Bülow Anderberg Sara, Lipcsey Miklos, Hultström Michael, Eriksson Ann-Katrin, Venge Per, Frithiof Robert
Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, SE-751 85 Uppsala, Sweden.
Hedenstierna Laboratory, Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
J Clin Med. 2021 Sep 14;10(18):4144. doi: 10.3390/jcm10184144.
Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood (B-HNL). The latter after ex vivo activation with N-formyl-methionine-leucine-phenylalanine. All patients developed respiratory dysfunction and 62 (60%) were treated with invasive ventilation. Sixty-seven patients (65%) developed AKI, 18 (17%) progressed to AKI stage 3, and 14 (14%) were treated with continuous renal replacement therapy (CRRT). P-HNL Dimer was higher in patients with invasive ventilation, vasopressors, AKI, AKI stage 3, dialysis, and 30-day mortality ( < 0.001-0.046). B-HNL performed similarly with the exception of mild AKI and mortality ( < 0.001-0.004). The cohort was dichotomized by ROC estimated cutoff concentrations of 13.2 µg/L and 190 µg/L for P-HNL Dimer and B-HNL respectively. Increased cumulative risks for AKI, AKI stage 3, and death were observed if above the P-HNL cutoff and for AKI stage 3 if above the B-HNL cutoff. The relative risk of developing AKI stage 3 was nine and 39 times greater if above the cutoffs in plasma and whole blood, respectively, for CRRT eight times greater for both. In conclusion, systemically elevated neutrophil lipocalin, interpreted as increased neutrophil activity, was shown to be associated with an increased risk of severe AKI, renal replacement therapy, and mortality in COVID-19 patients with respiratory failure.
中性粒细胞被认为是新冠病毒疾病中器官功能障碍的介质。本研究调查了通过外周血中人中性粒细胞脂质运载蛋白（HNL）浓度估算的全身中性粒细胞活性是否与急性肾损伤（AKI）的发生相关。前瞻性纳入了103例入住重症监护病房、经聚合酶链反应确诊感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的成年患者（临床试验识别号：NCT04316884）。分析了血浆（P-HNL二聚体）和全血（B-HNL）中的HNL。全血在体外用N-甲酰甲硫氨酸-亮氨酸-苯丙氨酸激活后进行分析。所有患者均出现呼吸功能障碍，62例（60%）接受有创通气治疗。67例患者（65%）发生AKI，18例（17%）进展至AKI 3期，14例（14%）接受持续肾脏替代治疗（CRRT）。有创通气、使用血管升压药、发生AKI、AKI 3期、透析及30天死亡率的患者血浆中P-HNL二聚体水平更高（<0.001-0.046）。除轻度AKI和死亡率外，B-HNL的表现与之相似（<0.001-0.004）。根据受试者工作特征曲线（ROC）估计P-HNL二聚体和B-HNL的临界浓度分别为13.2μg/L和190μg/L，将队列分为两组。如果高于P-HNL临界值，则观察到AKI、AKI 3期和死亡的累积风险增加；如果高于B-HNL临界值，则观察到AKI 3期的累积风险增加。如果高于血浆和全血中的临界值，发生AKI 3期的相对风险分别高9倍和39倍，接受CRRT的相对风险两者均高8倍。总之，全身中性粒细胞脂质运载蛋白升高（被解释为中性粒细胞活性增加）与呼吸衰竭的新冠病毒疾病患者发生严重AKI、接受肾脏替代治疗及死亡的风险增加相关。
