The use of Tocilizumab in COVID-19 critically ill patients with renal impairment: a multicenter, cohort study

Tocilizumab (TCZ) is recommended in patients with COVID-19 who require oxygen therapy or ventilatory support. Despite the wide use of TCZ, little is known about its safety and effectiveness in patients with COVID-19 and renal impairment. Therefore, this study evaluated the safety and effectiveness of TCZ in critically ill patients with COVID-19 and renal impairment. A multicenter retrospective cohort study included all adult COVID-19 patients with renal impairment (eGFR˂60 mL/min) admitted to the ICUs between March 2020 and July 2021. Patients were categorized into two groups based on TCZ use (Control vs. TCZ). The primary endpoint was the development of acute kidney injury (AKI) during ICU stay. We screened 1599 patients for eligibility; 394 patients were eligible, and 225 patients were included after PS matching (1:2 ratio); there were 75 TCZ-treated subjects and 150 controls. The rate of AKI was higher in the TCZ group compared with the control group (72.2% versus 57.4%; <i>p</i> = 0.03; OR: 1.83; 95% CI: 1.01, 3.34; <i>p</i> = 0.04). Additionally, the ICU length of stay was significantly longer in patients who received TCZ (17.5 days versus 12.5 days; <i>p</i> = 0.006, Beta coefficient: 0.30 days, 95% CI: 0.09, 0.50; <i>p</i> = 0.005). On the other hand, the 30-day and in-hospital mortality were lower in patients who received TCZ compared to the control group (HR: 0.45, 95% CI: 0.27, 0.73; <i>p</i> = 0.01 and HR: 0.63, 95% CI: 0.41, 0.96; <i>p</i> = 0.03, respectively). The use of TCZ in this population was associated with a statistically significantly higher rate of AKI while improving the overall survival on the other hand. Further research is needed to assess the risks and benefits of TCZ treatment in critically ill COVID-19 patients with renal impairment.

托珠单抗（Tocilizumab，TCZ）被推荐用于需要氧疗或呼吸支持的新型冠状病毒肺炎（COVID-19）患者。尽管TCZ的临床应用已十分广泛，但目前对其在合并肾功能损害的新冠患者中的安全性与有效性仍知之甚少。为此，本研究评估了TCZ在合并肾功能损害的重症新冠患者中的安全性与有效性。本研究为多中心回顾性队列研究，纳入了2020年3月至2021年7月期间入住重症监护病房（ICU）、合并肾功能损害[估算肾小球滤过率（estimated glomerular filtration rate，eGFR）<60 mL/min]的所有成年新冠患者。根据是否使用TCZ将患者分为两组：对照组与TCZ治疗组。本研究的主要终点为患者入住ICU期间急性肾损伤（acute kidney injury，AKI）的发生情况。本研究共筛查1599例患者以评估入组资格，最终394例患者符合入组标准，经倾向性评分匹配（propensity score matching，PS匹配，1:2比例）后共纳入225例患者，其中TCZ治疗组75例，对照组150例。结果显示，TCZ治疗组患者的AKI发生率显著高于对照组（72.2% vs 57.4%；p=0.03；比值比（odds ratio，OR）=1.83；95%置信区间（confidence interval，CI）：1.01~3.34；p=0.04）。此外，TCZ治疗组患者的ICU住院时长显著更长（17.5天 vs 12.5天；p=0.006，β系数=0.30天；95%CI：0.09~0.50；p=0.005）。另一方面，与对照组相比，TCZ治疗组患者的30天死亡率与住院总死亡率均更低（风险比（hazard ratio，HR）=0.45，95%CI：0.27~0.73；p=0.01；HR=0.63，95%CI：0.41~0.96；p=0.03）。综上，在该人群中使用TCZ与AKI发生率的统计学显著升高相关，但同时可改善患者的总体生存率。未来仍需开展进一步研究，以评估TCZ治疗合并肾功能损害的重症新冠患者的风险与获益。