Gender Differences in Renal Functioning and Disease
- Conditions
- Chronic Renal FailureHealthy Controls
- Interventions
- Dietary Supplement: high-salt diet (V1) and low salt diet (V2)Diagnostic Test: Contrast-enhanced ultrasound (CEUS)Diagnostic Test: functional MRIOther: Pilocarpine test
- Registration Number
- NCT04085094
- Lead Sponsor
- Centre Hospitalier Universitaire Vaudois
- 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.
- Detailed Description
Chronic kidney disease (CKD) affects about 10% of the adult population in Switzerland.
Despite decades of research, the mechanisms involved in the development and progression of CKD remain unclear, and there is a lack of preventative therapies. Women are relatively protected against CKD, but this topic has been little studied.
The kidney is very sensitive to hypoxia and its chronic oxygen depravation is the final step in the pathogenesis of CKD. A special MRI application, called BOLD-MRI, has the ability to measure renal tissue oxygenation in humans. In a recent BOLD-MRI study, the investigators demonstrated that cortical oxygenation is significantly higher in women than in men, which may explain women's lower susceptibility to declining renal function. However, whether this is true under different dietary conditions (high salt-low salt), and whether renal oxygenation changes throughout the menstrual cycle is unknown and will be assessed in this study.
Renal oxygenation depends on its perfusion. Renal micro-perfusion can be measured with contrast-enhanced ultrasound (CEUS) and is expressed as PI (perfusion index). CEUS is a recent imaging technique that combines conventional ultrasound with the administration of a microbubble contrast agent (a lipid or albumin-enveloped gas compound). The microbubbles are inert and eliminated by pulmonary and hepatic systems within one hour of administration. They are not nephrotoxic and have no major side effects. Whether there are differences in renal perfusion as measured with CEUS between men and women with and without CKD will be also assessed in this study.
Oxygenation of the kidneys does not only depend on their perfusion, but also on their consumption, mainly related to tubular active sodium transport. Thus, their oxygenation is lower in the case of a high salt diet compared to a low salt diet. This has been proven in men, but not in women.
Recently, another MRI technique called 23Na MRI was used to measure the amount of salt stored in the skin and muscles. It is possible that the cutaneous and muscular capacity of storing salt according to dietary salt intake is lower in men, but this has not, at present, been examined.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 2. Pre-menopausal women with CKD Contrast-enhanced ultrasound (CEUS) A total of 30 women with CKD will be recruited and undergo the same visits as outlined above 2. Pre-menopausal women with CKD functional MRI A total of 30 women with CKD will be recruited and undergo the same visits as outlined above 3. Post-menopausal women without CKD Contrast-enhanced ultrasound (CEUS) Fifteen post-menopausal women will undergo the same exams as outlined above 4. Healthy men Contrast-enhanced ultrasound (CEUS) A total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above. 4. Healthy men functional MRI A total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above. 5.Men with CKD Contrast-enhanced ultrasound (CEUS) Fifteen men with CKD will undergo the same exams as outlined above 1. Healthy and pre-menopausal women without CKD high-salt diet (V1) and low salt diet (V2) 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. 2. Pre-menopausal women with CKD high-salt diet (V1) and low salt diet (V2) A total of 30 women with CKD will be recruited and undergo the same visits as outlined above 3. Post-menopausal women without CKD functional MRI Fifteen post-menopausal women will undergo the same exams as outlined above 1. Healthy and pre-menopausal women without CKD Contrast-enhanced ultrasound (CEUS) 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. 1. Healthy and pre-menopausal women without CKD Pilocarpine test 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. 4. Healthy men high-salt diet (V1) and low salt diet (V2) A total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above. 1. Healthy and pre-menopausal women without CKD functional MRI 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. 3. Post-menopausal women without CKD high-salt diet (V1) and low salt diet (V2) Fifteen post-menopausal women will undergo the same exams as outlined above 4. Healthy men Pilocarpine test A total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above. 5.Men with CKD functional MRI Fifteen men with CKD will undergo the same exams as outlined above
- Primary Outcome Measures
Name Time Method Change in renal microperfusion according to dietary salt intake in healthy and CKD 1 month (5 days high salt- two weeks wash out- 5 days low salt) Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)
Change in skin and muscle storage of sodium according to salt intake 1 month Changes in cutaneous and muscle sodium storage measured by 23Na-MRI
Change in renal perfusion measured with CEUS after SL nitroglycerine before-5 minutes after NTG Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)
Change in renal oxygenation after salty/unsalted diets in women compared to men 1 month Renal oxygenation is measured by Blood Oxygen Level Dependent (BOLD-IRM)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
CHUV, nephrology service
🇨🇭Lausanne, Vaud, Switzerland