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Urinary neutrophil gelatinase-associated lipocalin as a predictor of cardiovascular events in patients with chronic kidney disease

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Abstract

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) events. Recently, elevated neutrophil gelatinase-associated lipocalin (NGAL) levels have been reported in patients with heart failure, coronary heart disease, or stroke. Our aim was to assess urinary NGAL as a predictor of CV events in patients with CKD. This was a prospective observational cohort study of 404 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, hospitalization for worsening heart failure, stroke and dissection of aorta. During a mean follow-up period of 33 months, 77 CV events (19.1 %) occurred. After adjustment for gender, age, diabetes, previous cardiovascular disease, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate, hemoglobin, and high-sensitivity C-reactive protein, patients with the other quartiles of urinary NGAL had significantly higher risk of CV events compared with patients with the lowest quartile (hazard ratio (HR) 2.81, 95 % confidence interval (CI) 1.01–7.81, P = 0.047 for Q2, HR 3.31, 95 % CI 1.22–9.00, P = 0.019 for Q3, and HR 3.27, 95 % CI 1.15–9.29, P = 0.026 for Q4). Regarding the combination of urinary NGAL with UACR, we also stratified patients into four groups according to whether the level of each marker was above or below the median (61.8 μg per gram creatinine (gCr) for NGAL and 351.1 mg/gCr for UACR). Four-year CV event-free survival rates were 89.2, 79.6, 71.8, and 51.5 % in order for the four respective groups (P < 0.0001). Elevated urinary NGAL was able to predict future CV events in CKD patients, and had incremental predictive value with elevated UACR.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Diabetic Nephropathy and Nephrosclerosis Research, and a Grant-in-Aid for Progressive Renal Diseases Research, Research on Intractable Disease, from the Ministry of Health, Labor and Welfare of Japan and by JSPS KAKENHI Grant Number 24590712.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutukaek-cho, Toyoake, Aichi, 470-1192, Japan

    Midori Hasegawa, Kazuo Takahashi, Hiroki Hayashi, Shigehisa Koide, Makoto Tomita & Yukio Yuzawa

  2. Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan

    Junichi Ishii

  3. Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan

    Yukio Ozaki

  4. Laboratory of Clinical Medicine, Fujita Health University, Toyoake, Japan

    Fumihiko Kitagawa

  5. Division of Medical Statistics, Fujita Health University, Toyoake, Japan

    Hiroshi Takahashi

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  1. Midori Hasegawa
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  2. Junichi Ishii
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  3. Fumihiko Kitagawa
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Correspondence to Midori Hasegawa.

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Hasegawa, M., Ishii, J., Kitagawa, F. et al. Urinary neutrophil gelatinase-associated lipocalin as a predictor of cardiovascular events in patients with chronic kidney disease. Heart Vessels 30, 81–88 (2015). https://doi.org/10.1007/s00380-013-0454-7

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  • DOI: https://doi.org/10.1007/s00380-013-0454-7

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