Gender Differences in Renal Functioning and Disease

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.

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.

Eligibility 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.

Exclusion criteria for all:

* Contra-indication for Magnetic Resonance Imaging (Pacemaker, implanted metallic device, claustrophobia,..)
* Known allergy to one of the study compounds (furosemide, Sonovue).

Exclusion criteria for persons with chronic renal failure:

* Autosomal dominant polycystic kidney disease.
* Ingestion of corticosteroids or other immunosuppressants.
* Volume overload or heart failure.
* eGFR \< 15ml/min/1.73m2 or dialysis.

Exclusion criteria for men and women receiving sublingual nitroglycerin:

* Hypersensitivity to nitrous derivatives or to one of the excipients present in the composition.
* History of heart disease (ischemic heart disease, valve and/or rhythmic).
* Low blood pressure (systolic blood pressure \<100mmHg)