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

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

Detailed Description
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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.

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

Conditions
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Vascular Calcification, Chronic Kidney Diseases

Intervention / Treatment
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* Diagnostic Test: No intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic kidney disease stage V<br>No intervention | Diagnostic Test: No intervention<br>* No intervention<br>|
| Chronic kidney disease stage III<br>No intervention | Diagnostic Test: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |