Is renal tubular cadmium toxicity clinically relevant?

Exposure to cadmium (Cd) has been associated with the development of hypertension, especially in women, but the mechanism of such an association is not understood. We hypothesize that Cd exposure alters renal production of 20-hydroxyeicosatetraenoic acid (20-HETE), which plays an indispensable role in renal salt balance and blood pressure control.

We examined long-term Cd exposure in relation to urinary 20-HETE excretion levels, tubular dysfunction and blood pressure measures, using data from a population-based, cross-sectional study that included 115 normotensive and 110 hypertensive women, 33-55 years of age, who lived in Cd contamination areas in Thailand.

The mean [standard deviation (SD)] blood Cd level of the study subjects was 3.57 (3.3) µg/L, while the mean (SD) urinary Cd and urinary 20-HETE levels were 0.58 (0.47) µg/g creatinine and 1651 (4793) pg/mL, respectively. Elevated 20-HETE levels were associated with a 90% increase in prevalence odds of hypertension (P = 0.029), four times greater odds of having higher urinary Cd levels (P = 0.030) and a 53% increase in odds of having higher levels of tubular dysfunction (P = 0.049), evident from an increase in urinary excretion of β2-microglobulin. In normotensive subjects, an increase in urinary 20-HETE levels from tertile 1 to tertile 3 was associated with a systolic blood pressure increase of 6 mmHg (95% confidence interval 0.3-12, P = 0.040).

This is the first report that links urinary 20-HETE levels to blood pressure increases in Cd-exposed women, thereby providing a plausible mechanism for associated development of hypertension.