Supplementary Material for: Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19

<b><i>Introduction:</i></b> Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. <b><i>Methods:</i></b> This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, β2 microglobulin and albumin levels pre/post-dialysis and on 1st–2nd week. We compared levels among both techniques and control group (HD without COVID-19). <b><i>Results:</i></b> We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and β2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. <b><i>Discussion:</i></b> Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. <b><i>Conclusion:</i></b> HDx appears to provide better clearance for TNFα and β2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

<b><i>引言：</i></b> 采用免疫抑制治疗改善重症新型冠状病毒肺炎（COVID-19）的核心靶点为控制细胞因子风暴。对于合并肾脏替代治疗（RRT）指征的COVID-19患者，有效的肾脏替代治疗可在细胞因子清除方面发挥优势。<b><i>方法：</i></b> 本研究为一项针对需接受血液透析（HD）的COVID-19患者的前瞻性观察性研究。研究对象根据布雷西亚（Brescia）团队的推荐方案，被分为在线血液透析滤过（OL-HDF）组与扩展型血液透析（HDx）组。我们分别于透析前后及第1~2周检测多种细胞因子、β2微球蛋白与白蛋白水平，并对比两组患者与对照组（无COVID-19的HD患者）的上述指标水平。<b><i>结果：</i></b> 本研究共纳入26例患者，其中18例为合并肾脏替代治疗的COVID-19患者（5例合并急性肾损伤[AKI]），8例为对照组患者。研究证实，COVID-19患者的细胞因子水平显著高于对照组，且合并AKI的患者细胞因子水平高于慢性肾脏病患者。除白细胞介素10（IL-10）与肿瘤坏死因子α（TNFα）外，多数细胞因子在HD治疗过程中水平升高。所有透析方式均可清除IL-10，而HDx组对TNFα的清除率更高。HDx可更充分地实现细胞因子水平正常化，并更显著地降低β2微球蛋白水平。OL-HDF组的病死率高于HDx组。<b><i>讨论：</i></b> 并非所有细胞因子在HD治疗过程中均表现出相同的变化规律。临床需考虑HD治疗过程中细胞因子的固有动力学特征等因素。HDx似乎可获得更优的治疗效果，这可能与多种因素的协同作用有关；但由于本研究样本量较小、存在脱落病例，且第二波疫情期间AKI发生率降低，本研究未达到统计学显著性差异。<b><i>结论：</i></b> HDx在HD治疗过程中可实现对TNFα与β2微球蛋白的更优清除，且与更低的病死率相关。鉴于HDx较OL-HDF更为安全有效，我们推荐将HDx技术应用于合并RRT指征的COVID-19患者。仍需开展进一步研究，但我们希望本研究的初步数据可为未来SARS-CoV-2或其他新发病毒引发的疫情防控提供参考。