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Kidney Week

Abstract: TH-OR075

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

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Aghajani Nargesi, Arash, Mayo Clinic Rochester MN, Rochester, Minnesota, United States
  • Tang, Hui, Mayo Clinic Rochester MN, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic Rochester MN, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic Rochester MN, Rochester, Minnesota, United States
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