Ciclosporin A Preconditioning for Renal Artery Stenosis
Status:
Recruiting
Trial end date:
2022-11-01
Target enrollment:
Participant gender:
Summary
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.