Background: Long-term exposure to fine particulate matter (PM2.5) is increasingly recognized as a risk factor for chronic kidney disease (CKD). We previously demonstrated that high-dose PM2.5 exposure prior to ischemia/reperfusion injury (IRI) aggravates acute kidney injury (AKI). Here, we investigated how prolonged, low concentration urban PM2.5 exposure affects kidney repair after AKI. Methods: Six-week-old mice underwent bilateral IRI or sham surgery, followed by six months of exposure to either filtered air or ambient PM2.5 exposure in a unique exposome chamber. Kidneys were analyzed using pathomics, electron and super resolution microscopy, immunohistochemistry, transcriptomics, and LC/MS-based lipidomics and metabolomics. Complementary in vitro hypoxia/reoxygenation and PM2.5 exposure experiments were performed in proximal tubular epithelial cells. Results: Long term PM2.5 exposure had minimal effects in sham operated mice, including no significant changes in body weight or kidney function. Despite preserved kidney function, IRI+PM2.5 mice exhibited reduced weight gain, a marked expansion of the interstitial area, attributable to enhanced fibrosis and inflammatory responses, microvascular rarefaction, and endothelial-to-mesenchymal transition, consistent with maladaptive repair features. Proximal tubules displayed mitochondrial injury, glycolytic reprogramming, lipid accumulation, and a senescent phenotype. Energy Dispersive X ray (EDX) microscopy confirmed PM2.5 derived elements within proximal tubules lysosomes, accompanied by lysosomal stress. Drug screening based on transcriptional signature identified nicotinamide as a compound capable of reversing PM2.5 induced metabolic alterations; in vitro validation confirmed rescue of mitochondrial function in injured p