The risk of cardiovascular disease (CVD) is significantly elevated in patients with chronic kidney disease (CKD). Notably, women with CKD commonly experience menstrual disturbances induced by CKD, which may contribute to impaired vascular function and elevated CVD risk. However, most of the literature in nephrology focuses on male patients, and studies on women's vascular health are limited. Establishing effective therapies for improving vascular function and reducing CVD risk in women with CKD is a high research priority of the NIH.
Equol contributes to improvement in vascular function, mediated in part by its anti-oxidative and anti-inflammatory properties. However, there is no information on the effect of equol on vascular function in women with CKD. The proposed project aims to determine the effect of 12 weeks of oral equol supplementation on vascular function in postmenopausal women with CKD.
Postmenopausal women
Aged ≥50 years
CKD stage 3 or 4 (eGFR with the CKD-EPI 2021 race-free equation: 15-59 mL/min/1.73m2; stable renal function in the past 3 months)
Low habitual intake of soy (soy-related food intake < 2 times per week assessed by Soy-Specific Food Frequency Questionnaire)
Patients with advanced CKD requiring chronic dialysis
Uncontrolled hypertension in CKD group (BP >140/90 mmHg)
Use of any hormone replacement therapy
Allergy and/or intolerance to soy or soy-based products
Parallel
Equol
DrugThis group will receive 10 mg equol per day (2 capsules/day, 5mg equol/capsule).
Placebo
DrugThis group will receive 2 placebo capsules per day.
Brachial Artery Flow-Mediated Dilation (FMDBA)
Flow-mediated dilation of the brachial artery will be performed using ultrasonography and analyzed with a commercially available software package as percent change in diameter from baseline following reactive hyperemia.
Carotid-Femoral Pulse Wave Velocity (CFPWV)
A transcutaneous tonometer (Noninvasive Hemodynamics Workstation, Cardiovascular Engineering Inc.) will be positioned at the carotid and femoral arteries, and CFPWV will be calculated as the mean distance/time between the foot of the carotid and femoral arterial waveforms calculated over \>30 heart cycles. Data will be expressed as m/s.
Casual blood pressure
Casual (resting) measures of systolic blood pressure (mmHg) will be measured in triplicate over the brachial artery of the non-dominant arm after 5 minutes of quiet rest, with 1 minute of recovery between each measure, using an automated oscillometric sphygmomanometer.
Carotid artery compliance
Carotid compliance will be calculated using arterial blood volume and change in arterial blood pressure, which provides an index of local arterial stiffness. Unit: mm/mm Hg×10-1; there is no minimum or maximum; higher values indicate better function.
Beta-stiffness index
Beta-stiffness index will be calculated using systolic and diastolic pressure, blood viscosity, and pulse pressure, which provides an index of local arterial stiffness. Unit: A.U.; there is no minimum or maximum; higher values indicate worse function.
24-Hour Ambulatory Systolic Blood Pressure
Brachial artery systolic blood pressure (mmHg) will be measured automatically every 20 minutes for a 24-hour period by an ambulatory blood pressure monitor and will be averaged over the entire 24-hour period.
Endothelial Cell Protein Expression
Endothelial cells will be obtained from peripheral veins via endovascular biopsy. Cells will be recovered by centrifugation, fixed with paraformaldehyde, and slides will be prepared and frozen. Slides will be stained for the primary antibody of interest and a complementary fluorescent secondary Alexafluor 657 antibody (Invitrogen). Slides will also be stained for the extracellular domain of vascular endothelial cadherin (Abcam) for positive identification of endothelial phenotype and DAPI for nuclear integrity. Images will be digitally captured and analyzed using Image J software (NIH). Values will be reported as ratios of subject endothelial cell protein expression to human umbilical vein endothelial cell (HUVEC) control cell protein expression. The abundance or expression of the following markers will be determined: NOX1, ERK1/2, eNOS, and phospho-eNOS (Ser1177).
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
