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Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients

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Abstract

Chronic kidney disease (CKD) is a cause of coronary artery calcification (CAC) and an independent predictor of major adverse cardiac and cerebrovascular events (MACCE). Cathepsin K (CatK) is a lysosomal cysteine protease which affects vascular calcification and glucose metabolism disorder. We investigated the relationships among CatK, CAC, diabetes mellitus (DM) and MACCE in CKD patients. 113 consecutive CKD patients were enrolled. Their CAC was evaluated by computed tomography. Their plasma CatK level was measured by ELISA. They were divided into two groups by CatK levels and followed up for up to 3 years. The impact of CatK was analyzed in all participants, diabetic patients and non-diabetic patients. Kaplan–Meier analysis demonstrated a significant higher incidence of MACCE in the high CatK group (P = 0.028). The CatK level was significantly higher in patients with MACCE compared to that in patients without MACCE (P = 0.034). Cox’s model revealed the higher plasma CatK and BNP level as independent predictors of MACCE (P = 0.043 and P < 0.01, respectively). Only in non-diabetic patients, there was a significant correlation between CatK and CAC score, and high CatK group had a significant higher level of LDL-C and LDL-C/HDL-C ratio (P < 0.05 and P < 0.001, respectively) than low CatK group. And these lipid disorders were independent predictors of CatK elevation. In CKD patients, our results indicated an impact of higher CatK level on their MACCE. The significant association among the CatK level, CAC and MACCE was found in non-diabetic CKD patients.

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Abbreviations

CatK:

Cathepsin K

CAC:

Coronary artery calcification

CKD:

Chronic kidney disease

eGFR:

Estimated glomerular filtration rate

CAD:

Coronary artery disease

DM:

Diabetes mellitus

MACCE:

Major adverse cardiac and cerebrovascular events

BNP:

Brain natriuretic peptide

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Acknowledgments

The authors are indebted to all of the technicians, nurses and doctors in the CKD-specialized outpatients for their ongoing support.

Conflict of interest

None to declare.

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Authors and Affiliations

  1. Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Nagoya, Aichi, 466-8550, Japan

    Yusuke Izumi, Mutsuharu Hayashi, Ryota Morimoto, Xian Wu Cheng, Hongxian Wu, Hideki Ishii & Toyoaki Murohara

  2. Department of Cardiology, Fujita Health University Second Hospital, Nagoya, Japan

    Mutsuharu Hayashi, Daiji Yoshikawa & Hideo Izawa

  3. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshinari Yasuda & Seiichi Matsuo

  4. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yutaka Oiso

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  1. Yusuke Izumi
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Correspondence to Mutsuharu Hayashi.

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Izumi, Y., Hayashi, M., Morimoto, R. et al. Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients. Heart Vessels 31, 6–14 (2016). https://doi.org/10.1007/s00380-014-0570-z

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  • DOI: https://doi.org/10.1007/s00380-014-0570-z

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