Exposure to phthalates and environmental phenols in association with chronic kidney disease (CKD) among the general US population participating in multi-cycle NHANES (2005-2016)

Abstract

Exposure to consumer chemicals has been associated with chronic kidney disease (CKD) among humans, but their associations with estimated glomerular filtration rate (eGFR) are inconsistent. Such observations may be due to potential bias caused by the method of urine dilution adjustment and lack of consideration for multiple chemical exposure in the association models. This study aimed to identify major urinary chemicals associated with CKD by applying an alternative adjustment method of urine dilution ('novel' covariate-adjusted creatinine adjustment vs 'traditional' creatinine adjustment) and with a mixture exposure concept in the association model. For this purpose, the adult participants of US National Health and Nutrition Examination Survey (NHANES) 2005-2016 (n = 9008) were used, and the associations of urinary exposure biomarkers of major consumer chemicals, e.g., phthalates, bisphenol A, benzophenone-3, and parabens, with CKD related parameters of eGFR and albumin-to-creatinine ratio (ACR), were assessed. The use of the novel covariate-adjusted creatinine standardization resulted in significant inverse associations with eGFR for most measured chemicals, unlike the results with the use of the conventional creatinine adjustment. Phthalate metabolites, such as monobutyl phthalate (MBP) and mono-benzyl phthalate (MBzP), were positively associated with ACR. Even in mixture exposure models using weighted quantile sum (WQS) regression, MBzP, metabolites of di-(2-ethylhexyl) phthalate (DEHP), and bisphenol A (BPA) were revealed as major drivers of the association with eGFR or ACR. Results of sensitivity analyses with the subpopulation with normal eGFR range (n = 7041) were generally similar. Our observation suggests that exposure to benzyl butyl phthalate (BBP), DEHP, and BPA may be responsible for declined eGFR and increased ACR even at the exposure levels occurring among general adults.

Keywords: Albuminuria; Bisphenol A (BPA); Creatinine; Glomerular filtration rate (GFR); Plasticizer.