BACKGROUND & AIMS Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. We compared the changes of estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C virus (HCV) infection receiving SOF-based or SOF-free direct acting antivirals (DAAs). METHODS 481 patients with compensated liver diseases and eGFR ≥ 30 mL/min/1.73m2 receiving SOF-based (n = 308) or SOF-free (n = 173) DAAs for 12 weeks were prospectively enrolled. The eGFR was assessed from baseline to off-therapy week 24 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The eGFR evolutions between regimens were compared by generalized linear mixed-effects model (GLMM). Multivariate analysis was performed for factors affecting eGFR evolution. RESULTS Patients receiving SOF-based DAAs had a significant on-treatment eGFR decline (adjusted slope coefficient difference: -1.24 mL/min/1.73m2/month [95% CI: -1.35 to -1.13]; p < 0.001) and a significant off-therapy eGFR improvement (adjusted slope coefficient difference: 0.14 mL/min/1.73m2/month [95% CI: 0.08 to 0.21]; p = 0.004) than patients receiving SOF-free DAAs. Multivariate analysis showed age per 1-year increase (adjusted slope coefficient difference: -0.05 mL/min/1.73m2/month [95% CI: -0.05 to -0.04]; p < 0.001), SOF-based DAAs (adjusted slope coefficient difference: -0.33 mL/min/1.73m2/month [95% CI: -0.49 to -0.17]; p < 0.001), and CKD stage (adjusted slope coefficient difference: -1.44 mL/min/1.73m2/month [95% CI: -1.58 to -1.30] and -3.59 mL/min/1.73m2/month [95% CI: -3.88 to -3.30] for stage 3 and stage 2 vs. stage 1; p < 0.001) were independent factors affecting eGFR evolution from baseline to SVR24. CONCLUSIONS Patients receiving SOF-based DAAs have a quadratic trend with on-treatment worsening and off-therapy improving eGFR. Increasing age, SOF-based DAAs, and more advanced CKD stages are independently associated with eGFR decline in HCV patients receiving DAAs.

中文翻译：

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接受基于索非布韦或不含索非布韦的直接作用抗病毒药物的慢性 HCV 患者 eGFR 的演变

背景和目的 关于索非布韦 (SOF) 肾毒性的数据仍然存在争议。我们比较了接受基于 SOF 或不含 SOF 的直接作用抗病毒药物 (DAA) 的慢性丙型肝炎病毒 (HCV) 感染患者的估计肾小球滤过率 (eGFR) 的变化。方法 481 名代偿性肝病和 eGFR ≥ 30 mL/min/1.73m2 接受基于 SOF（n = 308）或无 SOF（n = 173）DAAs 治疗 12 周的患者被前瞻性纳入。通过慢性肾脏病流行病学合作 (CKD-EPI) 方程从基线到治疗结束第 24 周评估 eGFR。通过广义线性混合效应模型 (GLMM) 比较方案之间的 eGFR 演变。对影响 eGFR 演变的因素进行了多变量分析。结果 接受基于 SOF 的 DAA 的患者治疗后 eGFR 显着下降（调整后的斜率系数差异：-1.24 mL/min/1.73m2/月 [95% CI：-1.35 至 -1.13]；p < 0.001）并且显着降低治疗后 eGFR 改善（调整后的斜率系数差异：0.14 mL/min/1.73m2/月 [95% CI：0.08 至 0.21]；p = 0.004）与接受无 SOF 的 DAA 的患者相比。多变量分析显示每 1 年增加年龄（调整斜率系数差异：-0.05 mL/min/1.73m2/月 [95% CI：-0.05 至 -0.04]；p < 0.001），基于 SOF 的 DAA（调整斜率系数）差异：-0.33 mL/min/1.73m2/月 [95% CI：-0.49 至 -0.17]；p < 0.001）和 CKD 阶段（调整后的斜率系数差异：-1.44 mL/min/1.73m2/月 [95 % CI：-1.58 至 -1.30] 和 -3.59 mL/min/1.73m2/月 [95% CI：-3.88 至 -3.30] 对于第 3 阶段和第 2 阶段与第 1 阶段；p < 0.001) 是影响 eGFR 从基线到 SVR24 演变的独立因素。结论接受基于 SOF 的 DAA 的患者具有二次趋势，即治疗中恶化和治疗后 eGFR 改善。年龄增加、基于 SOF 的 DAA 和更晚期的 CKD 阶段与接受 DAA 的 HCV 患者的 eGFR 下降独立相关。