Effect of chelation therapy on progressive diabetic nephropathy in patients with type 2 diabetes and high-normal body lead burdens.

BACKGROUND: A previous study in type 2 diabetic patients with high-normal body lead burdens showed that EDTA chelation therapy for 3 months slows progressive diabetic nephropathy during a 12-month follow-up. The effect of a longer course of therapy on kidney function decrease over a longer follow-up is not known. STUDY DESIGN: A 12-month run-in phase, then a randomized single-blind study with a 27-month intervention. SETTING & PARTICIPANTS: University medical center; 50 patients (serum creatinine, 1.5-3.9 mg/dL) with high-normal body lead burden (≥80-<600 µg) were randomly assigned to the treatment and control groups. INTERVENTION: The treatment group received weekly chelation therapy for 3 months to reduce their body lead burden to <60 µg and then as needed for 24 months to maintain this level. The control group received placebo for 3 months and then weekly for 5 weeks at 6-month intervals for 24 months. OUTCOMES: The primary end point was change in estimated glomerular filtration rate (eGFR) over time. A secondary end point was a 2-fold increase in baseline serum creatinine level or the requirement for renal replacement therapy. MEASUREMENTS: Body lead burdens were assessed by EDTA mobilization tests and eGFR was calculated using the equation for Chinese patients with type 2 diabetes. RESULTS: Mean baseline eGFRs in the treatment and control groups were similar. After 3 months of chelation therapy, the change in eGFR in the treatment group (+1.0 ± 4.8 mL/min/1.73 m(2)) differed significantly from that in the control group (-1.5 ± 4.8 mL/min/1.73 m(2); P = 0.04). In the subsequent 24-month intervention, the yearly rate of decrease in eGFR (5.6 ± 5.0 mL/min/1.73 m(2) per year) in the treatment group was slower than that (9.2 ± 3.6 mL/min/1.73 m(2) per year; P = 0.04) in the control group. 17 (68%) control-group patients and 9 (36%) treatment-group patients achieved the secondary end point. LIMITATIONS: Small sample size, not double blind. CONCLUSIONS: A 27-month course of EDTA chelation therapy retards the progression of diabetic nephropathy in type 2 diabetic patients with high-normal body lead burdens.

Long-term outcome of repeated lead chelation therapy in progressive non-diabetic chronic kidney diseases.

BACKGROUND: Previous research suggest that repeated lead-chelation therapy decelerates progression of renal insufficiency in non-diabetic (non-DM) patients with high-normal body lead burden (BLB). Study findings are limited by relatively short-term follow-up and small sample size. METHODS: A total of 116 non-DM patients with chronic kidney diseases (serum creatinine level of 1.5-3.9 mg/dl), high-normal BLB (>60 microg and <600 microg) and no lead exposure history were randomly assigned to a chelation or control group in this 4-year clinical trial. For 3 months, the 58 chelation group patients received initial lead-chelation therapy with calcium disodium EDTA, and the 58 control group patients received placebos. During the ensuing 48 months, repeated chelation therapy was administered weekly to chelation group patients unless, on repeated testing, BLB was <60 microg; the control group patients received weekly placebo infusions for 5 weeks at 6-month intervals. RESULTS: Mean change in the glomerular filtration rate (GFR) in the chelation group was -1.8 +/- 8.8 ml/min/1.73 m(2), as compared with -12.7 +/- 8.4 ml/min/1.73 m(2) in the control group (P <0.0001) at study end. Chelation group rates of decline in the GFR was lower than that in the control group, although they had similar decline rates before chelation. At study end, 18 patients, including 15 control group patients, had elevated serum creatinine levels to two times the baseline values. Both Cox and Kaplan-Meier analysis demonstrated repeated chelation therapy was the important determining factor of progression of renal insufficiency. CONCLUSIONS: Repeated chelation therapies can, over a four-year period, slow progression of renal insufficiency in non-DM patients with high-normal BLB.

Low-level environmental exposure to lead and progressive chronic kidney diseases.

PURPOSE: To determine whether low-normal body lead burden (BLB) accelerates progressive renal insufficiency in nondiabetic patients with chronic kidney diseases (CKD). METHODS: One hundred eight CKD patients (serum creatinine between 1.5 and 2.9 mg/dL) with low-normal BLB (<80 microg) and no lead exposure history were observed for 24 months. Following the observation, 32 patients with low-normal BLB (> or =20 microg and <80 microg) were randomly assigned to chelation and control groups. The chelation group patients were given edetate calcium disodium (EDTA) chelation therapy for 3 months and repeated chelation therapy during the following 24 months to maintain their BLB below 20 mug, while the control group patients underwent placebo therapy. The primary endpoint was an increased serum creatinine level to 1.25 times the baseline value. The secondary endpoint was temporal changes in renal function. RESULTS: The primary endpoint occurred in 14 patients in the observation period. Baseline BLB was the important risk factor in determining progressive renal insufficiency. The mean glomerular filtration rate (GFR) change in the chelation group patients was 6.6+/-10.7 mL/min/1.73m(2), compared with -4.6+/-4.3 mL/min/1.73 m2 in control group patients (P <.001) at the end of the intervention period. The mean decrease in GFR per year of chelation group patients was lower than that of control group patients during the repeated chelation period. CONCLUSION: Environmental exposure to lead, even at low level, may accelerate progressive renal insufficiency of nondiabetic patients with CKD.

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.