Abstract Background Chronic Hepatitis C virus (HCV) infection is associated with greater risk of chronic kidney disease and proteinuria. We examined effects of 12 weeks of elbasvir/grazoprevir, an HCV NS5A inhibitor/NS3/4A Protease Inhibitor on glomerular filtration (creatinine, cystatin C), injury (albuminuria), and 9 novel kidney tubule biomarkers in adults with HCV infection over a 24-week period.Figure.Percent Change (95% Confidence Interval) from Baseline of Urine Kidney Tubule Markers 24 weeks after initiating Elbasvir/Grazoprevir in Patients with HCV Methods We included 36 participants with HCV (7 with HIV coinfection) from the San Francisco Bay Area. Urine biomarkers included kidney tubule function (α-1-microglobulin [α1m], β-2-microglobulin [β2m]) and injury (kidney injury marker-1 [KIM-1], neutrophil gelatinase-associated lipocalcin [NGAL], (interleukin-18 [IL-18]), fibrosis/repair (monocyte chemoattractant protein 1 [MCP-1], chitinase-3-like protein-1 [YKL-40]) and synthetic function (epidermal growth factor [EGF], uromodulin [UMOD]). Biomarkers were measured at baseline, wk 12 (end of treatment), and week 24 (time of assessment for sustained virologic response [SVR]). We used linear mixed regression models with time as the main predictor to assess changes in kidney health, adjusting for demographics and urine creatinine. Results Over two thirds identified as Black/African American;89% were men and median age was 62 years. All but 2 achieved an SVR and 17% had advanced liver fibrosis using the FIB-4 serum marker. Median (interquartile range) for eGFRcr, eGFRcys, and urine albumin to creatinine ratio (ACR) were 82(63-100 ml/min),74(58-87 ml/min), and 10.4(4.9-24 mg/g), respectively at baseline. The percent (%) change from baseline for eGFRcr and ACR at weeks 12 and 24 was not statistically significant; eGFRcys was -11.4% lower (95%CI:-18%,-4.6%) at week 24. After 12 weeks of treatment, there were significant reductions in α1m, β2m, KIM-1, and MCP-1, with smaller reductions seen in most other markers (Figure). At week 24, these reductions were sustained for KIM-1. Conclusion Our findings suggest that HCV treatment with elbasvir/grazoprevir improves proximal tubule function and reduces cellular injury and fibrosis. Further research is needed to understand longer-term trends in kidney health following HCV cure. Disclosures Michelle Estrella, MD, Astra Zeneca: Board Member|Bayer: Grant/Research Support|Boehringer Ingelheim: Board Member Michael Shlipak, MD, Astra-Zeneca: Honoraria|Bayer: Grant/Research Support|Bayer: Honoraria|Boehringer Ingelheim: Honoraria Phyllis C. Tien, MD, MSc, Merck: Grant/Research Support
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