title: Clinical value of inflammatory urinary biomarkers in overt diabetic nephropathy: a prospective study.
abstract: OBJECTIVE
  The evolution of diabetic nephropathy is incompletely accounted by current clinical tools. New biomarkers may refine patient assessment and help monitor therapy. We compared the added predictive value of 7 candidate inflammatory urinary biomarkers to known risk factors of progression.
  
  
  METHODS
  We prospectively followed 83 patients with overt diabetic nephropathy for a median 2.1 years and obtained repeated measurements of proteinuria, IL-1β, IL-6, IL-8, MCP-1, TNF-α, TGF-β1, and PAI-1.
  
  
  RESULTS
  Patients had an initial estimated glomerular filtration rate of 25 ± 9 mL/min/1.73 m(2), blood pressure of 142/69 mmHg and used a median of 4 anti-hypertensive medications over the course of the study. The observed rate of renal function decline was 2.9 ± 3.0 mL/min/1.73 m(2)/year. All urinary biomarkers levels were collinear and for each one except IL-1β, elevated levels predicted a more rapid progression. MCP-1 was the only biomarker increasing during follow-up, which also correlated with a worst outcome. Using multivariate linear regression adjusting for clinical risk factors of progression, urinary MCP-1 and TGF-β1 predicted progression independently and additively to the degree of proteinuria. We dichotomized these 3 biomarkers and observed a renal function decline with 0, 1, 2 or 3 elevated biomarkers of -0.8 ± 1.4, -2.1 ± 2.1, -4.2 ± 2.8 and -6.0 ± 2.8 mL/min/1.73 m(2)/year, respectively (p<0.001).
  
  
  CONCLUSIONS
  Multiple urinary biomarkers predict outcome in overt diabetic nephropathy. However, urinary MCP-1 and TGF-β1 are also independent and additive to proteinuria in predicting the rate of renal function decline and could serve as useful clinical tools in patient risk stratification.
authors.affiliation: Nephrology Division, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada.
authors.forename: Jacobien C
authors.initials: JC
authors.lastname: Verhave
authors.forename: Josée
authors.initials: J
authors.lastname: Bouchard
authors.forename: Rémi
authors.initials: R
authors.lastname: Goupil
authors.forename: Vincent
authors.initials: V
authors.lastname: Pichette
authors.forename: Soumeya
authors.initials: S
authors.lastname: Brachemi
authors.forename: François
authors.initials: F
authors.lastname: Madore
authors.forename: Stéphan
authors.initials: S
authors.lastname: Troyanov
mesh_terms: D015415:Biomarkers / Q000652:urine; D018932:Chemokine CCL2 / Q000652:urine; D003928:Diabetic Nephropathies / Q000652:urine*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000652:urine; D015850:Interleukin-6 / Q000652:urine; D016209:Interleukin-8 / Q000652:urine; D017395:Plasminogen Activator Inhibitor 1 / Q000652:urine; D011446:Prospective Studies; D053773:Transforming Growth Factor beta1 / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000652:urine
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha
keywords: Diabetic nephropathy; MCP-1; Proteinuria; Rate of renal function decline; TGF-β1; Urinary biomarkers