Environmental Lead Exposure and Progression of Chronic Renal Diseases in Patients without Diabetes

BACKGROUND: Previous research suggests that environmental lead exposure correlates with age-related decreases in renal function. METHODS: Two hundred two patients with chronic renal insufficiency (indicated by a serum creatinine level between 1.5 mg per deciliter and 3.9 mg per deciliter) who had a normal total-body lead burden and no history of exposure to lead were observed for 24 months. After the observation period, 64 subjects with an elevated body lead burden were randomly assigned to the chelation control groups. For three months, the patients in the chelation group received lead-chelation therapy with calcium disodium EDTA, and the control group received placebo. During the ensuing 24 months, repeated chelation therapy was administered weekly to 32 patients with high-normal body lead burdens (at least 80 microg but less than 600 microg) unless on repeated testing the body lead burden fell below 60 microg; the other 32 patients served as controls and received weekly placebo infusions for 5 weeks every 6 months. The primary end point was an increase in the serum creatinine level to 1.5 times the base-line value during the observation period. A secondary end point was the change in renal function during the intervention period. RESULTS: The primary end point occurred in 24 patients during the observation period; the serum creatinine levels and body lead burden at base line were the most important risk factors. The glomerular filtration rate improved significantly by the end of the 27-month intervention period in patients receiving chelation therapy: the mean (+/-SD) change in the glomerular filtration rate in the patients in the chelation group was 2.1+/-5.7 ml per minute per 1.73 m2 of body-surface area, as compared with -6.0+/-5.8 ml per minute per 1.73 m2 of body-surface area in the controls (P<0.001). The rate of decline in the glomerular filtration rate in the chelation group was also lower than that in the controls during the 24-month period of repeated chelation therapy or placebo. CONCLUSIONS: Low-level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease. Repeated chelation therapy may improve renal function and slow the progression of renal insufficiency.