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Kidney Week

Abstract: SA-PO991

Quantitative In Situ Assessments of Mitochondrial Impairment Are Associated With Progressive Kidney Disease

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Huang, Huihui, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Zsengeller, Zsuzsanna Kinga, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Jotwani, Vasantha, University of California San Francisco, San Francisco, California, United States
  • Thiessen Philbrook, Heather, Johns Hopkins University, Baltimore, Maryland, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Ix, Joachim H., University of California San Diego, La Jolla, California, United States
  • Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States
  • Arking, Dan, Johns Hopkins University, Baltimore, Maryland, United States
  • Sarnak, Mark J., Tufts University, Medford, Massachusetts, United States
  • Shlipak, Michael, University of California San Francisco, San Francisco, California, United States
  • Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
  • Parikh, Samir M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Mitochondrial impairment in the kidney tubule has been experimentally linked to the progression of chronic kidney disease (CKD). However, the relationships among in situ assessments of mitochondrial abundance, biogenesis capacity and oxidative phosphorylation and classical histopathological features remain under-explored in human CKD.

Methods

Among voluntary participants in a nephrectomy cohort for renal cell cancer who contributed non-tumor specimens to a CKD biorepository (n=42), we undertook blinded quantitative histochemical evaluation of several features related to mitochondria: immunostaining for mitochondrially encoded cytochrome C oxidase I (MTCO1) to assess mitochondrial abundance; PPAR-gamma-coactivator-1-alpha (PGC1a) to assess biogenesis capacity; and enzyme histochemistry for cytochrome C oxidase (COX-EHC) to assess mitochondrial oxidative phosphorylation. ImageJ was used to score staining intensity in ten randomly selected high-power fields per assessment, and the mean score was obtained from each specimen for the three mitochondrial assessments. These scores were compared to estimated glomerular filtration rate (eGFR) and to blinded semiquantitative assessments of glomerulosclerosis (GLOMSCL), arteriosclerosis (ARTSCL), and interstitial fibrosis/tubular atrophy (IFTA).

Results

The mean age was 61±11 years and the mean eGFR was 68±22 ml/min/1.73m2. The three mitochondrial parameters were significantly inter-correlated and were directly correlated with eGFR (Figure). COX-EHC was significantly and inversely correlated to GLOMSCL, ARTSCL, and IFTA. Conversely, IFTA was inversely correlated to all three mitochondrial assessments.

Conclusion

Quantitative in situ assessments of mitochondrial abundance, biogenesis, and oxidative phosphorylation are significantly correlated with functional and histopathological hallmarks of kidney disease. These results suggest that progressive mitochondrial impairments may be intimately linked to worsening kidney disease.

Funding

  • NIDDK Support