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Abstract: FR-PO527

Metabolic Reprogramming of Renal Epithelial Cells Contributes to Lithium-Induced Nephrogenic Diabetes Insipidus

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Liu, Mi, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
  • Li, Xiulin, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
  • Deng, Mokan, University of Macau Faculty of Health Sciences, Taipa, Macao
  • Luo, Qimei, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
  • Dou, Xianrui, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
Background

Lithium, mainstay treatment for bipolar disorder, frequently causes nephrogenic diabetes insipidus (NDI). However, the detailed mechanism remains unclear. Metabolic reprogramming is not only a hallmark of disease progression, but also an important pathogenic cause and therapeutic target in diseases. But its role in Li-NDI is unknown. Rotenone (ROT), an inhibitor of electron transport complex I, has a strong protective effect in various renal diseases. Whereas, the effect of ROT on metabolic status of kidney during Li-NDI remains unknown.

Methods

Mice were treated with lithium chloride (40 mmol/kg chow) and ROT (100 ppm) in diet for 28 days. Transmission electron microscopy was performed to evaluate structural changes of nephron. Metabolomics and transcriptomics were applied to examine metabolic status during Li-NDI.

Results

ROT treatment markedly ameliorated lithium-induced NDI and mitochondrial structural abnormalities. Metabolomics and transcriptomics data demonstrated that lithium resulted in metabolic over-activation in the kidney, which were significantly ameliorated by ROT intervention.

Conclusion

Mitochondrial abnormalities and metabolic reprogramming play a key role in Li-NDI, thereby serving as a novel therapeutic target.

Funding

  • Government Support – Non-U.S.