4.6 Article

Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men

Journal

ATHEROSCLEROSIS
Volume 227, Issue 2, Pages 408-413

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2013.01.009

Keywords

Chronic kidney disease; Epidemiology; Inflammation; Mortality; NGAL; Risk factors

Funding

  1. Uppsala-Orebro Regional Research Council (RFR)
  2. Swedish Research Council [2006-6555, 2012-1727, 2012-2215]
  3. Swedish Heart-Lung foundation
  4. Thureus foundation
  5. Marianne and Marcus Wallenberg Foundation
  6. Dalarna University
  7. Uppsala University

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Objective: Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known. Methods: This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes. Results: U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFR(CysC)) but not urinary Albumin (u-Alb). A combination of low eGFR(CysC) (<= 60 mL/min), high u-Alb (>= 3 mg/mmol Cr) and high u-NGAL (>= 1.19 mu g/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs. 1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFR(CysC) or u-Alb. Conclusion: This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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