Association between blood and urine manganese levels and cardiorenal outcomes in adolescents: NHANES 2013-2018

Abstract

BACKGROUND AND AIM: Manganese (Mn), an essential mineral, is naturally present in many foods; however, deficiency or excess exposure may have potential adverse health effects. The kidneys are a major organ of Mn site-specific toxicity because of their unique role in filtration, metabolism, and excretion of xenobiotics. Limited evidence has identified the effects of Mn on renal or cardiovascular dysfunction, especially in adolescents. We hypothesized that Mn concentrations were associated with poorer cardiorenal outcomes such as estimated glomerular filtration rate (eGFR), blood pressure (BP), and blood urea nitrogen (BUN). METHODS: We conducted a cross-sectional analysis of 2,002 US adolescents aged 10-19 years participating in NHANES cycles 2013-2014, 2015-2016, and 2017-2018. Blood Mn concentrations were measured using inductively coupled plasma mass spectrometry. Systolic (SBP) and diastolic (DBP) BP was calculated as the average of available readings. eGFR was calculated from serum creatinine using the Bedside Schwartz equation. We performed multiple linear regression, adjusted for race, age, gender, BMI, race/ethnicity, and poverty income ratio. RESULTS:The average age of participants was 15.4 years. Median blood Mn concentration was 10.4 ug/L (IQR: 8.4, 13.1 ug/L). We observed that a log10-unit increase in blood Mn ug/L was marginally associated with a 6.41 mL/min higher eGFR (95% CI: -0.32, 13.14). We observed null relationships for BP and BUN outcomes. There were no significant differences when stratified by sex. CONCLUSIONS:Our findings suggest that Mn exposure may have implications for kidney health reflecting potential hyperfiltration. Additional analyses will examine non-linear relationships. We cautiously interpret these findings, as reverse causality cannot be ruled out. These findings warrant further investigation in longitudinal studies. KEYWORDS: Environmental Epidemiology, Heavy Metals, Cardiovascular Disease, Outcomes