A Comparative Study on the Paradoxical Relationship Between Heavy Metal Exposure and Kidney Function Original paper

What was studied?

This study examined the paradoxical relationship between heavy metal exposure and kidney function, focusing on a “heavy metal exposure and kidney function” integrated assessment across the Korean population and environmentally vulnerable regions. Using data from the Fourth Korean National Environmental Health Survey (KoNEHS) and the FROM cohort, the authors evaluated whether exposure to lead (Pb), mercury (Hg), and cadmium (Cd) demonstrated consistent or divergent associations with estimated glomerular filtration rate (eGFR). Notably, the paper explored why residents in vulnerable areas—who carried significantly higher exposures—exhibited an unexpected pattern where elevated heavy metals appeared to correlate with preserved or even increased eGFR. Integrated heavy metal concentration (ΣHM) served as the primary exposure metric, and comprehensive statistical analyses assessed correlations and odds ratios for eGFR decline.

Who was studied?

Two major populations were analyzed. The general population consisted of 2,984 adults aged ≥19 years from the nationally representative KoNEHS dataset (2018–2020). In contrast, the environmentally vulnerable group comprised 1,157 adults living within 10 km of 13 predefined contaminated areas, as part of the FROM study (2021–2023). These individuals had prolonged exposure to industrial emissions, abandoned mines, smelters, and coal-fired power plant byproducts. Participants underwent detailed biomonitoring of blood Pb and Hg, urinary Cd, and serum creatinine, with broad age representation but a high proportion of older adults in vulnerable regions. The vulnerable cohort, therefore, reflected both chronic exposure and age-related renal vulnerability—two factors likely central to the paradoxical findings.

Most important findings

The study confirmed substantially higher heavy metal levels in vulnerable areas—blood Pb nearly twice that of the general population, urinary Cd more than doubled, and Hg elevated in multiple regions. However, associations with renal function diverged sharply. In the general population, higher ΣHM and particularly urinary Cd were linked to declining eGFR, aligning with known nephrotoxic pathways involving proximal tubular dysfunction, oxidative stress, and impaired filtration. In contrast, vulnerable-area residents displayed positive correlations between ΣHM and eGFR, suggesting altered excretion dynamics, long-term adaptive responses, or shifts in steady-state metal distribution. Logistic models revealed that urinary Cd increased the odds of eGFR <60 ml min 1.73 m² by 19.9% in the general population, whereas same exposure reduced odds 23.3% vulnerable groups. this paradox may reflect renal cd excretion due to preexisting microstructural decline, leading higher circulating metals but preserved filtration metrics at certain thresholds. < p>

Key implications

This comparative analysis highlights that heavy metal exposure does not uniformly affect kidney function across populations. Chronic exposure, aging kidneys, and reduced urinary excretion likely alter biomarker behavior, producing misleading “protective” associations in heavily exposed communities. Clinicians must therefore interpret urinary Cd and blood metal levels cautiously, especially in older adults or those with long-term exposure histories. The findings underscore the need for early detection thresholds, integration of toxicokinetic biomarkers, and microbiome-focused research, given that heavy metals modulate gut microbial composition, impair detoxification pathways, and reshape microbially mediated metal handling. Identifying microbial signatures of metal burden—such as reduced Lactobacillus and Bifidobacterium, or enrichment of metal-resistant genera—could enhance screening and risk stratification.

Citation

Rho JH, Lee S, Kwon JY, Hong YS. A Comparative Study on the Paradoxical Relationship Between Heavy Metal Exposure and Kidney Function. Diagnostics. 2025;15:86. doi:10.3390/diagnostics15010086