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Review ArticleReview Article

Pharmacological Targeting of Mitochondria in Diabetic Kidney Disease

Kristan H. Cleveland and Rick G. Schnellmann
John Schuetz, ASSOCIATE EDITOR
Pharmacological Reviews March 2023, 75 (2) 250-262; DOI: https://doi.org/10.1124/pharmrev.122.000560
Kristan H. Cleveland
Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (K.H.C., R.G.S.) and Southern VA Healthcare System, Tucson, Arizona (R.G.S.)
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Rick G. Schnellmann
Pharmacology and Toxicology, University of Arizona, Tucson, Arizona (K.H.C., R.G.S.) and Southern VA Healthcare System, Tucson, Arizona (R.G.S.)
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John Schuetz
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Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in the United States and many other countries. DKD occurs through a variety of pathogenic processes that are in part driven by hyperglycemia and glomerular hypertension, leading to gradual loss of kidney function and eventually progressing to ESRD. In type 2 diabetes, chronic hyperglycemia and glomerular hyperfiltration leads to glomerular and proximal tubular dysfunction. Simultaneously, mitochondrial dysfunction occurs in the early stages of hyperglycemia and has been identified as a key event in the development of DKD. Clinical management for DKD relies primarily on blood pressure and glycemic control through the use of numerous therapeutics that slow disease progression. Because mitochondrial function is key for renal health over time, therapeutics that improve mitochondrial function could be of value in different renal diseases. Increasing evidence supports the idea that targeting aspects of mitochondrial dysfunction, such as mitochondrial biogenesis and dynamics, restores mitochondrial function and improves renal function in DKD. We will review mitochondrial function in DKD and the effects of current and experimental therapeutics on mitochondrial biogenesis and homeostasis in DKD over time.

Significance Statement Diabetic kidney disease (DKD) affects 20% to 40% of patients with diabetes and has limited treatment options. Mitochondrial dysfunction has been identified as a key event in the progression of DKD, and pharmacologically restoring mitochondrial function in the early stages of DKD may be a potential therapeutic strategy in preventing disease progression.

Footnotes

    • Received January 6, 2021.
    • Accepted October 3, 2022.
  • Support was provided by The University of Arizona and Southern Arizona VA Healthcare System: [BX000851].

  • No author has an actual or perceived conflict of interest with the contents of this article.

  • dx.doi.org/10.1124/pharmrev.122.000560.

  • Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 75 (2)
Pharmacological Reviews
Vol. 75, Issue 2
1 Mar 2023
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Review ArticleReview Article

Renal Mitochondria in Diabetic Kidney Disease

Kristan H. Cleveland and Rick G. Schnellmann
Pharmacological Reviews March 1, 2023, 75 (2) 250-262; DOI: https://doi.org/10.1124/pharmrev.122.000560

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Review ArticleReview Article

Renal Mitochondria in Diabetic Kidney Disease

Kristan H. Cleveland and Rick G. Schnellmann
Pharmacological Reviews March 1, 2023, 75 (2) 250-262; DOI: https://doi.org/10.1124/pharmrev.122.000560
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  • Article
    • Visual Overview
    • Abstract
    • I. Introduction
    • II. Pathophysiology of Diabetic Kidney Disease
    • III. Treatment of Diabetic Kidney Disease
    • IV. Pharmacological Targeting of Mitochondrial Biogenesis and Dynamics
    • V. Conclusions and Further Research
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