Background and Aims: Renal toxicity of first generation protease inhibitors (IP) was not a safety signal in phase III clinical trials, until Mauss et al.’s report in Hepatology. Methods: We retrospectively analyzed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n =39) and a close monitoring of eGFR (MDRD formula) during and after treatment (D0, W4, 8, 12, 16, 24, 36, 48, 60, 72). Changes in eGFR over time were assessed by a linear mixed effects model (LMEM) with search for possible explanatory covariates. Results: Patients treated with telaprevir, presented a significant decrease of eGFR with the same kinetics: initial decrease at W4, nadir at W8 (mean decrease 17.0±18.9ml/min/1.73m2) and in average normalization at W16. The W8eGFR was highly correlated with the D0eGFR (R = 0.49) and was significantly lower in patients with grade II anemia or more (p = 0.031). The LMEM showed that the slope of eGFR versus time was the same for all patients and eGFR nadir could be predicted. In multivariate analysis, eGFR during the first 8 weeks was associated with time, older age, male sex and cryoglobulinemia. Conclusions: The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir was shown to inhibit mostly the human renal drug transporter OCT2 which interacts with creatinin transport, the early decrease of eGFR observed could be a benign phenomenom. However, as true and unpredictable renal toxicity may occur at any time during therapy, we recommend a thorough follow-up of eGFR.