title: Evaluation of method performance for oxidative stress biomarkers in urine and biological variations in urine of patients with type 2 diabetes mellitus and diabetic nephropathy.
abstract: BACKGROUND
  Oxidative stress biomarkers such as superoxide dismutase (CuZnSOD), catalase (CAT) and malondialdehyde (MDA) play an important role in the pathogenesis or progression of numerous diseases. Data regarding the biological variation and analytical quality specifications (imprecision, bias and total error) for judging the acceptability of method performance for oxidative stress biomarkers in urine are conspicuously lacking in the literature. Such data are important in setting analytical quality specifications, assessing the utility of population reference intervals (index of individuality) and assessing the significance of changes in serial results from an individual (reference change value; RCV).
  
  
  METHODS
  20 patients with type 2 diabetes mellitus (T2DM), 20 patients with diabetic nephropathy (DN) and 14 healthy individuals as control were involved in this study. Timed first morning urine samples were taken from patients and healthy groups on the zero, 1st, 3rd, 5th, 7th, 15th and 30th days. Index of individuality and reference change value were calculated from within-subject and between-subject variations. Methods of oxidative stress biomarkers in human blood were adopted in human urine and markers were measured as spectrophotometrically. Also, analytical quality specifications for evaluation of the method performance were established for oxidative stress biomarkers in urine.
  
  
  RESULTS
  Within-subject variations of oxidative stress biomarkers were significantly higher in patients with DN and T2DM compared to healthy subjects. MDA showed low individuality, and within-subject variances of MDA were larger than between-subject variances in all groups. However, CAT and CuZnSOD showed strong individuality, but within-subject variances of them were smaller than between-subject variances in all groups. RCVs of all analytes in diabetic patients were relatively higher, because of high within-subject variation, resulting in a higher RCV. Also, the described methodology achieves these goals, with analytical CVs of < 3.5% for all analytes. Goals for bias and total error were 6.0-7.9% and 12.5-23.3%, respectively.
  
  
  CONCLUSIONS
  RCVs concept for predicting the clinical status in diabetic patients represents an optimization of laboratory reporting and could be a valuable tool for clinical decision. Furthermore, for oxidative stress biomarkers' measurements in urine, the desirable imprecision goals based on biological variation are obtainable by current methodologies.
authors: Department of Biochemistry, Sutcu Imam University Faculty of Medicine, Avsar Campus, 46050 Kahramanmaras, Turkey.
authors: Ergul Belge
authors: EB
authors: Kurutas
authors: Department of Anatomy, Fatih University Faculty of Medicine, Büyükçekmece Campus, 34500 Istanbul, Turkey.
authors: Yakup
authors: Y
authors: Gumusalan
authors: Department of Gastroenterology, Sutcu Imam University Faculty of Medicine, Kahramanmaras, Turkey.
authors: Ali
authors: A
authors: Cetinkaya
authors: Department of Nephrology, Selahaddin Eyyubi University Faculty of Medicine, Bağlar Campus, 21090 Diyarbakir, Turkey.
authors: Ekrem
authors: E
authors: Dogan
keywords: Biological variation; DN; Oxidative stress biomarkers; Reference change value; T2DM
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