Research Papers: Pathology:
Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease
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Jianxin Wan1,*, Yanhong Wang2,*, Gaorong Cai1,*, Jianbo Liang1, Caifeng Yue1, Fen Wang3, Junli Song4, Jianfeng Wang5, Min Liu1, Jinmei Luo2 and Laisheng Li1
1 Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
2 Department of Internal Medicine, Medical Intensive Care Unit and Division of Respiratory Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
3 Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
4 Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
5 Institute of Laboratory Medicine, Guangdong Medical College, Dongguan, People’s Republic of China
* These authors have contributed equally to this work
Laisheng Li, email:
Jinmei Luo, email:
Keywords: HE4; diagnostic; renal fibrosis; kidney disease; biomarkers; Pathology Section
Received: June 16, 2016 Accepted: August 26, 2016 Published: August 29, 2016
Background: Human epididymis protein 4 (HE4), has recently been reported as a mediator of renal fibrosis. However, serum HE4 levels appear in a large number of patient samples with chronic kidney disease (CKD), and the relationship of these levels to disease severity and renal fibrosis is unknown.
Methods: In 427 patients at different stages of CKD excluding gynecologic cancer and 173 healthy subjects, serum HE4 concentrations were tested by chemiluminescent microparticle immunoassay. Renal biopsy was performed on 259 of 427 subjects. Histological findings were evaluated using standard immunohistochemistry.
Results: The levels of serum HE4 were higher in CKD patients than in healthy subjects, and higher levels were associated with more severe CKD stages. Patients with more severe renal fibrosis tended to have higher HE4 levels, and correlation analysis showed a significant correlation between HE4 and degree of renal fibrosis (r = 0.938, P < 0.0001). HE4 can be a predictor of renal fibrosis in CKD patients; the area under the receiver-operating characteristic curve (AUC-ROC) was 0.99, higher than the AUC-ROC of serum creatinine (0.89).
Conclusion: Elevated levels of serum HE4 are associated with decreased kidney function, and also with an advanced stage of renal fibrosis, suggesting that HE4 may serve as a valuable clinical biomarker for renal fibrosis of CKD.
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