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Diabetic kidney disease in 2024

Mitochondrial dysfunction has a central role in diabetic kidney disease

Nature Reviews Nephrology volume 21, pages 77–78 (2025)Cite this article

Subjects

Diabetic kidney disease (DKD), the most common cause of chronic kidney disease, is primarily caused by metabolic dysfunction, likely due to mitochondrial abnormalities. In 2024, several studies made important strides towards defining the molecular mechanisms that underlie the development of DKD.

Key advances

  • A multi-omic and spatial metabolomic analysis of human kidney samples identified a defect in fatty acid oxidation in proximal tubule cells from people with kidney disease2.

  • An analysis of kidney biopsy samples from young adults with type 1 diabetes mellitus identified reduced oxidative metabolism and tricarboxylic acid cycle disruption before the development of albuminuria5.

  • Elevated levels of urinary lactate, a biomarker of mitochondrial dysfunction, were associated with kidney function decline in large cohorts of patients with diabetic kidney disease (DKD)6.

  • Mitochondrial proteome profiling of podocytes showed that NDUFS4 stabilizes respiratory supercomplexes; in diabetic mice, reduced levels of NDUFS4 led to compromised mitochondrial function, potentially contributing to DKD progression7.

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Fig. 1: The impact of mitochondrial dysfunction and metabolic disorders on DKD progression.

References

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Authors and Affiliations

  1. Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA

    Shen Li & Katalin Susztak

  2. Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Shen Li & Katalin Susztak

  3. Penn/CHOP Kidney Innovation Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Shen Li & Katalin Susztak

  4. Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA

    Katalin Susztak

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  1. Shen Li
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  2. Katalin Susztak
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Correspondence to Katalin Susztak.

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The authors declare no competing interests.

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Li, S., Susztak, K. Mitochondrial dysfunction has a central role in diabetic kidney disease. Nat Rev Nephrol 21, 77–78 (2025). https://doi.org/10.1038/s41581-024-00919-w

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