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Cathepsin-K is a potential cardiovascular risk biomarker in prevalent hemodialysis patients

  • Nephrology - Original Paper
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Abstract

Purpose

Cardiovascular (CV) disease remains the leading cause of mortality among end-stage kidney disease (ESKD) patients. Cathepsin-K (CatK), a small cysteine protease involved in bone and extracellular matrix remodeling, has recently emerged as a key-factor in the pathogenesis of various conditions predisposing to CV disease, including atherosclerosis, obesity, diabetes, and vascular calcification. In this pilot prospective study, we aimed at evaluating the clinical significance and the predictive power of CatK in a small cohort of hemodialysis (HD) patients.

Methods

Cathepsin-K was measured in 54 prevalent HD patients and in 30 controls together with routine parameters. Patients were then followed up to 26 months and the time of cardiovascular death (endpoint of the study prospective phase) recorded.

Results

CatK levels were increased in the HD cohort as compared with controls (p < 0.001). In HD patients, CatK was also independently correlated to PTH (β = 0.368; p = 0.001), alkaline phosphatase (β = 0.383; p < 0.001), C-reactive protein (β = 0.260; p = 0.01), and white cell count (β = − 0.219; p = 0.02). After baseline assessment, patients were followed for CV death (mean follow-up 24.8 ± 3.1 months). Kaplan–Meier analysis showed a worsen survival (log-rank p = 0.04) in HD patients with CatK levels > 440 pg/mL (best ROC-derived cut-off with 69.6% sensitivity and 79.8% specificity) with a crude HR (Mantel–Haenszel) of CV death of 3.46 (95% CI 1.89–13.44).

Conclusions

In prevalent HD patients, altered CatK levels may reflect mineral dysmetabolism and inflammation, and predict CV death in the mid-term. These preliminary findings prompt the rationale for further investigations on larger cohorts to validate CatK as a biomarker for improving CV risk stratification in ESKD.

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References

  1. National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases B, MD (2017) United States Renal Data System. 2017 USRDS annual data report: epidemiology of kidney disease in the United States. https://www.usrds.org/2017/view/v2_05.aspx. Accessed 24 Apr 2020

  2. Cozzolino M, Galassi A, Pivari F, Ciceri P, Conte F (2017) The cardiovascular burden in end-stage renal disease. Contrib Nephrol 191:44–57. https://doi.org/10.1159/000479250

    Article  PubMed  Google Scholar 

  3. Vidak E, Javorsek U, Vizovisek M, Turk B (2019) Cysteine cathepsins and their extracellular roles: shaping the microenvironment. Cells. https://doi.org/10.3390/cells8030264

    Article  PubMed  PubMed Central  Google Scholar 

  4. Troen BR (2004) The role of cathepsin K in normal bone resorption. Drug News Perspect 17(1):19–28. https://doi.org/10.1358/dnp.2004.17.1.829022

    Article  CAS  PubMed  Google Scholar 

  5. Liu CL, Guo J, Zhang X, Sukhova GK, Libby P, Shi GP (2018) Cysteine protease cathepsins in cardiovascular disease: from basic research to clinical trials. Nat Rev Cardiol 15(6):351–370. https://doi.org/10.1038/s41569-018-0002-3

    Article  CAS  PubMed  Google Scholar 

  6. Cheng XW, Kikuchi R, Ishii H, Yoshikawa D, Hu L, Takahashi R, Shibata R, Ikeda N, Kuzuya M, Okumura K, Murohara T (2013) Circulating cathepsin K as a potential novel biomarker of coronary artery disease. Atherosclerosis 228(1):211–216. https://doi.org/10.1016/j.atherosclerosis.2013.01.004

    Article  CAS  PubMed  Google Scholar 

  7. Izumi Y, Hayashi M, Morimoto R, Cheng XW, Wu H, Ishii H, Yasuda Y, Yoshikawa D, Izawa H, Matsuo S, Oiso Y, Murohara T (2016) Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients. Heart Vessels 31(1):6–14. https://doi.org/10.1007/s00380-014-0570-z

