title: Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Jianxin
authors: J
authors: Wan
authors: 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.
authors: Yanhong
authors: Y
authors: Wang
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Gaorong
authors: G
authors: Cai
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Jianbo
authors: J
authors: Liang
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Caifeng
authors: C
authors: Yue
authors: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Fen
authors: F
authors: Wang
authors: Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Junli
authors: J
authors: Song
authors: Institute of Laboratory Medicine, Guangdong Medical College, Dongguan, People's Republic of China.
authors: Jianfeng
authors: J
authors: Wang
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Min
authors: M
authors: Liu
authors: 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.
authors: Jinmei
authors: J
authors: Luo
authors: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Laisheng
authors: L
authors: Li
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000097:blood; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis; D012720:Severity of Illness Index; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: HE4; Pathology Section; biomarkers; diagnostic; kidney disease; renal fibrosis