title: Urinary heme oxygenase-1 as a potential biomarker for early diabetic nephropathy.
abstract: BACKGROUND
  Our previous study showed that increases of urinary heme oxygenase-1 (uHO-1) could be a potential biomarker indicating evaluating intrarenal oxidative damage in obstructive nephropathy. Activation of oxidative stress is an important mediator of diabetic nephropathy (DN). The aim of this study was to investigate the clinical implications of uHO-1 levels in patients with type 2 diabetes.
  
  
  METHODS
  Eighty-four type 2 diabetic patients with normoalbuminuria (n=28), microalbuminuria (n=28), and macroalbuminuria (n=28) were included in this study. Control samples were collected from healthy volunteers (n=28) who had normal albuminuria and renal function. Urine HO-1 levels were evaluated by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Urinary HO-1/creatinine (cr.) levels were significantly elevated in diabetic patients with microalbuminuria and macroalbuminuria compared to those in diabetic patients with normoalbuminuria (P<0.001) and control subjects (all P<0.001). In diabetic patients with normoalbuminuria, uHO-1/cr. levels were also higher than those in controls (P<0.001). Multivariate regression analyses revealed that uHO-1/cr. levels were positively correlated to urinary albumin/creatinine ratio and inversely correlated to glomerular filtration rate. Receiver operating characteristic (ROC) curve analysis of uHO-1/cr. levels for early diagnosis and detection of DN revealed that the cut-off value of uHO-1/cr. was 4.59 ng/mg (sensitivity 75%, specificity 78.6%).
  
  
  CONCLUSIONS
  The findings of this study indicate that increases of urine HO-1 levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria, and associated with renal derangement in patients with established diabetic nephropathy. Urinary HO-1 may be used as an early biomarker for diabetic renal injury.
authors.affiliation: Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Nephrology, the People's Hospital of Hebi, Hebi, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Experimental Pathology, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Zhanzheng
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000419:Albuminuria / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004796:Clinical Enzyme Tests; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051547:Heme Oxygenase-1 / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D015854:Up-Regulation; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D003404:Creatinine; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Biomarker; Diabetic nephropathy; Heme oxygenase-1; Oxidative stress; Urinary