Gender Differences in Renal Functioning and Disease

Completed

• Conditions: Chronic Renal Failure; Healthy Controls

• 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.

Study Timeline

• Study Start: 2017-05-30
• Study First Submitted: 2019-09-09
• Study First Submitted QC: 2019-09-09
• Study First Posted: 2019-09-11
• Primary Completion: 2019-12-02
• Study Completion: 2019-12-02
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-08
• Last Update Posted: 2023-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

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)

Trial Locations

Locations (1)

CHUV, nephrology service; 🇨🇭 Lausanne, Vaud, Switzerland