title: Nonalbuminuric proteinuria as a biomarker for tubular damage in early development of nephropathy with type 2 diabetic patients.
abstract: OBJECTIVE
  The aim of this study was to evaluate the association between urinary nonalbumin protein (NAP) and urinary tubular markers in early diabetic nephropathy.
  
  
  METHODS
  Urinary NAP was measured in 118 patients with type 2 diabetes with estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m². Urine levels of tubular markers [kidney injury molecule (KIM)-1, neutrophil gelatinase-assoicated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP)] were measured by using an Enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups according to urinary NAP values.
  
  
  RESULTS
  The urine levels of KIM-1, NGAL and L-FABP were significantly higher in the third tertile group than in the first tertile group (all p < 0.001). There was a significant positive correlation between NAP and each tubular marker (KIM-1, NGAL and L-FABP) in univariate analysis (all p < 0.001). Urinary NAP was positively correlated with all urinary tubular markers after adjustment for age, duration of diabetes, systolic blood pressure, eGFR, low-density lipoprotein cholesterol, HbA1c and albumin-to-creatinine ratio (KIM-1 r = 0.170, p < 0.001; NGAL r = 0.142, p < 0.015 and L-FABP r = 0.262, p < 0.001). In normoalbuminuric patients (n = 58), urinary NAP was also significantly correlated with NGAL and L-FABP in multivariate regression analyses (r = 0.302, p = 0.030 and r = 0.430, p = 0.001).
  
  
  CONCLUSIONS
  These findings suggest that urinary NAP reflects tubular damage in the early-stage type 2 diabetic nephropathy (eGFR ≥ 60 mL/min/1.73 m²). We suggest that urinary NAP could be used as a biomarker for tubular damage in clinical practice.
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Song
authors.forename: In Joo
authors.initials: IJ
authors.lastname: Kim
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.forename: Ihm Soo
authors.initials: IS
authors.lastname: Kwak
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Yong Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000503:physiopathology / Q000652:urine; D042241:Early Diagnosis; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D006779:Hospitals, Public; D006785:Hospitals, University; D006801:Humans; D007684:Kidney Tubules / Q000503:physiopathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus; D056910:Republic of Korea; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus
keywords: diabetic nephropathy; kidney tubule; nonalbuminuric proteinuria; type 2 diabetes mellitus