Repeated Lead Chelation Therapy in Maintenance Hemodialysis Patients with High Body Lead Burden---A 3-Year Clinical Trial

Background Several epidemiological studies have demonstrated a positive association between blood lead levels (BLL) and cardiovascular disease mortality in the general population. Previous our works suggest environmental exposure to lead may correlate to progressive renal insufficiency and lead chelation therapy reducing body lead burden (BLB) may improve and slow the progression in patients with chronic kidney disease. However, although patients with chronic dialysis have high BLL due to loss renal function, whether lead influences the health status of these patients remains unknown. In our recent works (Am J Kidney Disease. 2008; 51(1):107-115; Nephrol Dial Transplant. 2010; 25(5):1627-33; and publication on 2011 April; Am J Med, in printed) demonstrated BLL was associated with inflammation, malnutrition, cardiovascular-, infection-, and all-cause mortality in maintenance hemodialysis (MHD) and peritoneal dialysis patients. Moreover, in a recent pilot study with clinical trial, we found 30 study group patients with MHD and high BLB (＞1000 ug) improved their hemoglobin and serum albumin after their BLB were reduced to ＜600 ug by repeated lead chelation therapy for 1 yr. The hemoglobin and serum albumin in the study group after chelation therapy is also higher that those of the control group (n=30), although there were no significant difference of baseline data, BLL, and BLB between the two study groups. Hence, we will arrange the 3-year prospectively study to evaluate whether lead chelation therapy improves the morbidity and mortality in these patients. Methods Four hundred MHD patients receive EDTA mobilization tests to assess their BLB. Two hundred patients with MHD who have no history of exposure to lead and BLB ＞1000 ug by EDTA mobilization tests will be collected during a 6-month period. BLL, BLB, biochemical data, hemoglobin, and high sensitivity C-reactive protein (HsCRP) are assessed at baseline. Subsequently, these patients will be randomly assigned to the study and control groups. For 6-12 months, the 100 study group patients will receive lead-chelation therapy with calcium di-sodium EDTA every other week until the BLB falls below 600 μg, and the 100 control group patients receive every other week placebo. During the ensuing 18-24months, the biochemical data will be regularly followed up every 3 months. BLB and BLL will be measured every 6 months. If BLB of the study group patients increase ＞ 600 μg, the chelation therapy will be performed again until their BLB＜600 μg. The primary end point is mortality and the secondary end point is the morbidity with admission to the hospital during the 18 to 24-month follow up period.

Project ID:PC10007-0387
External Project ID:NSC100-2314-B182A-089