Per- and polyfluoroalkyl substances (PFAS) Accumulation in CKD: The Hidden Role of Albuminuria in Modifying Environmental Toxin Burden

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Per- and polyfluoroalkyl substances (PFAS) Accumulation in CKD: The Hidden Role of Albuminuria in Modifying Environmental Toxin Burden

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Co-author 1

Ping-Hsun Wu 970392kmuh@gmail.com Kaohsiung Medical University Hospital Division of Nephrology, Department of Internal Medicine Kaohsiung Taiwan *

Co-author 2

Yi-Ting Lin emilyhei@gmail.com Kaohsiung Medical University Hospital Department of Family Medicine Kaohsiung Taiwan -

Co-author 3

Jih-Kai Huang eric86425@gmail.com Kaohsiung Medical University Hospital Department of Emergency Medicine Kaohsiung Taiwan -

Co-author 4

Yun-Shiuan Chuang kinkipag@gmail.com Kaohsiung Medical University Hospital Department of Family Medicine Kaohsiung Taiwan -

Co-author 5

Teng-hui Huang sfestg3329@gmail.com Kaohsiung Medical University Hospital Division of Nephrology, Department of Internal Medicine Kaohsiung Taiwan -

Co-author 6

Ming-Yen Lin mingyenlin3@gmail.com Kaohsiung Medical University Hospital Division of Nephrology, Department of Internal Medicine Kaohsiung Taiwan -

Co-author 7

Mei-Chuan Kuo mechkuster@gmail.com Kaohsiung Medical University Hospital Division of Nephrology, Department of Internal Medicine Kaohsiung Taiwan -

Co-author 8

Yi-Wen Chiu chiuyiwen@gmail.com Kaohsiung Medical University Hospital Division of Nephrology, Department of Internal Medicine Kaohsiung Taiwan -

Co-author 9

Ping-Chi Hsu pchsu@nkust.edu.tw National Kaohsiung University of Science and Technology Department of Safety, Health and Environmental Engineering Kaohsiung Taiwan -

Co-author 10

Samira Salihovic Samira.Salihovic@oru.se Örebro University School of Medical Sciences, Faculty of Medicine and Health Örebro Sweden -

Co-author 11

Shang-Jyh Hwang sjhwang730136@gmail.com Kaohsiung Medical University Hospital Division of Nephrology, Department of Internal Medicine Kaohsiung Taiwan -

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants excreted primarily through the kidneys. Their accumulation in patients with chronic kidney disease (CKD) may accelerate systemic toxicity. However, the interplay between glomerular filtration decline and albuminuria in determining PFAS body burden remains unclear. This study aimed to elucidate how kidney function and albuminuria jointly influence serum PFAS concentrations across CKD stages.

Methods

We recruited 474 CKD patients (Stages 1-5) at Kaohsiung Medical University Hospital between August 2016 and January 2017. Serum concentrations of eight PFAS compounds were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Linear regression and cubic spline models, adjusted for age, sex, diabetes, hypertension, and coronary artery disease, assessed relationships between PFAS levels and kidney function markers. Mediation analysis evaluated UACR's role in the eGFR-PFAS association.

Results

PFAS concentrations increased progressively with CKD severity (PFOA: 1.74 ng/mL in stage 1 to 40.0 ng/mL in stage 4; PFNA: 1.01 ng/mL to 124 ng/mL; P < 0.001), reflecting reduced renal elimination. However, in patients with severe albuminuria (macroalbuminuria), PFAS levels were lower, suggesting loss via albuminuria. Mediation analysis revealed that UACR significantly mediated the association between concentrations of PFHxS, PFOA, PFNA, linear-chain PFOS, total PFOS, and kidney function, accounting for nearly all observed effects. A significant eGFR-UACR interaction indicated that albuminuria modifies PFAS accumulation, with non-linear patterns showing a peak in moderate CKD, followed by a decline in advanced stages.

Conclusion

PFAS accumulation in CKD follows complex, non-linear patterns driven by competing mechanisms: reduced glomerular filtration promotes retention, while severe albuminuria facilitates urinary loss. These findings challenge the assumption of progressive toxin accumulation in kidney disease and highlight the need to incorporate albuminuria status in clinical risk assessment for environmental pollutant exposure in CKD patients.

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