Plasma exposome and proteome revealed the role of polycyclic aromatic hydrocarbons in chronic kidney diseases.

Environmental pollutant exposure has been associated with chronic kidney disease (CKD), yet specific chemicals related to renal function variation remain incompletely characterized. We analyzed the plasma exposome using liquid chromatography-mass spectrometry (LC-MS) in 734 biopsy-confirmed CKD patients (452 IgA nephropathy [IgAN] and 282 membranous nephropathy [MN]), quantifying 62 chemical exposure species. Associations between exposures and estimated glomerular filtration rate (eGFR) were assessed using regression models and were further evaluated in an independent external cohort (Shanghai Brain Aging Study, SBAS) of 464 older adults. In addition, clinical remission status was assessed after a median follow-up of one year, and its associations with specific chemicals were subsequently evaluated. Proteomic data were integrated to explore protein features related to the exposure-eGFR association in the MN subgroup. In the discovery CKD cohort, two PAHs, biphenyl and 2,6-dimethylnaphthalene, were associated with lower eGFR after multivariable adjustment, a finding also observed in the external SBAS cohort. Moreover, in the MN subgroup, these two PAHs were also associated with remission status. Proteomic profiling in MN patients identified six proteins (CDH1, CALR, PTGDS, DAG1, PEBP4, and YIPF3) with statistically significant interaction terms for the biphenyl-eGFR association. Combining exposome and proteome analysis, this study identified exploratory associations between PAHs and renal function in CKD patients, and these effects may be related to certain key proteins.