Gender Differences in Renal Functioning and Disease

NCT04085094 | Completed

• 1 other identifier: 2016-01971
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the GenderBOLD study is to shed light on the mechanisms responsible for women's lower susceptibility to developing and progressing chronic renal disease, using modern imaging techniques, and applying different diets. The investigators postulate that oxygenation and renal perfusion are better conserved and change less in women than in men in different dietary situations (high salt-low salt), possibly because they are able to store excess salt in their skin and muscles. The investigators postulate that these differences are independent of their menstrual cycle. Finally, the investigators will analyze the renal functional reserve and changes in renal perfusion through an oral protein load and after sublingual nitroglycerin to assess whether potential différences exist between genders.

Conditions

Chronic Renal Failure; Healthy Controls

Keywords

BOLD-MRI; Contrast-enhanced ultrasound (CEUS); Salt storage; Perfusion index; Resistance index; Renal functional reserve; Renal oxygenation

Outcome Measures

Primary Outcomes (4)

• Change in renal microperfusion according to dietary salt intake in healthy and CKD

  Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)

  1 month (5 days high salt- two weeks wash out- 5 days low salt)

• Change in renal oxygenation after salty/unsalted diets in women compared to men

  Renal oxygenation is measured by Blood Oxygen Level Dependent (BOLD-IRM)

  1 month

• Change in skin and muscle storage of sodium according to salt intake

  Changes in cutaneous and muscle sodium storage measured by 23Na-MRI

  1 month

• Change in renal perfusion measured with CEUS after SL nitroglycerine

  Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)

  before-5 minutes after NTG

Study Arms (5)

1. Healthy and pre-menopausal women without CKD

A total of 45 healthy and pre-menopausal women (\<50 years old) will be recruited. Thirty of them are not on oral anticonception; 15 will be examined at each visit during their follicular phase, 15 during their luteal phase. Fifteen are on oral contraception. Three visits will take place: * V1: after 5 days of a high salt diet (adding 6g of salt/day on top of regular diet), patients will undergo renal ultrasound (Doppler and CEUS), renal functional MRI (BOLD and phase contrast) and Na23 muscle and skin MRI. * V2: after 5 days of low salt diet (dietary instructions), the same exams mentioned above will be repeated * V3: renal CEUS will be performed before and after an oral protein load (1g/kg) or after SL nitroglycerin (0.2mg). The day before each visit, a 24h urine collection will be performed in order to measure renal salt excretion.

Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI; Other: Pilocarpine test

2. Pre-menopausal women with CKD

A total of 30 women with CKD will be recruited and undergo the same visits as outlined above

Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI

3. Post-menopausal women without CKD

Fifteen post-menopausal women will undergo the same exams as outlined above

Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI

4. Healthy men

A total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above.

Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI; Other: Pilocarpine test

5.Men with CKD

Fifteen men with CKD will undergo the same exams as outlined above

Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI

Interventions

high-salt diet (V1) and low salt diet (V2) DIETARY_SUPPLEMENT

Before the first visit, the participant will follow a five-day high salt diet (addition of 6g/day of salt to their regular diet followed at home). Before the second visit (V2), the participant will follow for five days a low-salt diet, according to dietary instructions followed provided during the screening visit.

1. Healthy and pre-menopausal women without CKD; 2. Pre-menopausal women with CKD; 3. Post-menopausal women without CKD; 4. Healthy men

Contrast-enhanced ultrasound (CEUS) DIAGNOSTIC_TEST

Renal ultrasound with use of a contrast product (SonoVue®), perfusion rate 0.015ml/kg/min. Four destruction-reperfusion sequences are performed in order to measure the Perfusion Index (PI) of the renal cortex.

1. Healthy and pre-menopausal women without CKD; 2. Pre-menopausal women with CKD; 3. Post-menopausal women without CKD; 4. Healthy men; 5.Men with CKD

functional MRI DIAGNOSTIC_TEST

Measurement of renal oxygenation with the Blood Oxygenation Level Dependant-MRI technique (BOLD-MRI) on Siemens Prisma 3T scanner before and 15minutes after 0.03mg/kg of IV furosemide. Assessment of the amount of salt stored in the skin and muscles with the 23Na MRI technique.

1. Healthy and pre-menopausal women without CKD; 2. Pre-menopausal women with CKD; 3. Post-menopausal women without CKD; 4. Healthy men; 5.Men with CKD

Pilocarpine test OTHER

Assessment of sweat salt and potassium concentrations in healthy volunteers according to slat intake. Two electrodes are placed on the forearm. The electric current between the two electrodes will induce perspiration which will be collected with the Macroduct system.

1. Healthy and pre-menopausal women without CKD; 4. Healthy men

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The study is characterized by several groups which contain only men or only women.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers will be recruited by way of advertisement at CHUV. Patients with CKD will be recruited via the ambulatory nephrology consultation.

You may not qualify if:

• Age ≥ 18 years old and \<50 years old.
• No drugs (psychoactive substances used for non-medical purposes) /medicine.
• Blood pressure \<135/85mmHg.
• Renal function (eGFR \>90ml/min/1.73m2) and absence of albuminuria.
• Regular menstrual cycle.
• No pregnancy.
• Understanding and signature of the informed consent.
• Age ≥ 18 years old and \<50 years old.
• Possibility to stop the treatment during the day of the study.
• Reduced renal function (eGFR 15-60 ml/min/1.73m2) or eGFR 60-90 ml/min/1.73m2 with the presence of albuminuria \>300 mg/j.
• Understanding and signature of the informed consent.
• Age ≥ 50 years old.
• Absence of menstruation.
• No drugs consumption.
• No medicine, or possibility to stop it two days before the study.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead
• University Hospital, Geneva: collaborator

Study Sites (1)

CHUV, nephrology service

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Collection of blood samples (all), urine (all) and sweat in some.

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

myotrophin; Diet, Sodium-Restricted; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; 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

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Menno Pruijm, PD MD

  CHUV

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 11, 2019
• Study Start: May 30, 2017
• Primary Completion: December 2, 2019
• Study Completion: December 2, 2019
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)