title: Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy.
abstract: Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary albumin excretion 1141 mg/24 h. Patients with the highest compared with the lowest quartile of urinary NGAL at baseline had higher urinary KIM-1 levels and a significant decrease in their GFR each year. Using linear regression analysis, we found that elevated urinary NGAL and KIM-1 concentrations were associated with a faster decline in GFR, but not after adjustment for known promoters of progression. Urinary LFABP was not related to decline in GFR. Losartan treatment (100 mg/day) reduced urinary KIM-1 by 43% over a 12-month period. Thus, urine biomarker measurements in patients with type 1 diabetic nephropathy did not provide additional prognostic information to that of known progression promoters.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. Sene@steno.dk
authors.forename: Stine E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: Steen
authors.initials: S
authors.lastname: Andersen
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zdunek
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
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 / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus
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; D019808:Losartan