Chronic Kidney Diseases
Conditions
Brief summary
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.
Interventions
OTHERNo intervention
No intervention
Sponsors
University of Colorado, Denver
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
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 AND/OR urinary albumin-creatinine ratio (UACR) ≥ 30. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial Artery Flow-Mediated Dilation | Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Carotid Femoral Pulse Wave Velocity | Baseline | A transcutaneous custom tonometer \[Noninvasive Hemodynamics Workstation (NIHem), Cardiovascular Engineering Inc.\] will be used to non-invasively assess carotid femoral pulse wave velocity. |
| Serum Sex Hormones | Baseline | 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. |
| Urinary Sex Hormones | Baseline | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ex Vivo Nitric Oxide Production from Human Umbilical Vein Endothelial Cells (HUVECs) | Baseline | 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. |
| Circulating/Urinary Markers of Antioxidant Status/Oxidative stress | Baseline | Serum TAS, plasma/urinary 8-isoprostane, 8-OHdG will be measured using ELISA. |
| Ex Vivo Reactive Oxygen Species Production from Human Umbilical Vein Endothelial Cells (HUVECs) | Baseline | 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. |
| Circulating Markers of Inflammation | Baseline | Plasma CRP, IL-1β, IL-6, and TNF-α will be measured using ELISA |
| Cytokine secretion from lipopolysaccharide(LPS)-stimulated peripheral blood mononuclear cells (PBMCs) | Baseline | 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. |
| Distribution of Monocyte Subsets | Baseline | PBMCs will be stained with fluorescence-labeled antibodies for monocyte (CD14 and CD16) and analyzed using an LSR II flow cytometer. |
Countries
United States
Outcome results
None listed