Dans quelle mesure la metformine influence-t-elle la progression de la polykystose rénale autosomique dominante ?
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- Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the progressive development of multiple renal cysts, ultimately leading to end-stage kidney failure. It results from genetic mutations causing major disturbances in cellular signaling pathways, glycolytic metabolism, autophagy, and inflammatory processes. Metformin is a widely used antidiabetic drug, well known for its effects on cellular metabolic pathways. Its mechanism of action, particularly its role in the activation of adenosine monophosphate–activated protein kinase, represents a potential therapeutic interest in the context of this disease. Thus, it appears relevant to evaluate the extent to which metformin may influence the progression of autosomal dominant polycystic kidney disease. Preclinical studies demonstrate that metformin can act on several key mechanisms involved in cyst formation and growth. It reduces intracystic fluid secretion, inhibits pathways promoting cellular proliferation, modulates glycolytic metabolism, partially restores autophagy, and attenuates inflammatory responses in various experimental models, especially when treatment is initiated at an early stage of the disease. Available clinical studies indicate that metformin has an overall favorable safety and tolerability profile in patients with ADPKD. A trend toward slowing disease progression has been observed, particularly in patients with rapidly progressive forms, although this effect did not reach statistical significance. In conclusion, despite promising mechanistic and preclinical data, current clinical evidence remains insufficient to establish a definite therapeutic benefit of metformin in ADPKD, highlighting the need for larger and longer-term clinical trials.