To investigate the nephrotoxicity of polybutylene adipate-co-terephthalate (PBAT)-modified starch composite material, substances migrating to different food simulants (4% acetic acid, 10% ethanol, and 95% ethanol) from the composite material were prepared and evaluated for its toxicity in human renal proximal tubule epithelial (HK-2) cells by analyzing the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway and the expression levels of silent information regulator sirtuin 1 (SIRT1), peroxisome proliferators-activated receptor γ coactivator-l alpha (PGC-1α), nuclear respiratory factor-1 (NRF1) and recombinant transcription factor A (TFAM). The results showed that the migrants increased the expression level of kidney injury molecule-1 (KIM-1), elevated inflammatory factor levels and decreased antioxidant factor levels in HK-2 cells. The migrants upregulated the p-AMPK/AMPK ratio in HK-2 cells, and downregulated the p-mTOR/mTOR ratio as well as the expression levels of SIRT1, PGC-1α, NRF1, and TFAM. In summary, the migrants from the composite material could induce oxidative stress and inflammation in HK-2 cells. Furthermore, it might lead to mitochondrial dysfunction through the AMPK signaling pathway, resulting in kidney damage and posing a potential threat to human health
