Current issue
Archive
Manuscripts accepted
About the Journal
Editorial office
Editorial board
Section Editors
Abstracting and indexing
Subscription
Contact
Ethical standards and procedures
Most read articles
Instructions for authors
Article Processing Charge (APC)
Regulations of paying article processing charge (APC)
HEART FAILURE / CLINICAL RESEARCH
sαKlotho protein is a useful biomarker and a promising cardioprotective agent in acute heart failure
1
Department of Cardiology, University Hospital, Institute of Medical Sciences, University of Opole, Poland
2
Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry and Laboratory Haematology, Faculty of Pharmacy, Wrocław Medical University, Poland
3
Department of Clinical Biochemistry and Laboratory Diagnostics, Institute of Medical Sciences, University of Opole, Poland
4
University Hospital of Opole, Poland
Submission date: 2024-04-25
Final revision date: 2024-07-31
Acceptance date: 2024-08-12
Online publication date: 2024-09-07
Corresponding author
Joanna Płonka
Department of Cardiology University Hospital Institute of Medical Sciences University of Opole Opole, Poland
Department of Cardiology University Hospital Institute of Medical Sciences University of Opole Opole, Poland
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Acute heart failure (AHF) is a heterogeneous and etiologically complex syndrome with a poor prognosis. sαKlotho (sαKl) is an antiaging protein with pleiotropic actions. The aim of this study was to assess the level and kinetics of sαKl during an episode of AHF and its long-term prognostic utility in a population of AHF patients.
Material and methods:
It was a prospective multicenter study, which enrolled 133 participants. 112 consecutive patients were admitted to the intensive cardiac care unit with a diagnosis of AHF (age 68 [IQR: 60–75] years, ejection fraction 30% [IQR: 20–38], new-onset AHF 46% of the population). Twenty-one individuals formed the control group. sαKl, N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined in serum at admission and at discharge. The main clinical outcomes assessed in the study were 3-year all-cause mortality or HF rehospitalization.
Results:
sKl concentration significantly increased during episodes of AHF. A weak negative correlation was observed between sαKl and NT-proBNP at admission and discharge. Only patients with ischemic etiology of AHF did not have considerably elevated sαKl values at admission. Women and men had similar biomarker values. Smoking did not affect sαKl in our study. Patients who developed the combined endpoint during 3-year follow-up showed a smaller increase in sαKl values on admission compared to the control group (p = 0.169) and weaker biomarker kinetics during hospitalization as compared with the group free of adverse outcomes (p = 0.01).
Conclusions:
sαKl level is upregulated during an acute episode of HF and may serve as a useful biomarker. A weak reduction in sαKl levels during treatment may serve as an indicator of poor long-term prognosis.
Acute heart failure (AHF) is a heterogeneous and etiologically complex syndrome with a poor prognosis. sαKlotho (sαKl) is an antiaging protein with pleiotropic actions. The aim of this study was to assess the level and kinetics of sαKl during an episode of AHF and its long-term prognostic utility in a population of AHF patients.
Material and methods:
It was a prospective multicenter study, which enrolled 133 participants. 112 consecutive patients were admitted to the intensive cardiac care unit with a diagnosis of AHF (age 68 [IQR: 60–75] years, ejection fraction 30% [IQR: 20–38], new-onset AHF 46% of the population). Twenty-one individuals formed the control group. sαKl, N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined in serum at admission and at discharge. The main clinical outcomes assessed in the study were 3-year all-cause mortality or HF rehospitalization.
Results:
sKl concentration significantly increased during episodes of AHF. A weak negative correlation was observed between sαKl and NT-proBNP at admission and discharge. Only patients with ischemic etiology of AHF did not have considerably elevated sαKl values at admission. Women and men had similar biomarker values. Smoking did not affect sαKl in our study. Patients who developed the combined endpoint during 3-year follow-up showed a smaller increase in sαKl values on admission compared to the control group (p = 0.169) and weaker biomarker kinetics during hospitalization as compared with the group free of adverse outcomes (p = 0.01).
Conclusions:
sαKl level is upregulated during an acute episode of HF and may serve as a useful biomarker. A weak reduction in sαKl levels during treatment may serve as an indicator of poor long-term prognosis.
REFERENCES (34)
1.
McDonagh TA, Metra M, Adamo M, et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42: 3599-726.
2.
Harjola VP, Mullens W, Banaszewski M, et al. Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail 2017; 19: 821-36.
3.
Zymliński R, Sokolski M, Biegus J, et al. Multi-organ dysfunction/injury on admission identifies acute heart failure patients at high risk of poor outcome. Eur J Heart Fail 2019; 21: 744-50.
4.
Zdanowicz A, Urban S, Ponikowska B, et al. Novel biomarkers of renal dysfunction and congestion in heart failure. J Pers Med 2022; 12: 898.
5.
Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997; 390: 45-51.
6.
Abraham CR, Li A. Aging-suppressor Klotho: prospects in diagnostics and therapeutics. Ageing Res Rev 2022; 82: 101766.
7.
Matsumura Y, Aizawa H, Shiraki-Iida T, et al. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 1998; 242: 626-30.
8.
Poelzl G, Ghadge SK, Messner M, et al. Klotho is upregulated in human cardiomyopathy independently of circulating Klotho levels. Sci Rep 2018; 8: 8429.
