Abstract 18152: Targeted Mitochondrial Protection Increases the Efficacy of Stent Revascularization for Restoring Blood Flow, Tissue Oxygenation and Kidney Function in Patients With Atherosclerotic Renal Artery Stenosis
Background: Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF) and GFR and amplifies stenotic kidney (SK) hypoxia. Renal revascularization with percutaneous transluminal renal angioplasty and stenting (PTRA) often fails to recover renal function possibly due to Ischemia reperfusion injury (IRI) developing after PTRA. Elamipretide is a mitochondrial targeted peptide that reduces IRI and improves renal function when infused during PTRA in experimental models. We tested the hypothesis that Elamipretide plus PTRA would improve renal function, oxygenation and RBF in a Phase 2a, randomized, blinded, placebo-controlled pilot study in patients with ARAS undergoing PTRA.
Methods: Inpatient studies were performed during 150 mEq Na+ intake and ACE/ARB Rx in patients with severe ARAS scheduled for unilateral or bilateral PTRA. Patients were treated with a 3h IV infusion of Elamipretide (0.05 mg/kg/hour, n=6) or placebo (n=8). SK cortical/medullary perfusion and RBF were measured using contrast-enhanced multidetector CT, and renal oxygenation by 3T BOLD-MRI before and 3 months after PTRA.
Results: Age and basal GFR did not differ between the groups. Compared to baseline, BOLD imaging demonstrated substantial increases in SK hypoxia in the placebo group (n=11 kidneys) 24 hours after PTRA, which reverted to baseline 3 months later. SK-RBF and cortical perfusion increased 3 months after PTRA (p<0.05 vs. baseline) in the Elamipretide-treated group (n=10 kidneys) [figure]. Over 3 months, systolic blood pressure decreased, and eGFR increased more in the Elamipretide (from 40.7 to 46.5 ml/min, p=0.003) than in the placebo group (34.4 to 37 ml/min; p= 0.11).
Conclusion: Adjunctive Elamipretide during PTRA improved RBF, attenuated post-procedural hypoxia, and improved kidney function. These data support a role for targeted mitochondrial protection to optimize outcomes of PTRA for human ARAS.
Author Disclosures: A. Saad: None. S. Herrmann: None. A. Eirin: None. J. Woollard: None. M. McKusick: None. L. Lerman: Research Grant; Modest; Stealth Peptides International, Incorporated. S. Textor: None.
- © 2016 by American Heart Association, Inc.