Associations between blood cadmium concentration and kidney function in the U.S. population: Impact of sex, diabetes and hypertension

Abstract

Background: Exposure to cadmium has been associated with nephropathy and implicated in the development of diabetes and hypertension. The role of environmental metal exposure may be an underexplored risk factor for decreased kidney function among people with diabetes and/or hypertension. The objective of this study was to examine the association of blood concentration of cadmium with kidney function parameters and evaluate sex, diabetes, and hypertension as effect modifiers of the association.

Methods: This study used data from 12,577 adult participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2012 cycles. We used multivariable linear and logistic regression models to conduct a cross-sectional analysis of the association between cadmium exposure quartiles and estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), low eGFR (defined as eGFR <60 mL/minute/1.73 m²), and albuminuria (defined as UACR ≥ 30 mg/g). Models were adjusted for confounders and interaction terms were evaluated for cadmium concentration and sex, diabetes, and hypertension. Final models were stratified by sex and indices of existing diabetes and hypertension status.

Results: The mean eGFR was 94.3 mL/minute/1.73 m² (SD 21.5) and the geometric mean of UACR was 7.9 mg/g (95% CI 7.6-8.2 mg/g). Blood cadmium concentration was inversely associated with eGFR and positively associated with UACR. We found significant effect modification of the association of eGFR with cadmium, predominantly for sex and hypertension. The strength of the association between cadmium quartiles and eGFR was more pronounced among females compared to males. Among females with hypertension and diabetes, eGFR was lower on average by 4.9 mL/minute/1.73 m² (95% CI -10.1 to 0.29) in the highest versus lowest cadmium quartile, and in females with hypertension alone, eGFR was lower on average by 5.8 mL/minute/1.73 m² (95% CI -8.2 to -3.3) in the highest versus lowest cadmium quartile. Among those in the highest exposure quartile, higher mean UACR was observed among participants with hypertension compared to those without.

Conclusions: Our results confirm that cadmium exposure is associated with decreased glomerular filtration and increased urine protein excretion, and provide evidence that the magnitude of these associations differ by sex and may vary based on preexisting diabetes and hypertension. Future prospective sex-specific investigations are necessary to address concerns of reverse causality and efforts should be made to reduce smoking and environmental contamination from cadmium to protect human health.

Keywords: Cadmium; Diabetes; Hypertension; Kidney function; NHANES; Sex differences.