9.
Bergmark BA, Udell JA, Morrow DA, et al. Klotho, fibroblast growth factor-23, and the renin-angiotensin system – an analysis from the PEACE trial. Eur J Heart Fail 2019; 21: 462-70.
10.
Wu SE, Chen WL. Soluble klotho as an effective biomarker to characterize inflammatory states. Ann Med 2022; 54: 1520-9.
11.
Olejnik A, Franczak A, Krzywonos-Zawadzka A, Kałużna-Oleksy M, Bil-Lula I. The biological role of klotho protein in the development of cardiovascular diseases. Biomed Res Int 2018; 2018: 5171945.
12.
Prud’homme GJ, Kurt M, Wang Q. Pathobiology of the Klotho antiaging protein and therapeutic considerations. Front Aging 2022; 3: 931331.
13.
Lindner M, Mehel H, David A, et al. Fibroblast growth factor 23 decreases PDE4 expression in heart increasing the risk of cardiac arrhythmia; Klotho opposes these effects. Basic Res Cardiol 2020; 115: 51.
14.
Olejnik A, Krzywonos-Zawadzka A, Banaszkiewicz M, Bil-Lula I. Klotho protein contributes to cardioprotection during ischaemia/reperfusion injury. J Cell Mol Med 2020; 24: 6448-58.
15.
Olejnik A, Krzywonos-Zawadzka A, Banaszkiewicz M, Bil-Lula I. Klotho protein decreases MMP-mediated degradation of contractile proteins during ischaemia/reperfusion injury to the cardiomyocytes. Int J Mol Sci 2022; 23: 15450.
16.
Buckley LF, Agha AM, Dorbala P, et al. MMP-2 associates with incident heart failure and atrial fibrillation: the ARIC Study. Circ Heart Fail 2023; 16: e010849.
17.
Taneike M, Nishida M, Nakanishi K, et al. Alpha-Klotho is a novel predictor of treatment responsiveness in patients with heart failure. Sci Rep 2021; 11: 2058.
18.
Cai J, Zhang L, Chen C, et al. Association between serum Klotho concentration and heart failure in adults, a cross-sectional study from NHANES 2007-2016. Int J Cardiol 2023; 370: 236-43.
19.
Zhou L, Mo H, Miao J, et al. Klotho ameliorates kidney injury and fibrosis and normalizes blood pressure by targeting the renin-angiotensin system. Am J Pathol 2015; 185: 3211-23.
20.
Hu MC, Shi M, Gillings N, et al. Recombinant -Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy. Kidney Int 2017; 91: 1104-14.
21.
Espuch-Oliver A, Vázquez-Lorente H, Jurado-Fasoli L, et al. References values of soluble -Klotho serum levels using an enzyme-linked immunosorbent assay in healthy adults aged 18-85 years. J Clin Med 2022; 11: 2415.
22.
Pedersen L, Pedersen SM, Brasen CL, Rasmussen LM. Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays. Clin Biochem 2013; 46: 1079-83.
23.
Nie F, Wu D, Du H, et al. Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus. J Diabetes Complications 2017; 31: 594-8.
24.
Shimamura Y, Hamada K, Inoue K, et al. Serum levels of soluble secreted -Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis. Clin Exp Nephrol 2012; 16: 722-9.
25.
Kresovich JK, Bulka CM. Low serum Klotho associated with all-cause mortality among a nationally representative sample of american adults. J Gerontol A Biol Sci Med Sci 2022; 77: 452-6.
26.
Nakanishi K, Nishida M, Taneike M, et al. Implication of alpha-Klotho as the predictive factor of stress. J Investig Med 2019; 67: 1082-6.
27.
Sahu A, Mamiya H, Shinde SN, et al. Age-related declines in -Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Nat Commun 2018; 9: 4859.
28.
Bollano E, Redfors B, Rawshani A, et al. Temporal trends in characteristics and outcome of heart failure patients with and without significant coronary artery disease. ESC Heart Fail 2022; 9: 1812-22.
29.
Nawrocka-Millward S, Biegus J, Hurkacz M, et al. Differences in the biomarker profile of de novo acute heart failure versus decompensation of chronic heart failure. Biomolecules 2021; 11: 1701.
30.
Wójcicki K, Krysztofiak H, Dąbrowska K, et al. New-onset acute heart failure: clinical profile and one –year outcomes. observations from the OP-AHF Registry. Kardiol Pol 2024; 82: 210-3.
31.
Motiejūnaitė J, Akiyama E, Cohen-Solal A, et al. The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions. Eur Heart J 2020; 41: 1357-64.
32.
Nakanishi K, Nishida M, Harada M, et al. Klotho-related molecules upregulated by smoking habit in apparently healthy men: a cross-sectional study. Sci Rep 2015; 5: 14230.
33.
Onmaz M, Demirbas N, Onmaz DE, et al. Effect of cigarette smoking on serum methylarginine and -klotho levels. NMCD 2023; 33: 602-9.
34.
Nakanishi K, Nishida M, Taneike M, et al. Serum Klotho levels contribute to the prevention of disease progression. Int J Gen Med 2021; 14: 229-36.
Share
RELATED ARTICLE
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
