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Introduction: The role of Hepatitis C Virus (HCV) clearance in long-term kidney graft survival is unknown. In this study, we examined short-term trends of urinary protein/creatinine (P/C) ratios in a cohort of HCV-infected kidney transplant recipients with stable graft function and treated with direct-acting antivirals (DAAs). Methods: We conducted a retrospective study of 19 kidney transplant patients with chronic HCV infection treated with DAAs at the University of Alabama at Birmingham 1917 Viral Hepatitis Clinic between January 2013 and June 2016. Markers of glomerular damage were assessed using average protein/creatinine (P/C) ratios measured pre- and post-treatment. We also described treatment efficacy using sustained virologic response at 12 weeks post-HCV treatment (SVR12). Results: The median age of the 19 patients included was 59 years (Q1=58, Q3=64) at completion of treatment. Of these patients, 68% were African American, 32% were White and 63% were male. The median time between kidney transplant and initiation of DAA therapy was 2.25 years (Q1=0.79, Q3=3.79). Post-treatment P/C ratios (median=0.127, Q1=0.090, Q3=0.220) were significantly lower (p=0.01) than pre-treatment ratios (median=0.168, Q1=0.118, Q3=0.385). P/C ratios decreased in 14 of 19 patients (74%) with median change of -0.072 (median percent change= -40%). Post-treatment eGFRs (median=58.9, Q1=48.9, Q3=72.3) were not significantly different (p=0.82) than the pre-treatment values (median=57.0, Q1=48.8, Q3=67.8). Conclusions: In this preliminary study, there was a statistically significant decrease in P/C ratios associated with HCV clearance, suggesting a potential role for DAAs in improving kidney graft survival. Larger cohort studies will be needed to assess the clinical and long-term benefits of DAAs in this special population of HCV infected patients.

Background: Direct-acting antiviral (DAA) therapy among hepatitis C virus (HCV)-infected kidney transplant recipients is associated with short-term improvement in protein/creatinine (P/C) ratios, but how HCV cure affects long-term graft outcomes remains unknown. Methods: This is a retrospective follow-up study of 59 HCV-infected patients who underwent kidney transplant at the University of Alabama at Birmingham between 2007-2015 who were followed until the end of 2017. We examined the association of DAA-induced HCV cure with graft failure or death by survival analyses (Kaplan-Meier, Cox regression). Redsults: Mean age was 55 years, 73% were African American, and 68% were male. Median baseline creatinine was 1.4 mg/dL, P/C ratio was 0.5, and estimated glomerular filtration rate (eGFR) was 59 mL/min. Of those who received DAA, 24 (83%) achieved cure. The remaining 5 DAA patients (17%) did not have documented evidence of sustained virologic response (SVR). Overall, 19 (32%) patients experienced graft failure or death; with lower incidence in treated patients than untreated (4 vs 15 events; 2.6 vs 10.3 per 100 person-years [cHR 0.19, 95% CI: 0.06–0.66]). When adjusted for age, sex, race, and proteinuria, the association remained strong and invariant across time-varying (aHR 0.30, 95% CI: 0.08–1.10), time-averaged (aHR 0.28, 95% CI: 0.07–1.07), and time-varying-cumulative (aHR 0.32, 95% CI: 0.08–1.21) proteinuria metrics. Conclusions: DAAs therapy was associated with improved graft survival and reduced mortality. While not statistically significant, the association was strong, and these single-center findings warrant larger studies to demonstrate the benefits of HCV treatment in this population.