Toenail metal concentrations and kidney health among young people at risk of chronic kidney disease of uncertain etiology.

Abstract

Background: Metal exposure is a hypothesized risk factor for chronic kidney disease of uncertain etiology, an ongoing epidemic in Central America, yet metal biomonitoring data in this region are scant.

Methods: We measured metal toenail concentrations using inductively coupled plasma mass spectrometry and calculated estimated glomerular filtration rate (eGFR) in a cohort of Nicaraguans 14-31 years (n = 297; 49% female; data collected in 2023). We used multivariable linear and ordinal regression and Bayesian kernel machine regression to examine individual element and mixture associations of arsenic, cadmium, mercury, nickel, lead, and uranium with eGFR.

Results: The middle tertile of nickel was associated with -6.92 ml/min/1.73 m² reduction in eGFR (95% confidence intervals [CI] = -10.7, -3.12) compared to the lowest tertile, suggesting a "U-shaped" association. The highest tertile of arsenic was associated with -4.25 ml/min/1.73 m² eGFR reduction (95% CI = -8.42, -0.07) compared to the lowest tertile. Associations between other metals and eGFR were not detected. We observed no evidence of higher-order interactions or joint effects of the metal mixture on eGFR.

Conclusions: In this sample of young people in a high-chronic kidney disease of uncertain etiology-risk region, nickel and arsenic were independently associated with reduced eGFR, but other metals and their mixture were not. This finding supports targeted metals biomonitoring and source investigation.