title: Glomerular and tubular damage markers are elevated in patients with diabetes.
abstract: OBJECTIVE
  We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and cystatin C), and distal tubular (heart fatty acid-binding protein [H-FABP]) damage markers with kidney disease severity, as assessed by albuminuria and estimated glomerular filtration rate (eGFR).
  
  
  METHODS
  Damage markers were measured in triplicate in fresh morning urine samples and in plasma.
  
  
  RESULTS
  Of the diabetic patients, 41 were normoalbuminuric, 41 were microalbuminuric, and 12 were macroalbuminuric. Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. Urinary concentrations of all markers increased per albuminuria stratum, except KIM-1. All urinary damage markers, except KIM-1, were significantly associated with albuminuria, independent of age, sex, and plasma concentrations of the corresponding biomarker (standard βs between 0.35 and 0.87; all P ≤ 0.001). All urinary damage markers, except KIM-1, were significantly associated with the eGFR in univariate models (standard βs between -0.38 and -0.21; all P < 0.04). After adjusting for age, sex, plasma concentration of the corresponding damage marker, and albuminuria, only the association of H-FABP with eGFR remained significant (standard β -0.26; P = 0.037).
  
  
  CONCLUSIONS
  Glomerular and tubular markers are associated with albuminuria, independently of eGFR, suggesting that albuminuria reflects both glomerular and tubulointerstitial damage. Only urinary H-FABP is associated with eGFR independently of albuminuria and, therefore, may be a promising urinary damage marker to assess diabetic kidney disease.
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen,Groningen, the Netherlands. r.t.gansevoort@int.umcg.nl
authors.forename: Ferdau L
authors.initials: FL
authors.lastname: Nauta
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Boertien
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.forename: Paul E
authors.initials: PE
authors.lastname: de Jong
authors.forename: Henk
authors.initials: H
authors.lastname: Bilo
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000118:Acetylglucosaminidase / Q000097:blood / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000652:urine*; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000652:urine; D008875:Middle Aged; D015999:Multivariate Analysis; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000652:urine; D011991:Receptors, Virus / Q000097:blood
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; 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; D000118:Acetylglucosaminidase