Urinary β2-Microglobulin Predicts the Risk of Hypertension in Populations Chronically Exposed to Environmental Cadmium

Chronic exposure to the pollutant cadmium (Cd) is inevitable for most people because it is present in nearly all food types. Concerningly, the risk of developing hypertension has been linked to dietary Cd exposure lower than 58 µg/day for a 70 kg person. The mechanisms involved are, however, unclear. Since the kidneys play an indispensable role in long-term blood pressure regulation, and they are also the main site of Cd accumulation and toxicity, a retrospective analysis was conducted to examine if kidney damage and malfunction, reflected by urinary β₂-microglobulin excretion (E_β2M), and the estimated glomerular filtration rate (eGFR), are related to Cd excretion (E_Cd) and blood pressure variation. Data were obtained from 689 Thai Nationals without diabetes or occupational exposure to Cd, of which 32.4% had hypertension and 7.3% had β₂-microglobulinuria, defined as an increase in the β₂M excretion rate ≥ 300 µg/g creatinine. Respective prevalence odds ratio (POR) and 95% confidence interval (CI) values for β₂-microglobulinuria and hypertension were 10.7 (1.36-83.4), <i>p</i> = 0.024 and 2.79 (1.60-4.87) <i>p</i> < 0.001, comparing the top quartile of E_Cd with the bottom quartile. Only in subjects with eGFR below 90 mL/min/1.73 m² did systolic blood pressure (SBP) and diastolic blood pressure (DBP) both increase linearly with E_β2M (respective β = 0.182 and 0.192 for SBP and DBP) after adjustment for age, body mass index, gender, and smoking. The present study confirms the significant impact of Cd on the risk of having hypertension, following GFR loss induced by Cd. A simple mediation model analysis for cause-effect inference has provided, for the first time, evidence that may link rising SBP and DBP in Cd-exposed people to a novel role of β₂M as a predictor of blood pressure variability.