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Progesterone is needed to permit adaptation of the kidney to limit potassium loss in the urines. The investigators wonder whether progesterone or other adrenal hormon play the same role. The investigators will investigate surrenal hormone production in healthy subjects under a 7-day potassium depleted diet and in patients chronically hypokalaemic due to a renal loss of potassium.
The investigators will study the adaptation of steroidogenesis to potassium depletion in healthy volunteer, and the role of progesterone in renal adaptation to potassium depletion. Practically, healthy volunteers will be submitted twice to two periods of normal Na+/ high K+ diet (control period) followed by a normal Na+/ low K+ diet sustained by a pharmacological treatment with Kayexalate (K+-depleted condition). The subjects will be treated with either RU486 or a placebo, according to a randomization. The adrenal response will be evaluated after stimulation by Synacthen at baseline and at the end of each experimental period. A Synacthen test will be also done in 10 patients suffering of chronic hypokalemia linked to a hereditary tubulopathy inducing renal K+ leak called Gitelman syndrome and their plasma steroid profile will be established.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RU 486 (mifepristone) | Experimental | Subjects will receive 400 mg once a day of RU486 |
|
| Placebo | Placebo Comparator | Subjects will receive placebo once a day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Potassium depletion | Dietary Supplement | Healthy subjects will be submitted twice at 15-30 day interval, to a low potassium diet (20mmol/day) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effect of potassium depletion on plasma progesterone (Change from Baseline of progesterone) | Healthy subjects : Change from Baseline of progesterone in response to synacthen at day 8 in subject treated by placebo. Patients with Gitelman syndrome: Change from Baseline of progesterone in response to synacthen | Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients) |
| Measure | Description | Time Frame |
|---|---|---|
| effect of RU 486 on renal adaptation to potassium depletion (Plasma potassium and kaliuresis will be monitored ) | Plasma potassium and kaliuresis will be monitored during the 7-days potassium depletion in subjects treated by RU486 or placebo, according randomization | Day 1 and day 8 of each period of treatment |
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Inclusion Criteria for healthy subjects:
Inclusion Criteria for patients :
Non inclusion Criteria for healthy subjects:
Non inclusion Criteria for Gitelman patients:
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| Name | Affiliation | Role |
|---|---|---|
| Anne Blanchard, MD, PhD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| European George Pompidou Hospital | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21326170 | Background | Elabida B, Edwards A, Salhi A, Azroyan A, Fodstad H, Meneton P, Doucet A, Bloch-Faure M, Crambert G. Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium. Kidney Int. 2011 Aug;80(3):256-62. doi: 10.1038/ki.2011.15. Epub 2011 Feb 16. | |
| 31369102 | Derived |
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| ID | Term |
|---|---|
| D053579 | Gitelman Syndrome |
| D007008 | Hypokalemia |
| ID | Term |
|---|---|
| D015499 | Renal Tubular Transport, Inborn Errors |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| Effect of potassium depletion on pulse pressure velocity (Pulse wave velocity and central blood pressure) |
Pulse wave velocity and central blood pressure are measured before and after 7 days of potassium deprivated diet. |
| At Day 1 and Day 8 of each period of treatment |
| Effect of potassium depletion on plasma progesterone under RU486 (Change from Baseline of progesterone) | Healthy subjects : Change from Baseline of progesterone in response to synacthen at day 8 in subject treated by RU486. | Day 1 and Day 8 of placebo period of treatment (healthy subjects) or once (Gitelman patients) |
| Blanchard A, Brailly Tabard S, Lamaziere A, Bergerot D, Zhygalina V, Lorthioir A, Jacques A, Hourton D, Azizi M, Crambert G. Adrenal adaptation in potassium-depleted men: role of progesterone? Nephrol Dial Transplant. 2020 Nov 1;35(11):1901-1908. doi: 10.1093/ndt/gfz135. |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |