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

NCT03858413 | Completed

• 1 other identifier: 16/23-6-2016
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Vascular Calcification; Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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.

Study Arms (2)

Chronic kidney disease stage V

No intervention

Diagnostic Test: No intervention

Chronic kidney disease stage III

No intervention

Diagnostic Test: No intervention

Interventions

No intervention DIAGNOSTIC_TEST

No intervention

Chronic kidney disease stage III; Chronic kidney disease stage V

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Two different populations have been selected. First group with patients with chronic kidney disease under hemodialysis. Second group with patients with chronic kidney disease stage III stable for the last at least 3 months

You may qualify if:

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

You may not qualify if:

• Active cancer
• Inflammatory or granulomatous disease
• Primary hyperparathyroidism
• Patients unable to provide informed consent

Sponsors & Collaborators

• Royal Brompton & Harefield NHS Foundation Trust: lead
• AHEPA University Hospital: collaborator

Related Publications (9)

• 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. doi: 10.1038/36285.

  PMID: 9363890 BACKGROUND

• 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. doi: 10.1016/s0014-5793(98)00127-6.

  PMID: 9537505 BACKGROUND

• 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.

  PMID: 30671457 BACKGROUND

• Henaut 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.

  PMID: 29753400 BACKGROUND

• 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.

  PMID: 27693241 BACKGROUND

• Navarro-Garcia JA, Fernandez-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.

  PMID: 29394451 BACKGROUND

• 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.

  PMID: 27838783 BACKGROUND

• Back M, Aranyi T, Cancela ML, Carracedo M, Conceicao 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.

  PMID: 30713844 BACKGROUND

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

  PMID: 28323144 BACKGROUND

MeSH Terms

Conditions

Vascular Calcification; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stavros Hadjimiltiades, Professor

  Head of Interventional Cardiology Department

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: February 28, 2019
• Study Start: January 15, 2016
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: February 28, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share