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Primary Submission Category: Biomarkers or biological pathways
Cross-Sectional Associations between Essential and Non-Essential Metals and Kidney Function: A Population-Based Analysis in Midlife Adults
Authors: Rob Warren, Shannon Sullivan, Jesse Seegmiler, Weihua Guan, Amy Karger, Eric Grodsky, Chandra Muller, Bharat Thyagarajan,
Presenting Author: Rob Warren*
Low-level metal exposure is a risk factor for renal decline, yet the roles of essential versus non-essential metals are poorly understood. Essential metals (cobalt [Co], copper [Cu], manganese [Mn], selenium [Se], zinc [Zn]) are physiological requirements but can be toxic at high concentrations or deficient at low; non-essential metals (arsenic [As], cadmium [Cd], lead [Pb]) lack biological utility and are toxic even at low concentrations. We investigated associations between these metals and kidney function (estimated glomerular filtration rate, eGFR) in the nationally representative High School & Beyond 1980 cohort. In 2021 (mean age~59), a subset (n~4,140) provided blood samples analyzed for eight metals using inductively coupled plasma mass spectrometry. eGFR (mL/min/1.73 m2) was calculated using the 2021 CKD-EPI Creatinine-cystatin-C equation. Survey-weighted linear regression, adjusted for age, sex, race/ethnicity, BMI, hypertension, diabetes, education, smoking, and red blood cell count, estimated cross-sectional differences in mean eGFR across tertiles of blood metal concentrations. Tertile analyses identified four metals associated with eGFR. Compared to the lowest tertile (T1), the highest tertile (T3) of Mn (β=−2.76, 95%CI=-4.81, -0.71) and Pb (β=−2.76, 95%CI=-4.87, -0.65) were associated with reduced eGFR. Conversely, T3 of Se (β=2.59, 95%CI=0.38, 4.49) and As (β=2.59, 95%CI=0.52, 4.65) were associated with higher eGFR. No associations were observed for Co, Cu, Zn, or Cd. Survey-weighted metal concentrations were comparable to U.S. adult levels in NHANES 2017-2018. Both essential (Mn) and non-essential (Pb) metals were associated with lower kidney function at higher exposure levels. Conversely, Se’s positive association suggests a potential nephroprotective role, whereas the As finding may reflect dietary sources rather than reduced toxicity. These findings highlight the need to balance essential nutrient status against environmental toxicant exposures.