Sex Hormone and Vascular Function in Women With CKD

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 the field of nephrology focuses on male patients, and studies on women's vascular health are limited. Moreover, endogenous sex hormones, particularly estradiol, are well-documented to be cardioprotective in women without CKD; however, the role of sex hormones on vascular function in women with CKD remains unclear. The goals of the proposed project are: 1) to evaluate vasuclar function in pre- and post-menopausal women with CKD vs. age-matched healthy women; 2) to evaluate sex hormone concentrations and determine whether they associate with vascular function in the proposed cohort; and 3) to gain mechanistic insight on the association between sex hormones and vascular dysfunction in the proposed cohort.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Ester S Oh, Ph.D.; Phone Number: 303-724-3765; Email: ester.oh@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Ester S Oh; Phone Number: 303-724-3765; Email: ester.oh@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Pre- and post-menopausal women with CKD vs. age-matched healthy women

Description

Inclusion Criteria:

1. Pre- (18-44 y) and post-menopausal (55-75 y) women
2. Individuals with CKD including stage 3-4 (eGFR 15-59 ml/min/1.73m2) determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
3. Controls must be healthy (free from hypertension, kidney disease, cardiovascular disease, diabetes, and other chronic disease as assessed by self-report, medical history, and screening labs). Premenopausal healthy women must have a regular menstrual cycle (25-35 d).

Exclusion Criteria:

1. Perimenopausal (45-54 y) women
2. Pregnancy, lactation, or less than one year post-partum
3. Use of hormonal birth control methods, hormone replacement therapy, or a levonorgestrel intrauterine device (IUD) insertion for a duration less than 6 months
4. Advanced CKD requiring dialysis
5. History of kidney transplant
6. Use of immunosuppressant medications (unless taking a stable dosage for a quiescent disease in CKD group)
7. Antioxidant and/or omega-3 fatty acid use within the 2 weeks prior to testing
8. Current tobacco or nicotine use or history of use in the last 12 months
9. Marijuana use within 2 weeks prior to testing
10. Uncontrolled hypertension in CKD group (BP >140/90 mmHg)
11. Atrial fibrillation
12. Active infection or antibiotic therapy
13. Hospitalization in the last month

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pre-menopausal women with CKD; Age 18-44 years CKD stage 3-4 (eGFR 15-59 ml/min/1.73m2)	Other: No intervention; No intervention
Post-menopausal women with CKD; Age 55-75 years CKD stage 3-4 (eGFR 15-59 ml/min/1.73m2)	Other: No intervention; No intervention
Pre-menopausal healthy women; Age 18-44 years Regular menstrual cycle (25-35 d)	Other: No intervention; No intervention
Post-menopausal healthy women; Age 55-75 years	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial Artery Flow-Mediated Dilation	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.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carotid Femoral Pulse Wave Velocity	A transcutaneous custom tonometer [Noninvasive Hemodynamics Workstation (NIHem), Cardiovascular Engineering Inc.] will be used to non-invasively assess carotid femoral pulse wave velocity.	Baseline
Serum Sex Hormones	Serum sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, prolactin, sex hormone binding globulin (SHBG), and anti-mullerian hormone (AMH)] will be measured using chemiluminescent assays.	Baseline
Urinary Sex Hormones	Urinary sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone-3-glucuronide (E1c), and pregnanediol-3-glucuronide (Pdg)] will be measured by by chemiluminescent assays using ACS-180 Autoanalyzer.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating/Urinary Markers of Antioxidant Status/Oxidative stress	Serum TAS, plasma/urinary 8-isoprostane, 8-OHdG will be measured using ELISA.	Baseline
Circulating Markers of Inflammation	Plasma CRP, IL-1β, IL-6, and TNF-α will be measured using ELISA	Baseline
Cytokine secretion from lipopolysaccharide(LPS)-stimulated peripheral blood mononuclear cells (PBMCs)	PBMCs will be isolated from heparinized whole blood using Cell Preparation Tube, PBMCs will be cultured with LPS, and supernatants will be harvested after 4-hour stimulation at 37°C. IL-1β, IL-6, and TNF-α in the supernatants will be measured using ELISA.	Baseline
Distribution of Monocyte Subsets	PBMCs will be stained with fluorescence-labeled antibodies for monocyte (CD14 and CD16) and analyzed using an LSR II flow cytometer.	Baseline
Ex Vivo Nitric Oxide Production from Human Umbilical Vein Endothelial Cells (HUVECs)	HUVECs will be incubated with basal media supplemented with 10% human serum collected from participants and stained with the fluorescent probe DAF-FM diacetate to detect nitric oxide production production in response to acetylcholine.	Baseline
Ex Vivo Reactive Oxygen Species Production from Human Umbilical Vein Endothelial Cells (HUVECs)	HUVECs will be incubated with basal media supplemented with 10% human serum collected from participants and stained with the fluorescent probe DAF-FM diacetate to detect reactive oxygen species production in response to acetylcholine.	Baseline

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 8, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 21-3018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with academic interest in CKD. Data shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. data use agreement) are prerequisites to the sharing of data with the requesting party.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No