The Occurrence of Nephrotoxicity in Hepatitis C Patients Undergoing Sofosbuvir-Based Therapy

Abstract

Introduction: Sofosbuvir along with other NS5A inhibitors such as ledipasvir is drug of choice for the treatment of hepatitis C virus (HCV) infection. While highly effective in achieving sustained virologic response, interstitial nephritis has been reported with sofosbuvir and ledipasvir treatment. However, the occurrence of acute kidney injury (AKI) associated with sofosbuvir based treatment is unknown. Methods: A retrospective chart review of chronic HCV patients treated with sofosbuvir based therapy at our institution from 10/2014 to 11/2016 was performed. Patients over age 18 with at least 2 serum creatinine (sCr) measurements during sofosbuvir based treatment were included. Demographics, duration of therapy, and any available renal testing such as urinalysis, renal ultrasound, or biopsy were reviewed. AKI was defined as a rise in sCr of more than 0.3mg/dL. Individuals with a documented cause for AKI were excluded. Glomerular filtration rate (GFR) was estimated via the Modification of Diet in Renal Disease (MDRD) formula, and Pearson correlation analysis was performed. Results: A total of 435 patient records were reviewed. Thirty-four cases with no sCr measurements were excluded. Of the remaining 401 subjects, age was 64.5 ± 10.2 years, with 56.4% male and 88% infected with genotypes 1a/b. The mean treatment duration was 13.4 ± 4.3 weeks. Eighty-five (21.2%) had F4 fibrosis. The mean baseline sCr prior to treatment was 0.95 ± 0.22mg/dL, and mean eGFR 79.5mL/min per 1.73 m2. AKI was noted in 22 (5.5%) out of 401 patients during therapy, with an average sCr rise of 0.5 ± 0.2mg/dL. All but 2 of the 22 patients with AKI had their sCr return to baseline levels after treatment, and none required intervention or renal replacement therapy. The AKI group had an average of 1.9 weeks longer treatment duration. The magnitude of sCr increment in the group with AKI correlated with duration of treatment (r=0.45, p=0.03) but not with age, fibrosis stage or baseline sCr. Conclusion: We studied the occurrence of nephrotoxicity in HCV patients undergoing sofosbuvir based therapy. A small fraction of patients treated with this regimen developed AKI. Interestingly, a modest but statistically significant correlation between treatment duration and sCr increment suggests that sofosbuvir may be potentially causative. Monitoring of sCr in this clinical setting is recommended. Further investigations regarding the association between nephrotoxicity and sofosbuvir based therapy is needed.