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Moreover, the accumulation of deleterious microbial metabolitesincluding indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO)exerts direct nephrotoxic effects through sophisticated mechanisms involving epigenetic dysregulation and oxidative stress amplification, establishing a self-perpetuating pathological feedback circuit of aberrant gut-kidney crosstalk (Alvarenga et al., 2025)

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