Ciclosporin A Preconditioning for Renal Artery Stenosis

Renal artery stenosis is one the leading cause of secondary hypertension. Previous randomized controlled trials in humans have failed to demonstrate an improvement of renal function after stenosis dilation, probably because of a selection bias with more severe patients being excluded from randomization. Renal ischemia-reperfusion injuries have also not been taken into account. Indeed, reperfusion leads to a rapid renal blood flow recovery associated with renal ischemia-reperfusion injuries.

Mitochondrial permeability transition pore (mPTP) is a key player in the occurrence of ischemia reperfusion injuries because its opening leads to mitochondria leakage and cell death. However, preconditioning whether pharmacological or ischemic can prevent mPTP opening and protect cells. Ciclosporin A can prolong mPTP closing during reperfusion and reduce renal and cardiac tissular lesions. Another mPTP blocker (Bendavia) has been associated with an improvement of renal blood flow (RBF) and glomerular filtration rate (GFR) after renal artery stenosis dilation at 6 weeks in pigs. Based on a recent study, dilation overall benefit could be secondary to an improvement of the contralateral kidney GFR and tissue oxygen content, requiring a single kidney evaluation of those renal functional parameters. The investigators previously demonstrated that dose and timing of ciclosporin A preconditioning is key to protect kidneys from ischemia-reperfusion injuries. Previous controlled trials that failed to demonstrate a benefit of ciclosporin A conditioning have used post conditioning on necrotic cells. Considering kidney ischemia-reperfusion injuries, preconditioning have led to more encouraging results compared to ciclosporin A post conditioning in animals. Therefore the investigators aim to conduct the first clinical study of ciclosporin A preconditioning for prevention of kidney ischemia-reperfusion injuries after renal artery stenosis dilation.

Using renal functional imaging and the new PET-MRI (Positron Emission Tomography-Magnetic Resonance Imaging) combined device, the investigators will evaluate kidney perfusion, oxidative metabolism, glomerular filtration rate and oxygen content before and 3 months after renal artery stenosis dilation with or without a ciclosporin A preconditioning.


Eligibility Criteria:
Inclusion Criteria:

* Patients over 50 years of age
* For women : only menopausal women
* Estimated Glomerular filtration rate ≥ 25 mL/min/1.73m2
* Renal artery stenosis with ≥ 70 % caliber reduction (Doppler or scanner or MRI)
* No controlateral stenosis
* Kidney size ≥ 7 cm
* Only atheromatous renal artery stenosis
* Resistant hypertension and/or rapid loss of kidney function and/or flash pulmonary edema
* Collective decision of dilation after a multidisciplinary meeting

Exclusion Criteria:

* Inclusion in another study
* Protected adults
* Person without a social security coverage
* Imprisoned person
* Systolic blood pressure \>180 mmHg and/or diastolic blood pressure \> 110 mmHg
* Non atheromatous renal artery stenosis
* Single kidney
* Multiple myeloma
* Iodine contrast agents allergy
* Ciclosporin A hypersensibility
* Severe other medical conditions that could be exacerbated by Iodine injection (cancer, lymphoma, active Hepatitis B, active Hepatitis C, uncontrolled HIV)
* Previous radiation exposure (above 20 mSv (millisievert) in the last 6 months before inclusion)
* MRI contra indications (MRI incompatible pacemaker or insulin pomp, metal clip, MRI incompatible cardiac valve, dental brace, claustrophobia)