a-Klotho in Relation to Calcification in the Coronary Arteries and Aortic Valve in Patients With Chronic Kidney Disease

Chronic Kidney Diseases Clinical Trial

Official title:

Correlation of a-Klotho Levels With the Severity of Calcification in the Coronary Arteries and Aortic Valve in Patients With Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03858413
• Other study ID #: 16/23-6-2016
• Status: Completed
• Start date: January 15, 2016
• Est. completion date: December 31, 2018

Study information

• Verified date: February 2019
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To define the correlation of the levels of a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve.

Description:

Vascular calcification is a well-defined risk factor for cardiovascular disease and a-Klotho has been suggested to be an implicating factor in the process of vascular calcification, particularly in patients with chronic kidney disease (CKD).

With this study the investigators will examine the possible correlation of the levels of secreted a-Klotho with the severity of vascular calcification in the coronary arteries and aortic valve in patients with CKD at different stages of CKD. More precisely, a-Klotho was measured in 30 patients with end-stage renal disease under intermittent regular hemodialysis and 30 outpatients with stable CKD stage III (estimated glomerular filtration rate between 30 and 59 mL/min/1.73^2).

Participants in both groups were eligible only if stable for at least the last 3 months pre-enrollment. Calcification will be calculated using the well-established Agatston score after submitting all patients to multi-slice computed tomography.

Continuous variables will be described as median (25th-75th percentile) and categorical variables as N (%). Variables will be compared between groups using the non-parametric Mann-Whitney U test for continuous and Fisher's exact test for categorical variables. Bivariate correlations of a-Klotho levels with clinical variables and calcification scores using the Spearman correlation coefficient will be examined. Identification of a-Klotho determinants, log-transformation of a-Klotho levels was done because of log-normal distribution and stepwise linear regression was used, with probability to remove the variable>0.1. Identification of determinants of coronary and aortic calcification was done via log-transformation of the corresponding calcium scores, (a value of 0 was assumed; log-transformed-1 for absent calcium) and, stepwise linear regression was used as above. Because of the small sample size, all regression estimates, and confidence intervals were calculated with re-sampling so that robust variable selection and stable estimates can be ensured.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with stable chronic kidney disease stage V under intermittent hemodialysis and, patients with stable chronic kidney disease stage III

Exclusion Criteria:

• Active cancer

• Inflammatory or granulomatous disease

• Primary hyperparathyroidism

• Patients unable to provide informed consent

Related Conditions & MeSH terms

• Calcinosis
• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic
• Vascular Calcification

Intervention

Diagnostic Test:
• No intervention
No intervention

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust	AHEPA University Hospital

References & Publications (9)

Bäck M, Aranyi T, Cancela ML, Carracedo M, Conceição N, Leftheriotis G, Macrae V, Martin L, Nitschke Y, Pasch A, Quaglino D, Rutsch F, Shanahan C, Sorribas V, Szeri F, Valdivielso P, Vanakker O, Kempf H. Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet. Front Cardiovasc Med. 2019 Jan 18;5:196. doi: 10.3389/fcvm.2018.00196. eCollection 2018. Review. — View Citation

Hénaut L, Chillon JM, Kamel S, Massy ZA. Updates on the Mechanisms and the Care of Cardiovascular Calcification in Chronic Kidney Disease. Semin Nephrol. 2018 May;38(3):233-250. doi: 10.1016/j.semnephrol.2018.02.004. Review. — View Citation

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997 Nov 6;390(6655):45-51. — View Citation

Kuro-O M. The FGF23 and Klotho system beyond mineral metabolism. Clin Exp Nephrol. 2017 Mar;21(Suppl 1):64-69. doi: 10.1007/s10157-016-1357-6. Epub 2016 Nov 12. Review. — View Citation

Mencke R, Hillebrands JL; NIGRAM consortium. The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology. Ageing Res Rev. 2017 May;35:124-146. doi: 10.1016/j.arr.2016.09.001. Epub 2016 Sep 28. Review. — View Citation

Navarro-García JA, Fernández-Velasco M, Delgado C, Delgado JF, Kuro-O M, Ruilope LM, Ruiz-Hurtado G. PTH, vitamin D, and the FGF-23-klotho axis and heart: Going beyond the confines of nephrology. Eur J Clin Invest. 2018 Apr;48(4). doi: 10.1111/eci.12902. Epub 2018 Feb 21. Review. — View Citation

Olauson H, Mencke R, Hillebrands JL, Larsson TE. Tissue expression and source of circulating aKlotho. Bone. 2017 Jul;100:19-35. doi: 10.1016/j.bone.2017.03.043. Epub 2017 Mar 18. Review. — View Citation

Olejnik A, Franczak A, Krzywonos-Zawadzka A, Kaluzna-Oleksy M, Bil-Lula I. The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases. Biomed Res Int. 2018 Dec 24;2018:5171945. doi: 10.1155/2018/5171945. eCollection 2018. Review. — View Citation

Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M, Nabeshima Y. Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett. 1998 Mar 6;424(1-2):6-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Agatston score in coronary arteries.	Calcification of coronary arteries will be measured with multi-slice CT and dedicated software to calculate Agatston score.; Initially, Hounsfield units will be measured and transformed into Agatston score net numbers.; A brief description of the method is provided below: Method of calculation: The calculation is based on the weighted density score given to the highest attenuation value (HU) multiplied by the area of the calcification speck.; Density factor: 130-199 HU: 1; 200-299 HU: 2; 300-399 HU: 3; 400+ HU: 4. The score of every calcified speck is summed up to give the total calcium score.	During enrollment.
Primary	Agatston score in aortic valve.	Calcification aortic valve will be measured with multi-slice CT and dedicated software to calculate Agatston score.; Initially, Hounsfield units will be measured and transformed into Agatston score net numbers.; A brief description of the method is provided below: Method of calculation: The calculation is based on the weighted density score given to the highest attenuation value (HU) multiplied by the area of the calcification speck.; Density factor: 130-199 HU: 1; 200-299 HU: 2; 300-399 HU: 3; 400+ HU: 4. The score of every calcified speck is summed up to give the total calcium score.	During enrollment.
Primary	Circulating a-Klotho.	Circulating a-Klotho levels will be measured in serum with the use of a commercially available ELISA kit. Concentration will be expressed in pg/mL.	During enrollment.