Albuminuria in People Chronically Exposed to Low-Dose Cadmium Is Due to Rising Blood Pressure Levels

Exposure to low-dose environmental pollutant cadmium (Cd) increases the risks of both albuminuria and hypertension by mechanisms which are poorly understood. Here, multiple-regression and mediation analyses were applied to data from 641 Thai subjects of whom 39.8%, 16.5%, 10.8%, and 4.8% had hypertension, albuminuria, diabetes, and chronic kidney disease (CKD), defined as the estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2, respectively. To correct for interindividual differences in urine dilution and surviving nephrons, the excretion rates of Cd (ECd), albumin (Ealb) and β2-microglobulin (Eβ2M) were normalized to creatinine clearance (Ccr) as ECd/Ccr, Ealb/Ccr and Eβ2M/Ccr. Respective risks of having CKD and hypertension rose to 3.52 (95%CI: 1.75, 7.05) and 1.22 (95% CI:1.12, 1.3) per doubling Cd body burden. Respective risk of having albuminuria increased 2.95-fold (p = 0.042), and 4.17-fold (p = 0.020) in subjects who had hypertension plus severe and extremely severe tubular dysfunction, defined according to elevated β2M excretion rates. In multiple regression analysis, Ealb/Ccr increased linearly with both systolic blood pressure (SBP, β = 0.263) and diastolic blood pressure (DBP, β = 0.150), while showing an inverse association with eGFR (β = −0.180). The mediation model analyses inferred that a declining eGFR induced by Cd contributed to 80.6% of SBP increment (p = 0.005), which then fully mediated an elevation of albumin excretion (p < 0.001). The present study provides, for the first time, evidence that causally links Cd-induced eGFR reductions to blood pressure elevations which enhance albumin excretion.