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Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.
Am J Kidney Dis. 2015 Feb; 65(2):267-74.AJ

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).

STUDY DESIGN

Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.

SETTING & PARTICIPANTS

3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008.

PREDICTOR

Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration.

OUTCOMES

Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.

MEASUREMENTS

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.

LIMITATIONS

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+Show Affiliations

Department of Medicine, University of California, San Francisco, San Francisco, CA.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.Division of Research, Kaiser Permanente Northern California, Oakland, CA.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.Department of Medicine, Jesse Brown VAMC and University of Illinois Hospital and Health Sciences System, Chicago, IL.Department of Epidemiology, Tulane University, New Orleans, LA.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.Department of Medicine, Johns Hopkins University, Baltimore, MD.Department of Medicine, Joslin Diabetes Center & Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.St. Claire Specialty Physicians, St. John Hospital & Medical Center, Detroit, MI.Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.Department of Medicine, University of Maryland, Baltimore, MD.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.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25311702

Citation

Liu, Kathleen D., et al. "Urine Neutrophil Gelatinase-associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 65, no. 2, 2015, pp. 267-74.
Liu KD, Yang W, Go AS, et al. Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;65(2):267-74.
Liu, K. D., Yang, W., Go, A. S., Anderson, A. H., Feldman, H. I., Fischer, M. J., He, J., Kallem, R. R., Kusek, J. W., Master, S. R., Miller, E. R., Rosas, S. E., Steigerwalt, S., Tao, K., Weir, M. R., & Hsu, C. Y. (2015). Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 65(2), 267-74. https://doi.org/10.1053/j.ajkd.2014.07.025
Liu KD, et al. Urine Neutrophil Gelatinase-associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;65(2):267-74. PubMed PMID: 25311702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urine neutrophil gelatinase-associated lipocalin and risk of cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. AU - Liu,Kathleen D, AU - Yang,Wei, AU - Go,Alan S, AU - Anderson,Amanda H, AU - Feldman,Harold I, AU - Fischer,Michael J, AU - He,Jiang, AU - Kallem,Radhakrishna R, AU - Kusek,John W, AU - Master,Stephen R, AU - Miller,Edgar R,3rd AU - Rosas,Sylvia E, AU - Steigerwalt,Susan, AU - Tao,Kaixiang, AU - Weir,Matthew R, AU - Hsu,Chi-Yuan, AU - ,, Y1 - 2014/10/11/ PY - 2014/02/08/received PY - 2014/07/28/accepted PY - 2014/10/15/entrez PY - 2014/10/15/pubmed PY - 2015/3/21/medline KW - Chronic Renal Insufficiency Cohort (CRIC) Study KW - Neutrophil gelatinase-associated lipocalin (NGAL) KW - biomarker KW - cardiovascular disease KW - chronic kidney disease (CKD) KW - ischemic atherosclerotic event KW - renal tubular dysfunction KW - renal tubular injury SP - 267 EP - 74 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 65 IS - 2 N2 - 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). STUDY DESIGN: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. SETTING & PARTICIPANTS: 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. PREDICTOR: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. OUTCOMES: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. MEASUREMENTS: 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. LIMITATIONS: 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/25311702/Urine_neutrophil_gelatinase_associated_lipocalin_and_risk_of_cardiovascular_disease_and_death_in_CKD:_results_from_the_Chronic_Renal_Insufficiency_Cohort__CRIC__Study_ DB - PRIME DP - Unbound Medicine ER -