Proteomics reveals biomarkers for sepsis-associated acute kidney injury: a prospective multicenter cohort study.
10.3760/cma.j.cn121430-20250317-00253
- Author:
Weimin ZHU
1
;
Nanjin CHEN
1
;
Hanzhi DAI
1
;
Cuicui DONG
1
;
Yubin XU
2
;
Qi CHEN
2
;
Fangyu YU
3
;
Cheng ZHENG
4
;
Chao ZHANG
5
,
6
;
Sheng ZHANG
1
;
Yinghe XU
1
;
Yongpo JIANG
1
Author Information
1. Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou 317000, China.
2. Precision Medicine Center, Taizhou Central Hospital, Taizhou University, Taizhou 318000, China.
3. Department of Intensive Care Unit, Taizhou Traditional Chinese Medicine Hospital, Taizhou 318000, China.
4. Department of Intensive Care Unit, Taizhou Municipal Hospital, Taizhou 318000, China.
5. Department of Intensive Care Unit, Taizhou Enze Hospital, Taizhou 318000, China. Corresponding author: Jiang Yongpo, Email: jyongpo8@
6. com.
- Publication Type:English Abstract
- MeSH:
Humans;
Sepsis/complications*;
Acute Kidney Injury/blood*;
Proteomics;
Prospective Studies;
Biomarkers/blood*;
Male;
Female;
beta 2-Microglobulin/blood*;
Middle Aged;
Cystatin C/blood*;
Aged
- From:
Chinese Critical Care Medicine
2025;37(8):707-714
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics.
METHODS:A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment.
RESULTS:A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β 2-microglobulin (β 2M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β 2M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β 2M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84.
CONCLUSIONS:Based on proteomic analysis, CST3, β 2M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
