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The role of gut-dependent molecule trimethylamine N-oxide as a novel target for the treatment of chronic kidney disease

  • Nephrology - Review
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Abstract

Trimethylamine N-oxide (TMAO) is an intestinal uremic toxin molecule mainly excreted by the kidney. Therefore, the plasma TMAO concentration is significantly increased in chronic kidney disease (CKD) patients, and plasma TMAO can be cleared by dialysis. Furthermore, TMAO damage the kidney mainly through three mechanisms: oxidative stress, inflammation and endoplasmic reticulum stress. Clinical experiments have indicated that higher TMAO levels are strongly related to the elevated incidence and mortality of cardiovascular (CV) events in CKD patients. Moreover, experimental data have shown that high levels of TMAO directly aggravate atherosclerosis, thrombosis and enhance myocardial contractility, resulting in myocardial ischemia and stroke. Specially, there are currently four potential ways to reduce blood TMAO concentration or block the effect of TMAO, including reducing the intake of trimethylamine (TMA) precursors in the diet, regulating the intestinal flora to reduce TMA production, interrupting the role of flavin-dependent monooxygenase isoforms (FMOs) to reduce the generation of TMAO, and blocking the TMAO receptor protein kinase R-like endoplasmic reticulum kinase (PERK). We hope that more clinical studies and clinicians will focus on clinical treatment to reduce the concentration of TMAO and alleviate renal damage.

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Data Availability

Data used and/or analyzed in the current study are available upon reasonable request to the first author.

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Funding

This research was supported by Major Project of Beijing Municipal Science and Technology Commission (D181100000118004, D181100000118002) and National Key R&D Program (2018YFE0126600).

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  1. Sai Pan and Delong Zhao are co-first authors.

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  1. Medical College of the Chinese People’s Liberation Army, Department of Nephrology, General Hospital of Chinese PLA, Institute of Nephrology of Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Haidian District, Beijing, 100853, China

    Sai Pan

  2. Department of Nephrology, General Hospital of Chinese PLA, Institute of Nephrology of Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Haidian District, Beijing, 100853, China

    Delong Zhao, Shuwei Duan & Xiangmei Chen

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Pan, S., Zhao, D., Duan, S. et al. The role of gut-dependent molecule trimethylamine N-oxide as a novel target for the treatment of chronic kidney disease. Int Urol Nephrol 55, 1747–1756 (2023). https://doi.org/10.1007/s11255-023-03500-9

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