The effect and potential mechanisms of per- and polyfluoroalkyl substances (PFAS) exposure on kidney stone risk

Exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with an increased prevalence of some kidney diseases. Kidney stones are common and have a high prevalence of kidney diseases. However, there is no evidence for the effect and potential mechanisms of PFAS on kidney stone risk. In this study, we designed a cross-sectional study using the National Health and Nutrition Examination Surveys (NHANES) data from 2017 to 2020. Our results revealed that PFAS were positively associated with kidney stone risk, and PFDA was the main contributing compound among PFAS. The triglyceride-glucose (TyG) index and the systemic immune-inflammatory (SII) index had significant mediation effects. In addition, target proteins, such as IL-6, TNF, ALB, IL-1B, and AKT1, and signaling pathways, including TNF and IL-17 pathways, might be potential mechanisms of PFAS in promoting kidney stone risk. In conclusion, PFAS, especially PFDA, increases the risk of kidney stones by the mediation effects of the TyG index and SII index. TNF and IL-17 signaling pathways may be potential mechanisms. Our findings provide new evidence for the effects and potential mechanisms of PFAS exposure in increasing kidney stone risk. However, in the future, it is still imperative to further explore and validate the underlying mechanisms of PFAS-induced kidney stone formation through experimental studies.