title: The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP.
abstract: OBJECTIVE
  Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP).
  
  
  METHODS
  A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria. After 2 months washout of all antihypertensive medication except bendroflumethiazid, patients were treated in random order with irbesartan 300, 600 and 900 mg for 2 months.
  
  
  METHODS
  Urinary tubular markers at baseline and after each treatment period (ELISA), 24-h blood pressure, glomerular filtration rate (GFR, (51)CrEDTA) and 24-h urine albumin excretion (UAER).
  
  
  RESULTS
  Fifty-two patients completed the study (41 male). Age (mean (SD)): 58(10) years and diabetes duration 13(8) years. Baseline GFR was 101(24) and UAER (geometric mean [95%CI]) 133 (103-172) mg/24 h. With increasing doses of irbesartan (300, 600, 900 mg) u-KIM1 was reduced with 15%, 10% and 15% (p = 0.07 between 300 mg vs. baseline and no difference between doses). Patients with high u-KIM1 at baseline (above median) had a 32% reduction in u-KIM1 during treatment (p = 0.01). No significant decline in U-NGAL compared to baseline. U-LFABP increased during treatment (p < 0.01).
  
  
  CONCLUSIONS
  Irbesartan treatment reduced levels of the tubular marker u-KIM1 in patients with type 2 diabetes and microalbuminuria. u-NGAL changed insignificantly and u-LFABP increased. More studies with longer follow up are needed to determine the role of tubular markers in monitoring treatment effect and prediction of prognosis in diabetic nephropathy.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. Sene@steno.dk
authors.forename: Stine E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: Kasper
authors.initials: K
authors.lastname: Rossing
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zdunek
authors.forename: Berit R
authors.initials: BR
authors.lastname: Jensen
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000368:Aged; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000209:Acute-Phase Proteins; 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