Contains all data used in the study.

IntroductionThe COVID-19 pandemic has been associated with significant variability in acute kidney injury (AKI) incidence, leading to concerns regarding patient heterogeneity. The study’s primary objective was a cluster analysis, to identify homogeneous subgroups of patients (clusters) using baseline characteristics, including inflammatory biomarkers. The secondary objectives were the comparisons of MAKE-90 and mortality between the different clusters at three months.MethodsThis retrospective single-center study was conducted in the Medical Intensive Care Unit of the University Hospital of Clermont-Ferrand, France. Baseline data, clinical and biological characteristics on ICU admission, and outcomes at day 90 were recorded. The primary outcome was the risk of major adverse kidney events at 90 days (MAKE-90). Clusters were determined using hierarchical clustering on principal components approach based on admission characteristics, biomarkers and serum values of immune dysfunction and kidney function.ResultsIt included consecutive adult patients admitted between March 20, 2020 and February 28, 2021 for severe COVID-19. A total of 149 patients were included in the study. Three clusters were identified of which two were fully described (cluster 3 comprising 2 patients). Cluster 1 comprised 122 patients with fewer organ dysfunctions, moderate immune dysfunction, and was associated with reduced mortality and a lower incidence of MAKE-90. Cluster 2 comprised 25 patients with greater disease severity, immune dysfunction, higher levels of suPAR and L-FABP/U Creat, and greater organ support requirement, incidence of AKI, day-90 mortality and MAKE-90.ConclusionsThis study identified two clusters of severe COVID-19 patients with distinct biological characteristics and renal event risks. Such clusters may help facilitate the identification of targeted populations for future clinical trials. Also, it may help to understand the significant variability in AKI incidence observed in COVID-19 patients.

引言
新型冠状病毒肺炎（COVID-19）大流行期间，急性肾损伤（AKI）的发生率存在显著异质性，由此引发了关于患者异质性的诸多担忧。本研究的首要目标为开展聚类分析，基于包括炎症生物标志物在内的基线特征，识别患者的同质亚组（聚类簇）；次要目标为对比不同聚类簇在3个月时的主要不良肾脏事件（MAKE-90）发生率与死亡率。

方法
本研究为回顾性单中心研究，于法国克莱蒙费朗大学医院内科重症监护病房开展。研究人员记录了患者入住重症监护病房（ICU）时的基线数据、临床及生物学特征，以及入住90天时的转归情况。本研究的主要结局为90天内主要不良肾脏事件（MAKE-90）的发生风险。聚类簇的确定采用基于入院特征、生物标志物以及免疫功能与肾功能血清学指标的主成分分层聚类法。

结果
本研究纳入了2020年3月20日至2021年2月28日期间因重型COVID-19入院的连续性成年患者，最终共纳入149例患者。研究共识别出3个聚类簇，其中2个聚类簇得到完整描述（第3簇仅包含2例患者）。第1簇包含122例患者，该亚组患者器官功能障碍程度较轻、免疫功能呈中度异常，其死亡率与MAKE-90发生率均较低。第2簇包含25例患者，该亚组患者疾病严重程度更高、免疫功能异常更显著，suPAR与L-FABP/U Creat水平更高，且器官支持需求、AKI发生率、90天死亡率与MAKE-90发生率均更高。

结论
本研究识别出两类具有独特生物学特征与肾脏事件发生风险的重型COVID-19患者聚类簇。此类聚类簇可助力未来临床试验中目标人群的精准筛选，同时也有助于解释COVID-19患者中AKI发生率的显著异质性。