title: Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus.
abstract: BACKGROUND
  Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study.
  
  
  METHODS
  Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/√2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included.
  
  
  RESULTS
  Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 µg/min and mean iohexol GFR 129 mL/min/1.73 m(2). No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = -0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex.
  
  
  CONCLUSIONS
  Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN.
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
authors: Gudeta D
authors: GD
authors: Fufaa
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
authors: E Jennifer
authors: EJ
authors: Weil
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
authors: Robert G
authors: RG
authors: Nelson
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
authors: Robert L
authors: RL
authors: Hanson
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
authors: William C
authors: WC
authors: Knowler
authors: Ohio State University, Columbus, OH, USA.
authors: Brad H
authors: BH
authors: Rovin
authors: Ohio State University, Columbus, OH, USA.
authors: Haifeng
authors: H
authors: Wu
authors: University of Louisville, Louisville, KY, USA.
authors: Jon B
authors: JB
authors: Klein
authors: University of Pennsylvania, Philadelphia, PA, USA.
authors: Theodore E
authors: TE
authors: Mifflin
authors: University of Pennsylvania, Philadelphia, PA, USA.
authors: Harold I
authors: HI
authors: Feldman
authors: Boston University, Boston, MA, USA.
authors: Ramachandran S
authors: RS
authors: Vasan
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
authors: Paul L
authors: PL
authors: Kimmel
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
authors: John W
authors: JW
authors: Kusek
authors: Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN 55454, USA.
authors: Michael
authors: M
authors: Mauer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine*; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D064451:Hepcidins / Q000652:urine*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System; D055815:Young Adult
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D064451:Hepcidins
keywords: biomarkers; diabetic nephropathy; hepcidin; interstitial fibrosis; monocyte chemoattractant protein-1
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