title: Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.
abstract: BACKGROUND
  Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).
  
  
  METHODS
  Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.
  
  
  METHODS
  3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008.
  
  
  METHODS
  Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration.
  
  
  RESULTS
  Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.
  
  
  METHODS
  Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories).
  
  
  RESULTS
  There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths.
  
  
  CONCLUSIONS
  Urine NGAL was measured only once.
  
  
  CONCLUSIONS
  Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.affiliation: Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Anderson
authors.affiliation: Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.affiliation: Department of Medicine, Jesse Brown VAMC and University of Illinois Hospital and Health Sciences System, Chicago, IL.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fischer
authors.affiliation: Department of Epidemiology, Tulane University, New Orleans, LA.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Radhakrishna R
authors.initials: RR
authors.lastname: Kallem
authors.affiliation: The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Master
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Miller
authors.affiliation: Department of Medicine, Joslin Diabetes Center & Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Rosas
authors.affiliation: St. Claire Specialty Physicians, St. John Hospital & Medical Center, Detroit, MI.
authors.forename: Susan
authors.initials: S
authors.lastname: Steigerwalt
authors.affiliation: Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA; Division of Research, Kaiser Permanente Northern California, Oakland, CA. Electronic address: hsuchi@medicine.ucsf.edu.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality* / Q000652:urine*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000401:mortality* / Q000652:urine*; D012307:Risk Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
keywords: Chronic Renal Insufficiency Cohort (CRIC) Study; Neutrophil gelatinase-associated lipocalin (NGAL); biomarker; cardiovascular disease; chronic kidney disease (CKD); ischemic atherosclerotic event; renal tubular dysfunction; renal tubular injury