EDTA Chelation Therapy May Prevent Progression of Renal Disease
Laurie Barclay, MD
January 22, 2003
Strategies for Planning the Optimal Dialysis Access for an Individual Patient Differential Scaling of Glomerular Filtration Rate and Ingested Metabolic Burden Incident ESRD Among Participants in a Lead Surveillance Program
Jan. 22, 2003 — Ethylenedinitrilo tetraacetic acid (EDTA) chelation therapy presumably reduces the progression of renal disease in patients with high normal lead levels and without diabetes, according to the results of a randomized trial reported in the Jan. 23 issue of the New England Journal of Medicine.
“Low-level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease,” write Ja-Liang Lin, MD, and colleagues from Chang Gung University in Taipei, Taiwan. “Repeated chelation therapy may improve renal function and slow the progression of renal insufficiency.”
For 24 months, the investigators observed 202 patients with chronic renal insufficiency (serum creatinine 1.5 – 3.9 mg/dL), normal total-body lead burden, and no history of exposure to lead. After this observation period, 64 subjects with an elevated body lead burden were randomized to lead-chelation therapy with calcium disodium EDTA, or to placebo, for three months. For the next 24 months, 32 patients with high-normal body lead burdens (80 – 599 μg) received weekly chelation therapy; this was discontinued if body lead burden fell below 60 μg. The remaining 32 patients received weekly placebo infusions for five weeks every six months.
During the observation period, 24 patients reached the primary end point of increased serum creatinine to 1.5 times baseline value. Predictors of reaching this endpoint were serum creatinine level and body lead burden at baseline.
After the 27-month intervention period, glomerular filtration rate (GFR) improved significantly in the chelation group but declined in the controls (change in GFR, 2.1 5.7 mL/min/1.73 m 2 body-surface area vs. -6.0 5.8 mL/min/1.73 m 2; P < .001). During the 24-month period of repeated chelation therapy or placebo, the rate of decline in GFR was also lower in the chelation group than in the controls.
In an accompanying editorial, Philip A. Marsden, MD, from St. Michael’s Hospital at the University of Toronto in Canada, commends the investigators, but wonders if the findings are generalizable to Europe or North America. Environmental lead contamination, genetic susceptibility to lead accumulation, and lack of treatment with angiotensin-converting enzyme inhibitors in the absence of hypertension could all be different in the Taiwanese population. Another caveat is that EDTA therapy can exacerbate cognitive dysfunction and other adverse effects of lead exposure.
Finally, he notes that EDTA “has protean biochemical and cellular effects both in vitro and in vivo…. Some may rightfully argue that the results do not demonstrate that lead-chelation therapy improves short-term renal function in humans. Rather, they show that EDTA-chelation therapy does.”