title: Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes.
abstract: OBJECTIVE
  Renal dysfunction has been reported in normoalbuminuric patients, demonstrating the necessity to improve the diagnostic and prognostic tools for diabetic kidney disease (DKD) investigation. Therefore, the aim of this study was to investigate whether the urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are increased in type 2 diabetes mellitus (DM) patients with normal or mildly increased albuminuria.
  
  
  METHODS
  In this study, 117 type 2 DM patients classified into three groups according to urinary albumin/creatinine ratio (uACR): uACR<10mg/g creatinine, uACR 10-30mg/g creatinine and uACR>30mg/g creatinine were enrolled. Urinary concentrations of KIM-1 (uKIM-1) and NGAL (uNGAL) were measured.
  
  
  RESULTS
  uKIM-1 levels increased progressively from uACR<10mg/g creatinine (69.0±20.8pg/ml) to uACR 10-30mg/g creatinine (106.1±41.2pg/ml) and to uACR>30mg/g creatinine (166.0±31.9pg/ml) (P<0.001). In addition, uNGAL levels increased progressively from uACR<10mg/g creatinine (29.5±8.8ng/ml) to uACR 10-30mg/g creatinine (51.7±10.9ng/ml) and to uACR>30mg/g creatinine (71.0±9.6ng/ml) (P<0.001) patients. Similarly, both uKIM-1 and uNGAL adjusted by urinary creatinine were increased in patients with uACR 10-30mg/g creatinine. Significant and positive correlations were observed between uACR, uKIM-1 and uNGAL.
  
  
  CONCLUSIONS
  uKIM-1 and uNGAL were increased in type 2 DM patients with normal or mildly increased albuminuria, which indicates that tubular and glomerular injuries may be occurring even at the earliest stage of DKD.
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; University Hospital, Santa Maria, RS, Brazil; Pharmaceutical Sciences Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: José Antonio M
authors.initials: JA
authors.lastname: de Carvalho
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Pharmaceutical Sciences Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Etiane
authors.initials: E
authors.lastname: Tatsch
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Pharmaceutical Sciences Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Bruna S
authors.initials: BS
authors.lastname: Hausen
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Yãnaí S
authors.initials: YS
authors.lastname: Bollick
authors.affiliation: Pharmaceutical Sciences Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Pharmacology Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Moretto
authors.affiliation: Pharmacology Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Duarte
authors.affiliation: Pharmacology Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Department of Health Sciences, Universidade Luterana do Brasil, Santa Maria, RS, Brazil.
authors.forename: Marta M M F
authors.initials: MM
authors.lastname: Duarte
authors.affiliation: University Hospital, Santa Maria, RS, Brazil.
authors.forename: Sílvia W K
authors.initials: SW
authors.lastname: Londero
authors.affiliation: Pharmacology Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Department of Clinical Medicine, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Melissa O
authors.initials: MO
authors.lastname: Premaor
authors.affiliation: Pharmacology Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Department of Clinical Medicine, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Fabio V
authors.initials: FV
authors.lastname: Comim
authors.affiliation: Department of Clinical Chemistry, Ghent University Hospital, Gent, Belgium.
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Pharmaceutical Sciences Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Pharmacology Postgraduate Program, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. Electronic address: rnmoresco@ufsm.br.
authors.forename: Rafael N
authors.initials: RN
authors.lastname: Moresco
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology* / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism*; D006801:Humans; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D003404:Creatinine
keywords: Diabetic kidney disease; Kidney injury molecule-1; Neutrophil gelatinase-associated lipocalin; Tubular damage