Chronic Renal Failure, Healthy Controls
Conditions
Keywords
BOLD-MRI, Contrast-enhanced ultrasound (CEUS), Salt storage, Perfusion index, Resistance index, Renal functional reserve, Renal oxygenation
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.
Interventions
OTHERPilocarpine test
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.
DIETARY_SUPPLEMENThigh-salt diet (V1) and low salt diet (V2)
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.
DIAGNOSTIC_TESTContrast-enhanced ultrasound (CEUS)
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.
DIAGNOSTIC_TESTfunctional MRI
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.
Sponsors
University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion/
Exclusion criteria
Inclusion criteria for healthy pre-menopausal women: * 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. Inclusion criteria for pre-menopausal women with a chronic renal failure: * 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. Inclusion criteria for post-menopausal women: * Age ≥ 50 years old. * Absence of menstruation. * No drugs consumption. * No medicine, or possibility to stop it two days before the study. * Blood pressure \<135/85mmHg. * Renal function (eGFR \>90ml/min/1.73m2) and absence of albuminuria. * Understanding and signature of the informed consent. Inclusion criteria for men: * Age ≥ 18 years old, but matched with the age of pre- aor post-menopausal women * No drugs consumption. * No medicine, or possibility to stop it two days before the study. * Blood pressure \<135/85mmHg. * Renal function (eGFR \>90ml/min/1.73m2) and absence of albuminuria. * Understanding and signature of the informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
Countries
Switzerland
Outcome results
None listed