title: Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril.
abstract: OBJECTIVE
  Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment on urinary NGAL was evaluated in diabetic nephropathy.
  
  
  METHODS
  This was a cross-sectional study in 58 normoalbuminuric (u-albumin <30 mg/24 h), 45 microalbuminuric (30-300 mg/24 h) and 45 macroalbuminuric (>300 mg/24 h) Type 1 diabetic patients and 55 non-diabetic control subjects. Furthermore, in a second study, urine-NGAL was measured in a randomized cross-over study of 56 Type 1 diabetic patients with diabetic nephropathy treated with lisinopril 20, 40 and 60 mg daily.
  
  
  RESULTS
  Urine-NGAL levels were [geometric mean (95% CI)]: control subjects 74 (52-104) (pg/mmol creatinine), normoalbuminuric 146 (97-221), microalbuminuric 222 (158-312) and macroalbuminuric group 261 (175-390). Urine-NGAL increased significantly from the normo- to the micro- and further to the macroalbuminuric group (P<0.05). Urine-NGAL was higher in normoalbuminuric vs. control subjects (P<0.01). Plasma-NGAL was significantly higher in the normoalbuminuric and macroalbuminuric groups than in the control group. Urine-KIM1 was higher in all diabetic groups than in the control group (P<0.001), with no difference between diabetic groups. During lisinopril treatment, urine-NGAL was reduced (95% CI) 17% (11-50) (not significant).
  
  
  CONCLUSIONS
  Urine-NGAL and urine-KIM1 (u-KIM1) are elevated in Type1 diabetic patients, with or without albuminuria, indicating tubular damage at an early stage. Urine-NGAL increases significantly with increasing albuminuria. The ACE inhibitor lisinopril reduced urine-NGAL, but this was not statistically significant.
authors.affiliation: Steno Diabetes Center, Gentofte Hospital, Denmark. Sene@steno.dk
authors.forename: S E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: K J
authors.initials: KJ
authors.lastname: Schjoedt
authors.forename: A S
authors.initials: AS
authors.lastname: Astrup
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: M
authors.initials: M
authors.lastname: Lajer
authors.forename: P R
authors.initials: PR
authors.lastname: Hansen
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
authors.forename: P
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000419:Albuminuria / Q000652:urine*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000652:urine*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000652:urine*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000652:urine*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus / Q000187:drug effects
chemical_list: D000209:Acute-Phase 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; D017706:Lisinopril