Previous studies showed that extracellular histones could damage organs, but the role of extracellular histones in pneumonia patients with acute kidney injury (AKI) is unknown. This study aims to investigate the impact of extracellular histones on patients with community-acquired pneumonia (CAP) developed AKI. Blood samples were obtained within 24 h after admission to hospital from patients who were diagnosed with CAP. According to the discharge diagnosis, the patients were divided into 2 groups (Non-AKI and AKI). In vitro, A549 cells were treated with lipopolysaccharides (LPS) and conditioned media were collected. HK2 cells were exposed to the conditioned media or not. Cells proliferation and apoptosis of HK2 were determined. Clinically, Log₂ Histones (OR 3.068; 95% CI 1.544–6.097, P = 0.001) and estimated glomerular filtration rate (eGFR) (OR 0.945; 95% CI 0.914–0.978, P = 0.001) were predictors of AKI in CAP patients. Compared to the lower histones group, patients in the higher histones group were more likely to be admitted to ICU, receive mechanical ventilation, and have a longer length of in-hospital stay. In vitro, A549 cells injured by LPS released extracellular histones, in conditioned media which significantly promoted HK2 cells apoptosis. Extracellular histones was a high risk factor for developing AKI in CAP patients and a predictor of worse short-term outcomes. We also showed that extracellular histones in conditioned media damaged HK2 cells.

Trial registration number: KY20181102-03; Date of registration: 20181102.

先前的研究表明，细胞外组蛋白可能会损害器官，但细胞外组蛋白在急性肾损伤（AKI）肺炎患者中的作用尚不清楚。这项研究旨在调查细胞外组蛋白对社区获得性肺炎（CAP）引起的AKI患者的影响。入院后24小时内从确诊为CAP的患者那里采集血样。根据出院诊断，将患者分为2组（非AKI和AKI）。在体外，用脂多糖（LPS）处理A549细胞，并收集条件培养基。HK2细胞是否暴露于条件培养基。测定HK2的细胞增殖和凋亡。临床上，记录₂组蛋白（OR 3.068; 95％CI 1.544–6.097，P = 0.001）和估计的肾小球滤过率（eGFR）（OR 0.945; 95％CI 0.914-0.978，P  = 0.001）是CAP患者AKI的预测指标。与低组蛋白组相比，高组蛋白组的患者更有可能被送入ICU，接受机械通气，住院时间更长。在体外，LPS损伤的A549细胞在条件培养基中释放细胞外组蛋白，从而显着促进HK2细胞凋亡。细胞外组蛋白是CAP患者发生AKI的高风险因素，并且是短期预后较差的预测因素。我们还显示，条件培养基中的细胞外组蛋白会破坏HK2细胞。

试用注册号：KY20181102-03; 注册日期：20181102。