Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk

Zhiping Niu; Zhizhou Duan; Weixiang He; Tianyi Chen; Hao Tang; Shuang Du; Jin Sun; Han Chen; Yuanzhuo Hu; Yuka Iijima; Shichao Han; Jiufeng Li; Zhuohui Zhao

doi:10.1016/j.jhazmat.2024.134312

Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk

J Hazard Mater. 2024 Apr 16:471:134312. doi: 10.1016/j.jhazmat.2024.134312. Online ahead of print.

Authors

Zhiping Niu¹, Zhizhou Duan², Weixiang He³, Tianyi Chen¹, Hao Tang¹, Shuang Du¹, Jin Sun¹, Han Chen¹, Yuanzhuo Hu¹, Yuka Iijima⁴, Shichao Han⁵, Jiufeng Li⁶, Zhuohui Zhao⁷

Affiliations

¹ Department of Environmental Health, School of Public Health, NHC Key Laboratory of Health Technology Assessment, Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
² Preventive Health Service, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, 152 Aiguo Road, Nanchang, Jiangxi, China.
³ Department of Urology, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China.
⁴ Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁵ Department of Urology, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China. Electronic address: hanshichaohome@163.com.
⁶ Department of Environmental Health, School of Public Health, NHC Key Laboratory of Health Technology Assessment, Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China. Electronic address: lijiufeng@fudan.edu.cn.
⁷ Department of Environmental Health, School of Public Health, NHC Key Laboratory of Health Technology Assessment, Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China; Shanghai Typhoon Institute/CMA, Shanghai Key Laboratory of Meteorology and Health, Shanghai 200030, China; IRDR International Center of Excellence on Risk Interconnectivity and Governance on Weather/Climate Extremes Impact and Public Health, Fudan University, Shanghai 200438, China; WMO/IGAC MAP-AQ Asian Office Shanghai, Fudan University, Shanghai 200438, China. Electronic address: zhzhao@fudan.edu.cn.

PMID: 38640681
DOI: 10.1016/j.jhazmat.2024.134312

Abstract

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003-2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.

Keywords: Estimated glomerular filtration rate; Hyperuricemia; Kidney function; PFAS; Per- and poly-fluoroalkyl substance; Uric acid.