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Background: Direct-acting antivirals (DAAs) have significantly improved the efficacy and safety of treating chronic hepatitis C (CHC), but their effectiveness and safety among patients with chronic kidney disease (CKD) remains poorly understood. Sofosbuvir/daclatasvir regimen is supposed to be used for patients with creatinine clearance more than 30 mL/min, while ombitasvir/paritaprevir/ritonavir regimen is used for patients with creatinine clearance less than 30 mL/min., Aim: The aim of the study was to assess the safety and efficacy of DAAs among patients with CKD., Methods: Eighteen CKD stage 2-3b patients received sofosbuvir for 3 months. In addition, 42 CKD stage-4 patients received ritonavir-boosted paritaprevir plus ombitasvir for 3 months. Finally, ribavirin was added for 30 of them., Results: The patients'age was 49.2 ± 12 years. Baseline serum creatinine was 3.76 ± 1.67 mg/dL. Fifty patients were HCV genotype 4. A 3-month sustained viral response was achieved in 56 patients and 49 patients achieved a 6-month viral response. There were 11 relapsers. Acute kidney injury (AKI) upon CKD (AKI/CKD) occurred in 28 patients, of which 20 needed hemodialysis. Fifteen/28 recovered from AKI, whereas 13 were maintained on hemodialysis. In multivariate analysis, there were only two independent risk factors for developing AKI/CKD, i.e., being cirrhotic as defined by baseline abdominal ultrasound findings [odds ratio 4.15 (1.33-12.97); p = 0.013] and having had as DAA therapy OMV/PTV/RTV [odds ratio 7.35 (1.84-29.35); p = 0.001]., Conclusion: Treatment of HCV among stage 2, 3a, and 3b patients was achieved safely with a sofosbuvir-based regimen. We recommend that stage-4 patients wait until starting hemodialysis or transplantation.