    Article  PubMed  Google Scholar 

  8. Mazzaferro S, De Martini N, Rotondi S, Tartaglione L, Urena-Torres P, Bover J, Pasquali M, CKD-MBD E-EWGo (2020) Bone, inflammation and chronic kidney disease. Clinica Chimica Acta Int J Clin Chem 506:236–240. https://doi.org/10.1016/j.cca.2020.03.040

    Article  CAS  Google Scholar 

  9. Chapurlat RD, Confavreux CB (2016) Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology 55(10):1714–1725. https://doi.org/10.1093/rheumatology/kev410

    Article  PubMed  Google Scholar 

  10. Suda N, Baba O, Udagawa N, Terashima T, Kitahara Y, Takano Y, Kuroda T, Senior PV, Beck F, Hammond VE (2001) Parathyroid hormone-related protein is required for normal intramembranous bone development. J Bone Miner Res 16(12):2182–2191. https://doi.org/10.1359/jbmr.2001.16.12.2182

    Article  CAS  PubMed  Google Scholar 

  11. Carrillo-Lopez N, Panizo S, Alonso-Montes C, Roman-Garcia P, Rodriguez I, Martinez-Salgado C, Dusso AS, Naves M, Cannata-Andia JB (2016) Direct inhibition of osteoblastic Wnt pathway by fibroblast growth factor 23 contributes to bone loss in chronic kidney disease. Kidney Int 90(1):77–89. https://doi.org/10.1016/j.kint.2016.01.024

    Article  CAS  PubMed  Google Scholar 

  12. Podgorski I, Linebaugh BE, Koblinski JE, Rudy DL, Herroon MK, Olive MB, Sloane BF (2009) Bone marrow-derived cathepsin K cleaves SPARC in bone metastasis. Am J Pathol 175(3):1255–1269. https://doi.org/10.2353/ajpath.2009.080906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hao L, Zhu G, Lu Y, Wang M, Jules J, Zhou X, Chen W (2015) Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role. FEBS Lett 589(12):1331–1339. https://doi.org/10.1016/j.febslet.2015.04.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kramer L, Turk D, Turk B (2017) The future of cysteine cathepsins in disease management. Trends Pharmacol Sci 38(10):873–898. https://doi.org/10.1016/j.tips.2017.06.003

    Article  CAS  PubMed  Google Scholar 

  15. Cheng XW, Shi GP, Kuzuya M, Sasaki T, Okumura K, Murohara T (2012) Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication. Circulation 125(12):1551–1562. https://doi.org/10.1161/CIRCULATIONAHA.111.066712

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Renal Unit, “Magna Graecia” University, Campus Salvatore Venuta, Viale Europa, Catanzaro, 88100, Italy

    Davide Bolignano, Valentina Arcidiacono, Caterina Vita, Michele Provenzano, Giorgio Fuiano, Michele Andreucci & Giuseppe Coppolino

  2. Division of Clinical Pathology, “Magna Graecia” University, Catanzaro, Italy

    Marta Greco, Omar Tripolino & Daniela Patrizia Foti

  3. Renal Unit, “Pugliese-Ciaccio” Hospital of Catanzaro, Catanzaro, Italy

    Cinzia Donato & Salvatore Chiarella

  4. Pharmacology Unit, “Magna Graecia” University, Catanzaro, Italy

    Giovambattista De Sarro & Emilio Russo

Authors
  1. Davide Bolignano
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  2. Marta Greco
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  3. Valentina Arcidiacono
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  4. Omar Tripolino
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  14. Giuseppe Coppolino
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Correspondence to Davide Bolignano.

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Bolignano, D., Greco, M., Arcidiacono, V. et al. Cathepsin-K is a potential cardiovascular risk biomarker in prevalent hemodialysis patients. Int Urol Nephrol 53, 171–175 (2021). https://doi.org/10.1007/s11255-020-02602-y

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  • DOI: https://doi.org/10.1007/s11255-020-02602-y

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