Microplastics induce human kidney development retardation through ATP-mediated glucose metabolism rewiring

Recent research has revealed an accumulation of microplastics (MPs) in the environment and human tissues, giving rise to concerns about their potential toxicity. The kidney is a vital organ responsible for various physiological functions. Early kidney development is crucial for ensuring proper structure and function. Nevertheless, the impact of MPs on renal development is unclear. In the current study, we examined the effect of MPs on nephrogenesis using human kidney organoids. The environmentally relevant concentrations of MPs were applied. Following MP exposure, the kidney organoids exhibited reduced size and abnormal tubular structures. MPs caused an increased level of mitochondrial reactive oxygen species and DNA damage. Transcriptomic and central carbon metabolism analysis data revealed significant alterations in metabolic pathways after MP exposure, with a decrease in glycolysis and an increase in tricarboxylic acid cycle activity. Moreover, glycolysis inhibition was identified as a contributing factor to the reduced size and abnormal tubular structure of the kidney organoids. These results emphasize the negative effects of MPs on renal development through metabolic reprogramming. Our study provides a novel perspective of MP-induced nephron toxicity mechanisms. The affected pathways and metabolites identified here may act as early biomarkers and therapeutic targets for PS-MP-induced renal toxicity.