Clinical, histological, molecular, and toxicokinetic renal outcomes of per-/polyfluoroalkyl substances (PFAS) exposure: Systematic review and meta-analysis

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals present in the environment that can negatively affect health. Kidney is the major target organ of PFAS exposure, yet the renal impact of PFAS is not completely understood. Here we review the effects of PFAS exposure on kidney health to identify gaps in our understanding and mark potential avenues for future research. Methods: PubMed and SCOPUS databases were searched for studies that examined the association between PFAS exposure and kidney-related outcomes. We included all epidemiological, animal, and cell studies and categorized outcomes into four categories: clinical, histological, molecular and toxicokinetic. Results: We identified 169 studies, including 51 on clinical outcomes, 28 on histological changes, 42 on molecular mechanisms, and 68 on toxicokinetics. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) exposure were associated with kidney dysfunction, chronic kidney diseases, and increased risk of kidney cancer. Various histological changes were reported, especially in tubular epithelial cells, and the etiology of PFAS-induced kidney injury included various molecular mechanisms. Although PFOA and PFOS are not considered genotoxic, they exhibit several characteristics of carcinogens. Toxicokinetics of PFOA and PFOS differed significantly between species, with renal elimination influenced by various factors such as sex, age, and structure of the compound. Conclusion: Evidence suggests that PFAS, especially PFOA and PFOS, negatively affects kidney health, though gaps in our understanding of such effects call for further research. © 2024 Elsevier Ltd