Xia Shilin, Zhang Meishuai, Liu Han, Dong Haibin, Wu Nannan, Wiedermann Christian J, Andaluz-Ojeda David, Chen Huiqing, Li Nan
Clinical Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
Emergency Department, Dalian University Affiliated Xinhua Hospital, Dalian, China.
Ann Transl Med. 2022 Nov;10(21):1177. doi: 10.21037/atm-22-4793.
Sepsis patients suffer from severe inflammation and poor prognosis. Oxidative stress and local inflammation that results from sepsis can trigger organ injury, including acute kidney injury (AKI). Previous studies have shown that heme oxygenase-1 (HO-1) is overexpressed in proximal tubular cells under oxidative stress and has significant cytoprotective and anti-inflammatory effects. Heme-induced inflammation in sepsis is antagonized by increased tissue expression of heme oxygenase-1 (HO-1), which impacts on AKI development. The investigators observed intrarenal HO-1 expression and corresponding potential increases in plasma and urinary HO-1 protein concentrations in four different AKI models. Since serum levels of HO-1 reflect HO-1 expression, we aimed to investigate whether serum HO-1 could predict the development of AKI in sepsis patient.
A total of 83 sepsis patients were enrolled in this study including septic patients with AKI and sepsis patients without AKI. According to the definition of septic shock and the global kidney diagnostic criteria described in the Kidney Disease: Improving Global Outcomes (KDIGO), patients were allocated to the sepsis and septic shock groups with and without AKI, respectively. The serum levels of HO-1 were measured by enzyme-linked immunosorbent assays (ELISA). Statistical analyses were performed using SPSS software.
There were statistically significant differences between septic patients with AKI and sepsis patients without AKI in terms of Sequential Organ Failure Assessment (SOFA) score, hospitalization time, and laboratory indicators including serum HO-1, creatine kinase MB (CK-MB), troponin I (TnI), urea, myoglobin (MYO), serum creatinine (Scr), procalcitonin, and activated partial thromboplastin time. Serum levels of alkaline phosphatase (ALP), urea, MYO, Scr, procalcitonin, activated partial thromboplastin time, and prothrombin time exhibited significant differences among the four groups. The concentration of serum HO-1 was higher in sepsis-induced AKI compared with sepsis patients without AKI. Serum HO-1 levels were increased in patients with sepsis shock-induced AKI. The area under the receiver operating characteristic (ROC) curve for serum HO-1 combined with Scr was 0.885 [95% confidence interval (CI): 0.761-1.000].
Serum HO-1 is positively correlated with sepsis-induced AKI. These findings suggest that measurement of serum HO-1 may play a diagnostic and prediction role in sepsis-induced AKI.
脓毒症患者存在严重炎症反应且预后较差。脓毒症引发的氧化应激和局部炎症可导致器官损伤，包括急性肾损伤（AKI）。既往研究表明，在氧化应激状态下，近端肾小管细胞中的血红素加氧酶-1（HO-1）过度表达，具有显著的细胞保护和抗炎作用。血红素加氧酶-1（HO-1）组织表达增加可拮抗脓毒症中血红素诱导的炎症，这会影响急性肾损伤的发生发展。研究人员在四种不同的急性肾损伤模型中观察了肾内HO-1表达以及血浆和尿液中HO-1蛋白浓度相应的潜在升高情况。由于血清中HO-1水平反映HO-1表达情况，我们旨在研究血清HO-1是否可预测脓毒症患者急性肾损伤的发生。
本研究共纳入83例脓毒症患者，包括合并急性肾损伤的脓毒症患者和未合并急性肾损伤的脓毒症患者。根据脓毒症休克的定义以及《改善全球肾脏病预后组织（KDIGO）》中描述的全球肾脏诊断标准，患者分别被分配至合并或未合并急性肾损伤的脓毒症组和脓毒症休克组。采用酶联免疫吸附测定（ELISA）法检测血清HO-1水平。使用SPSS软件进行统计分析。
合并急性肾损伤的脓毒症患者与未合并急性肾损伤的脓毒症患者在序贯器官衰竭评估（SOFA）评分、住院时间以及包括血清HO-1、肌酸激酶同工酶MB（CK-MB）、肌钙蛋白I（TnI）、尿素、肌红蛋白（MYO）、血清肌酐（Scr）、降钙素原和活化部分凝血活酶时间等实验室指标方面存在统计学显著差异。碱性磷酸酶（ALP）、尿素、MYO、Scr、降钙素原、活化部分凝血活酶时间和凝血酶原时间的血清水平在四组之间存在显著差异。与未合并急性肾损伤的脓毒症患者相比，脓毒症诱导的急性肾损伤患者血清HO-1浓度更高脓毒症休克诱导的急性肾损伤患者血清HO-1水平升高。血清HO-1联合Scr的受试者工作特征（ROC）曲线下面积为0.885[95%置信区间（CI）：0.761 - 1.000]。
血清HO-1与脓毒症诱导的急性肾损伤呈正相关。这些发现表明，检测血清HO-1可能在脓毒症诱导的急性肾损伤中发挥诊断和预测作用。
