (mostly sofosbuvir plus ledipasvir). Among evaluable patients, 66.7% and 100.0% had undetectable viral load by week 4 and end of therapy (EoT). The sustained virologic response rate at 12 weeks was 95.8%. Overall, 80.6% of patients receiving tacrolimus required dose escalation while on DAA-based therapy (median increase of 66.7%) to maintain target levels. Tacrolimus levels resulted to be higher at 12 months compared to EoT (7.8 ± 2.1 vs. 6.7 ± 2.0 ng/ml; P-value = 0.002). No changes in graft function during the course of therapy were observed. However, eGFR significantly decreased (P-value <0.001) throughout the first 12 months after EoT. Median ΔeGFR and Δ24-h over pre- and post-treatment periods were 3.9% and -6.1% (P-value = 0.002) and -5.3% and 26.2% (P-value = 0.057). Caution should be exercised when adjusting immunosuppression in HCV-infected KT recipients upon initiation of DAAs, followed by mid-term monitoring of immunosuppressive drug levels and graft function.