Department of Medicine IV, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
Department of General and Digestive Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
PLoS One. 2021 May 11;16(5):e0249760. doi: 10.1371/journal.pone.0249760. eCollection 2021.
Acute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25-29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known.
We retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients.
In non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597).
Triple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.
急性肾损伤（AKI）是死亡的独立危险因素，约 5%的住院新型冠状病毒病 2019（COVID-19）患者和多达 25-29%的重症 COVID-19 患者会发生 AKI。洛匹那韦/利托那韦和羟氯喹对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）具有体外活性，并已用于 COVID-19 的治疗。洛匹那韦和羟氯喹均由细胞色素 P450（CYP）3A4 代谢。目前尚不清楚洛匹那韦/利托那韦和羟氯喹三联疗法（三联疗法）对 COVID-19 患者肾功能的影响。
我们回顾性分析了在德国弗赖堡大学医院住院的 COVID-19 接受三联疗法的非 ICU 和 ICU 患者 AKI 的发生率。接受标准治疗的患者作为对照组。所有患者均于 2020 年 3 月至 4 月在德国弗赖堡大学医院住院。对国家早期预警评分（NEWS）2 进行了配对分析，以控制非 ICU 患者的疾病严重程度。
非 ICU 患者接受三联疗法后 AKI 的发生率明显增加（78.6%比对照组 21.4%，p=0.002），而两组 ICU 患者 AKI 的发生率均较高（三联疗法：80.0%，对照组：90.5%）。接受三联疗法治疗的 ICU 患者表现为少尿或无尿性肾损伤的趋势。我们还观察到三联疗法的持续时间与血清肌酐最大值之间存在线性相关（p=0.004，R2=0.276，R=0.597）。
三联疗法与非 ICU COVID-19 患者 AKI 发生率增加相关。其潜在机制可能包括 CYP3A4 酶相互作用，并且可能与任何未来将羟氯喹与抗病毒药物联合使用的治疗方法相关。
