Kidney Risks Linked to Per‐ and Polyfluoroalkyl Substance Exposure

ABSTRACT Per‐ and polyfluoroalkyl substances (PFAS) are a large and diverse class of synthetic chemicals extensively used in industrial processes and consumer products. Human exposure to PFAS is widespread and occurs through multiple pathways, including drinking water, air, diet, household dust, textiles, cosmetics, and occupational contact, particularly with aqueous film‐forming foams. Due to their extreme environmental persistence, bioaccumulative properties, and broad biological activity, PFAS are now recognized as a major public health concern. The kidney is a primary target organ for PFAS toxicity, as it plays a central role in PFAS filtration, active tubular reabsorption, and long‐term retention. Many PFAS are inefficiently eliminated and accumulate in renal proximal tubular cells, resulting in sustained internal exposure and heightened susceptibility to renal injury. Consistent with this biological plausibility, growing epidemiological and experimental evidence links PFAS exposure to adverse kidney outcomes, including reduced glomerular filtration rate, chronic kidney disease, and nephrolithiasis. Emerging data further suggest an association between PFAS exposure and increased risk of renal malignancies, particularly renal cell carcinoma. This narrative review synthesizes and critically evaluates current evidence on PFAS‐related kidney risks, spanning functional impairment, stone formation, chronic disease progression, and cancer development. Particular emphasis is placed on the cellular and molecular mechanisms underlying PFAS‐induced nephrotoxicity, including altered renal transport, mitochondrial dysfunction, metabolic dysregulation, oxidative stress, inflammation, DNA damage, and epigenetic modifications. Finally, the review discusses potential preventive and therapeutic strategies, as well as regulatory implications for mitigating PFAS‐associated kidney disease.