Heme oxygenase-1 as a predictor of sepsis-induced acute kidney injury: a cross-sectional study

Shilin Xia; Meishuai Zhang; Han Liu; Haibin Dong; Nannan Wu; Christian J Wiedermann; David Andaluz-Ojeda; Huiqing Chen; Nan Li

doi:10.21037/atm-22-4793

Heme oxygenase-1 as a predictor of sepsis-induced acute kidney injury: a cross-sectional study

Ann Transl Med. 2022 Nov;10(21):1177. doi: 10.21037/atm-22-4793.

Authors

Shilin Xia^#¹, Meishuai Zhang^#², Han Liu³, Haibin Dong⁴, Nannan Wu⁴, Christian J Wiedermann⁵, David Andaluz-Ojeda⁶, Huiqing Chen⁴, Nan Li⁴

Affiliations

¹ Clinical Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
² Emergency Department, Dalian University Affiliated Xinhua Hospital, Dalian, China.
³ Department of Oral Pathology, Dalian Medical University, Dalian, China.
⁴ Emergency Department, the First Affiliated Hospital of Dalian Medical University, Dalian, China.
⁵ Department of Public Health, Medical Decision Making and HTA, University of Health Sciences, Medical Informatics and Technology, Hall, Austria.
⁶ Intensive Care Unit Department, Hospital Universitario HM Sanchinarro, Hospitales Madrid, Madrid, Spain.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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.

Results: 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].

Conclusions: 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.

Keywords: Heme oxygenase-1 (HO-1); acute kidney injury (AKI); oxidative stress; sepsis.