Common Drug Residues Linked to Lower Kidney Function in Older Chinese Adults

A large cross-sectional study of older adults in China has found that several widely used pharmaceuticals and personal care product chemicals, including the antibiotic doxycycline, the diabetes drug metformin, the painkiller acetaminophen, the antibiotic enrofloxacin, and the nicotine breakdown product cotinine, were associated with lower kidney function in people aged 60 and above. The research, published in Environmental Geochemistry and Health, measured 48 pharmaceuticals and personal care products, known as PPCPs, and two metabolites in urine samples from 2,758 community-dwelling adults in Anhui Province between 2022 and 2023.

Kidney function was assessed using the estimated glomerular filtration rate, or eGFR, calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. Urinary concentrations of the compounds were quantified with high-performance liquid chromatography coupled to tandem mass spectrometry, a sensitive analytical technique capable of detecting trace levels of diverse synthetic compounds in biological samples.

Among the nine PPCPs detected in more than half of the participants, five stood out. Doxycycline, enrofloxacin, acetaminophen, metformin, and cotinine were each associated with lower eGFR after the researchers fully adjusted their statistical models and applied the Benjamini-Hochberg procedure to control for false discoveries across multiple comparisons. The associations ranged from a decrease of 3.00 to 0.93 mL/min/1.73 m2 for every tenfold increase in urinary concentration of a given compound.

Not all detected chemicals pointed in the same direction. Tylosin and caffeine were positively associated with eGFR in this population. The contrasting directions of association underscore how chemically and functionally diverse PPCP mixtures are, and why the researchers went beyond single-compound analyses to examine the chemicals as a mixture.

To evaluate the combined effect of the whole mixture, the team used two complementary statistical approaches: weighted quantile sum regression, which builds a single index of the mixture weighted by each component’s contribution, and Bayesian kernel machine regression, which can estimate joint and interactive effects. The weighted quantile sum index was inversely associated with eGFR, and metformin received the largest weight in that index, suggesting it contributed most strongly to the overall negative association.

The study also explored a possible statistical pathway connecting contaminant exposure to kidney health. High-density lipoprotein cholesterol, or HDL-C, showed a positive nonlinear association with eGFR in the study population. Using restricted cubic splines, the investigators examined whether these relationships departed from straight-line dose-response patterns, and the HDL-C association was nonlinear rather than uniform across its range.

Under the assumptions of the mediation model, HDL-C statistically accounted for between 12.21 and 29.30 percent of the associations linking enrofloxacin, metformin, and acetaminophen to lower eGFR, and 13.78 percent of the overall mixture association. The indirect association for cotinine was not statistically significant. In other words, part of the statistical relationship between these common chemicals and reduced kidney function appeared to run through HDL-C levels, although the authors emphasize that this is a statistical decomposition, not proof of a causal mechanism.

The researchers are careful to frame the findings as exploratory. Because the study used a cross-sectional design, measuring exposures and kidney function at the same point in time, it cannot establish whether PPCP exposure preceded differences in kidney function. Reduced kidney function itself can alter the clearance and accumulation of drugs and their metabolites in the body, raising the possibility of reverse causation, in which poorer kidney health leads to higher measured concentrations rather than the other way around.

The authors call for prospective studies that follow participants over time to clarify the temporal relationships between PPCP exposure, lipid metabolism, and kidney function, and to address the possibility of reverse causation directly. Until such longitudinal evidence accumulates, the reported associations should be read as hypothesis-generating signals about a class of widespread environmental contaminants, rather than as established causes of kidney disease in older adults.

Subject of Research: Associations between urinary pharmaceutical and personal care product chemicals, HDL cholesterol, and kidney function in older Chinese adults

Article Title: HDL-C as a mediator of PPCP-related kidney function decline in community-dwelling elderly: a mixture analysis approach

Article References: Zhao, Y., Wang, S., Zhou, L., Xu, Y., Wang, Y., Zhang, S., Gao, Z., Gao, F., Tao, F., & Liu, K. (2026). HDL-C as a mediator of PPCP-related kidney function decline in community-dwelling elderly: a mixture analysis approach. Environmental Geochemistry and Health, 48(16), Article 664. https://doi.org/10.1007/s10653-026-03562-5

Image Credits: AI Generated

DOI: 10.1007/s10653-026-03562-5

Keywords: PPCPs, kidney function, eGFR, HDL cholesterol, metformin, doxycycline, acetaminophen, cotinine, mixture analysis, weighted quantile sum regression, older adults, cross-sectional study