Urinary Metal Levels after Repeated Edetate Disodium Infusions: Preliminary Findings

Abstract

Environmentally acquired lead and cadmium are associated with increased cardiovascular disease risk. In the Trial to Assess Chelation Therapy, up to 40 infusions with edetate disodium over an approximately one-year period lowered the cardiovascular disease risk in patients with a prior myocardial infarction. We assessed whether a reduction in surrogate measures of total body lead and cadmium, post-edetate disodium urine lead and pre-edetate urine cadmium, could be detected after repeated edetate disodium-based infusions compared to the baseline. Fourteen patients with coronary artery disease received multiple open-label edetate disodium infusions. The urine metals pre- and post-edetate infusion, normalized for urine creatinine, were compared to urine levels pre and post final infusion by a paired t-test. Compared with the pre-edetate values, post-edetate urine lead and cadmium increased by 3581% and 802%, respectively, after the first infusion. Compared to baseline, post-edetate lead decreased by 36% (p = 0.0004). A reduction in post-edetate urine lead was observed in 84% of the patients after the final infusion. Pre-edetate lead decreased by 60% (p = 0.003). Pre-edetate lead excretion became undetectable in nearly 40% of patients. This study suggests that edetate disodium-based infusions may decrease the total body burden of lead. However, our data suggest no significant reduction in the body burden of cadmium.

Keywords: atherosclerosis; cadmium; chelation; lead; vascular disease.

Figure 1

Within-person change comparing pre versus post edetate chelation urinary lead concentrations (µg/g of creatinine). All values are controlled for creatinine concentration. Results are presented separately for the first (baseline) and last (final) infusion visits. Each black dot (jittered) represents an individual patient measurement. Gray lines connect measurements from individual patients and indicate a within-person change in urinary lead concentrations. Boxplot upper, middle, and lower hinges correspond to the 25th, 50th, and 75th percentiles, respectively. The left panel compares the within-person change in the urinary lead concentrations in urine samples collected at the first (baseline) visit, comparing pre versus post edetate chelation. The left panel compares the within-person change in urinary lead concentrations in urine samples collected at the last (final) visit, comparing pre versus post edetate chelation. Urinary lead concentrations are plotted on a log scale. The blue horizontal bars represent the median values.

Figure 2

Effect of chelation therapy on patient urinary lead concentrations (µg/g of creatinine). All values are controlled for creatinine concentration. Each dot represents the within-person change in urinary lead concentrations (µg/g of creatinine) comparing urine collected at the last (final) infusion minus urine collected at the first (baseline) infusion for an individual patient. The left panel compares the within-person change in the urinary lead concentrations (µg/g of creatinine) for urine samples collected pre edetate chelation. The right panel compares the within-person change in urinary lead concentrations (µg/g of creatinine) for urine samples collected post edetate chelation. Boxplot upper, middle, and lower hinges correspond to the 25th, 50th, and 75th percentiles, respectively. The red dashed line indicates zero (no change).

Figure 3

Within-person change in urinary lead concentrations (µg/g of creatinine) comparing the first and last infusion visits. Results are presented separately for urinary lead concentrations measured pre versus post edetate chelation. All values are controlled for creatinine concentration. Each black dot (jittered) represents an individual patient measurement. Gray lines connect measurements from individual patients and indicate a within-person change in the urinary lead concentrations. Boxplot upper, middle, and lower hinges correspond to the 25th, 50th, and 75th percentiles, respectively. The left panel compares the within-person change in the urinary lead concentrations in urine samples collected pre edetate chelation, comparing the first (baseline) and last infusion visits. The right panel compares the within-person change in the urinary lead concentrations in urine samples collected post edetate chelation, comparing the first (baseline) and last infusion visits. Orange horizontal bars represent the median values.