Kidney Week

Abstract: TH-OR075

Renal Artery Stenosis Magnifies Mitochondrial Damage, Aggravating Post-Stenotic Kidney Injury in Pigs with Metabolic Syndrome

Session Information

• Hypertension and CVD: Basic Mechanisms
  October 25, 2018 | Location: 6F, San Diego Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Aghajani Nargesi, Arash, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Arash Aghajani Nargesi, MD, MPH



Arash Aghajani Nargesi is a post-doctoral research fellow at Renovascular Research Laboratory, Mayo Clinic Rochester. He was graduated with MD-MPH degree from Tehran University of Medical Sciences, Tehran, Iran. His research aims to better understand the underlying mechanisms of kidney dysfunction in patients with metabolic syndrome and renal artery stenosis. He hopes to develop regenerative treatments for renovascular and cardiovascular diseases. He is a recipient of American Heart Association (AHA) post-doctoral fellowship award.

• Tang, Hui, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Hui Tang,

• Lerman, Lilach O., Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Lilach O. Lerman,

• Eirin, Alfonso, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Alfonso Eirin,

Background

Renal artery stenosis (RAS) often develops in the context of prevalent cardiovascular risk factors, and can induce hypertension, renal injury, and fibrosis. We have shown that metabolic syndrome (MetS) induces mitochondrial damage associated with glomerular hyperfiltration and tubular injury. We hypothesized that superimposition of RAS on MetS would exacerbate mitochondrial damage, aggravating post-stenotic kidney injury in swine.

Methods

Domestic pigs were studied after 16 weeks of either high-fat/high-fructose or standard diet with or without superimposed RAS (n=7 each). Single-kidney GFR was assessed in-vivo with multi-detector-CT, and renal tubular mitochondrial morphology ex vivo by electron microscopy. ATP production was measured by colorimetric/fluorimetric methods in isolated mitochondria and renal fibrosis by trichrome staining.

Results

Blood pressure was higher in MetS, Lean+RAS, and MetS+RAS compared to Lean (Table). Both RAS groups achieved significant stenosis. Single-kidney GFR was higher in MetS vs Lean, but decreased in Lean+RAS and MetS+RAS vs. their respective controls. MetS+RAS further decreased renal mitochondrial matrix density (Fig. B-C) and ATP production (Fig. D), and increased renal fibrosis (Fig. E) compared to Lean+RAS.

Conclusion

RAS superimposed on MetS aggravates mitochondrial structural damage and dysfunction, which may contribute to structural injury and dysfunction in the post-stenotic kidney.

Funding

• NIDDK Support