Gender Differences in Renal Functioning and Disease

NCT ID: NCT04085094

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 98 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-05-30
• Study Completion Date: 2019-12-02

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.

Conditions

Chronic Renal Failure; Healthy Controls

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

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

Intervention Type: 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.

Contrast-enhanced ultrasound (CEUS)

Intervention Type: 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.

functional MRI

Intervention Type: 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.

Pilocarpine test

Intervention Type: 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.

2. Pre-menopausal women with CKD

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

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

Intervention Type: 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.

Contrast-enhanced ultrasound (CEUS)

Intervention Type: 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.

functional MRI

Intervention Type: 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.

3. Post-menopausal women without CKD

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

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

Intervention Type: 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.

Contrast-enhanced ultrasound (CEUS)

Intervention Type: 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.

functional MRI

Intervention Type: 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.

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.

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

Intervention Type: 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.

Contrast-enhanced ultrasound (CEUS)

Intervention Type: 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.

functional MRI

Intervention Type: 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.

Pilocarpine test

Intervention Type: 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.

5.Men with CKD

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

Contrast-enhanced ultrasound (CEUS)

Intervention Type: 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.

functional MRI

Intervention Type: 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.

Interventions

high-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.

Intervention Type: DIETARY_SUPPLEMENT

Contrast-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.

Intervention Type: DIAGNOSTIC_TEST

functional 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.

Intervention Type: DIAGNOSTIC_TEST

Pilocarpine 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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.
• Blood pressure <135/85mmHg.
• Renal function (eGFR >90ml/min/1.73m2) and absence of albuminuria.
• Understanding and signature of the informed consent.

• 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

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

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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Geneva

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire Vaudois

OTHER

Sponsor Role: lead

Responsible Party

Gregoire Wuerzner; MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Menno Pruijm, PD MD

Role: PRINCIPAL_INVESTIGATOR

CHUV

Locations

CHUV, nephrology service

Lausanne, Canton of Vaud, Switzerland

Countries

Switzerland

Other Identifiers

2016-01971

Identifier Type: -

Identifier Source: org_study_id