Patients receiving SOF-based DAAs have a quadratic trend with on-treatment worsening and off-therapy improving eGFR. Patients receiving SOF-free DAAs have a linear trend with on-treatment and off-therapy improving eGFR. Increasing age, use of SOF-based DAAs, and baseline more advanced CKD stage are independent risk factors to be associated with eGFR decline in HCV patients receiving DAAs.