Association of non-methane volatile organic compound emission burden with chronic kidney disease: integrated epidemiological, transcriptomic and in vitro analyses
4 affiliations
- 1Department of Endocrinology and Metabolism, Xi’an No.3 Hospital, Affiliated Hospital of Northwest University, Xi’an, Shaanxi Province, China
- 2Department of Faculty of Life Science and Medicine, Northwest University, Xi’an, Shaanxi Province, China
- 3Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
- 4Xi’an Key Laboratory of Metabolic Disease Imaging, Xi’an No.3 Hospital, Affiliated Hospital of Northwest University, Xi’an, Shaanxi Province, China
Abstract
Background: Environmental exposure to non-methane volatile organic compounds (NMVOCs) may contribute to chronic kidney disease (CKD), but the underlying molecular pathways remain unclear. We integrated epidemiological, transcriptomic, single-cell, and experimental analyses to identify candidate mechanisms linking NMVOCs to kidney injury.
Methods: Province-level NMVOC emission burden was linked to residential province for 3,472 participants in the China Health and Retirement Longitudinal Study (CHARLS). CKD was defined as an eGFR <60 mL/min/1.73 m2. Associations were evaluated using multivariable logistic regression. Putative NMVOC-CKD targets, kidney transcriptomic datasets, 113 machine-learning models, and SHapley Additive exPlanations (SHAP) were used to prioritize biomarkers. Single-cell transcriptomics, cell-communication analysis, virtual knockout, and hydroquinone-treated cell experiments were used to investigate candidate pathways.
Results: Among 3,472 participants, 417 had CKD. In the fully adjusted model, higher province-level NMVOC emission burden was associated with greater odds of prevalent CKD (OR = 1.05). The best transcriptomic classifier achieved areas under the curve of 0.964 and 0.836 in the training and validation sets. Integrated analyses prioritized SLC9A3 and localized its expression to proximal tubular cells. Single-cell analysis predicted SPP1-ITGAV/ITGB1 signaling between proximal tubular cells and fibroblasts. In a benzene-metabolite model, hydroquinone increased tubular SLC9A3 and SPP1 expression; conditioned medium increased fibroblast ITGB1 and α-smooth muscle actin expression and migration.
Conclusions: Province-level NMVOC emission burden was associated with CKD. The findings nominate proximal-tubule SLC9A3/SPP1-integrin signaling as a candidate link between NMVOC emission burden and fibroblast activation, warranting validation through individual-level exposure assessment and targeted perturbation studies.
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BibTeX
@article{yan2026association,
title = {{Association of non-methane volatile organic compound emission burden with chronic kidney disease: integrated epidemiological, transcriptomic and in vitro analyses}},
author = {Chunyu Yan and Yifan Zhao and Guang Chen and Jin Wu and Li Zhang and Ting Wang and Yizhi He and Linxi Zhang and Ping Liu},
journal = {Renal Failure},
year = {2026},
month = oct,
doi = {10.1080/0886022x.2026.2751342},
url = {https://doi.org/10.1080/0886022x.2026.2751342},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Association of non-methane volatile organic compound emission burden with chronic kidney disease: integrated epidemiological, transcriptomic and in vitro analyses
AU - Chunyu Yan
AU - Yifan Zhao
AU - Guang Chen
AU - Jin Wu
AU - Li Zhang
AU - Ting Wang
AU - Yizhi He
AU - Linxi Zhang
AU - Ping Liu
PY - 2026
DA - 2026/10/30
JO - Renal Failure
DO - 10.1080/0886022x.2026.2751342
UR - https://doi.org/10.1080/0886022x.2026.2751342
AB - Background: Environmental exposure to non-methane volatile organic compounds (NMVOCs) may contribute to chronic kidney disease (CKD), but the underlying molecular pathways remain unclear. We integrated epidemiological, transcriptomic, single-cell, and experimental analyses to identify candidate mechanisms linking NMVOCs to kidney injury. Methods: Province-level NMVOC emission burden was linked to residential province for 3,472 participants in the China Health and Retirement Longitudinal Study (CHARLS). CKD was defined as an eGFR <60 mL/min/1.73 m2. Associations were evaluated using multivariable logistic regression. Putative NMVOC-CKD targets, kidney transcriptomic datasets, 113 machine-learning models, and SHapley Additive exPlanations (SHAP) were used to prioritize biomarkers. Single-cell transcriptomics, cell-communication analysis, virtual knockout, and hydroquinone-treated cell experiments were used to investigate candidate pathways. Results: Among 3,472 participants, 417 had CKD. In the fully adjusted model, higher province-level NMVOC emission burden was associated with greater odds of prevalent CKD (OR = 1.05). The best transcriptomic classifier achieved areas under the curve of 0.964 and 0.836 in the training and validation sets. Integrated analyses prioritized SLC9A3 and localized its expression to proximal tubular cells. Single-cell analysis predicted SPP1-ITGAV/ITGB1 signaling between proximal tubular cells and fibroblasts. In a benzene-metabolite model, hydroquinone increased tubular SLC9A3 and SPP1 expression; conditioned medium increased fibroblast ITGB1 and α-smooth muscle actin expression and migration. Conclusions: Province-level NMVOC emission burden was associated with CKD. The findings nominate proximal-tubule SLC9A3/SPP1-integrin signaling as a candidate link between NMVOC emission burden and fibroblast activation, warranting validation through individual-level exposure assessment and targeted perturbation studies.
SN - 0886-022X
SN - 1525-6049
ER -