title: Inflammation and coagulation markers and kidney function decline: the Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: BACKGROUND
  The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFR(cys)) >60 mL/min/1.73 m(2) and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry.
  
  
  METHODS
  We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d-dimer levels with kidney function decrease.
  
  
  METHODS
  Kidney function decrease was assessed primarily by repeated measurements of eGFR(cys) over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m(2) per year. Incident low eGFR was defined as the onset of eGFR(cys) <60 mL/min/1.73 m(2) at any follow-up examination and eGFR(cys) decrease ≥1 mL/min/1.73 m(2) per year.
  
  
  RESULTS
  Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFR(cys) was 96 mL/min/1.73 m(2) and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (β = -0.25; 95% CI, -0.38 to -0.12; P < 0.001), followed by IL-6 (β = -0.16; 95% CI, -0.29 to -0.03; P = 0.01), CRP (β = -0.09; 95% CI, -0.22 to 0.03; P = 0.1), and fibrinogen levels (β = -0.09; 95% CI, -0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19).
  
  
  CONCLUSIONS
  Observational study design and absence of measured GFR.
  
  
  CONCLUSIONS
  Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.
authors.affiliation: Department of Surgery, University of California, San Francisco, CA 94143, USA. jade.hiramoto@ucsfmedctr.org
authors.forename: Jade S
authors.initials: JS
authors.lastname: Hiramoto
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Linda
authors.initials: L
authors.lastname: Fried
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.forename: Walter
authors.initials: W
authors.lastname: Palmas
authors.forename: Mark
authors.initials: M
authors.lastname: Sarnak
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000208:ethnology / Q000503:physiopathology*; D001777:Blood Coagulation / Q000502:physiology*; D002097:C-Reactive Protein / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
chemical_list: D015850:Interleukin-6; D005169:Factor VIII; D005340:Fibrinogen; D002097:C-Reactive Protein