Several publications from 2023 have substantiated the importance of altered NAD synthesis in kidney injury and disease progression. Now, NAD deficiency has been linked to the release of mitochondrial RNA and activation of pathways that induce inflammation. Another enzyme that governs mitochondrial function, PCK1, has also now been linked to kidney disease.
Key advances
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Analyses of kidney biopsy samples from humans and mice have shown that alterations in NAD synthesis in the context of kidney injury leads to mitochondrial dysfunction and mitochondrial RNA release, which triggers the RIG-I pathway and inflammation2
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Transcriptome analyses suggest that differences in the susceptibility of mouse strains to kidney injury may in part relate to the severity of mitochondrial injury and extent of NAD synthesis dysregulation3
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Nicotinamide riboside supplementation might modify systemic mitochondrial metabolism in patients with chronic kidney disease (CKD)6
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PCK1, a gluconeogenic enzyme that is downregulated during acute kidney injury and CKD, is a key novel regulator of metabolism, acid–base equilibrium and mitochondrial function in the kidney4,5
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References
Clark, A. J., Saade, M. C. & Parikh, S. M. The significance of NAD+ biosynthesis alterations in acute kidney injury. Semin. Nephrol. 42, 151287 (2022).
Doke, T. et al. NAD+ precursor supplementation prevents mtRNA/RIG-I-dependent inflammation during kidney injury. Nat. Metab. 5, 414–430 (2023).
Morel, J.-D. et al. Mitochondrial and NAD+ metabolism predict recovery from acute kidney injury in a diverse mouse population. JCI Insight 8, e164626 (2023).
Verissimo, T. et al. PCK1 is a key regulator of metabolic and mitochondrial functions in renal tubular cells. Am. J. Physiol. Renal Physiol. 324, F532–F543 (2023).
Hasegawa, K., Sakamaki, Y., Tamaki, M. & Wakino, S. PCK1 protects against mitoribosomal defects in diabetic nephropathy in mouse models. J. Am. Soc. Nephrol. 34, 1343–1365 (2023).
Ahmadi, A. et al. Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease. JCI Insight 8, e167274 (2023).
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Verissimo, T., de Seigneux, S. New evidence of the impact of mitochondria on kidney health and disease. Nat Rev Nephrol 20, 81–82 (2024). https://doi.org/10.1038/s41581-023-00803-z
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DOI: https://doi.org/10.1038/s41581-023-00803-z
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