Effect of Chelation Therapy on Progressive Diabetic Nephropathy in Patients With Type 2 Diabetes and High-Normal Body Lead Burdens

Division of Clinical Toxicology, Department of Nephrology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Chang Gung University School of Medicine, Taipei, Taiwan, Republic of China.
American Journal of Kidney Diseases (Impact Factor: 5.9). 06/2012; 60(4):530-8. DOI: 10.1053/j.ajkd.2012.04.028
Source: PubMed


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.
A 12-month run-in phase, then a randomized single-blind study with a 27-month intervention.
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.
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.
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.
Body lead burdens were assessed by EDTA mobilization tests and eGFR was calculated using the equation for Chinese patients with type 2 diabetes.
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.
Small sample size, not double blind.
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.

1 Follower
38 Reads
  • Source
    • "Multivariate Cox analysis indicated each 100-μg increase of BLB could lead to a 100% increase in the risk of achieving primary outcome. Consistent with this result, EDTA chelation therapy has shown benefits in retarding progressive diabetic nephropathy in type II diabetic patients with high-normal BLB [14, 26]. Hence, environmental exposure to lead may accelerate progressive diabetic nephropathy in these patients, and it is reasonable to suggest chelation therapy for patients with high-normal BLB, who accounted for 70% (62/89) of the current study patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600 μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80 μ g) and low-normal BLB (<80 μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100 μ g increment in BLB and each 10 μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.
    02/2013; 2013:742545. DOI:10.1155/2013/742545
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study evaluates combination therapy with a chelating agent, MiADMSA and a Na(+) ionophore, monensin against sub-chronic lead toxicity in rats. Animals were exposed to 0.1% lead in drinking water for 16weeks and then treated with either MiADMSA at 50mg/kg body weight, or monensin at 10mg/kg, or both in combination for a period of 5days was administered. Biomarkers indicative of oxidative stress like ROS, GSH, GSSG and TBARS demonstrated lead-induced toxic manifestations in blood, kidney and brain. Antioxidants like SOD, catalase and glutathione peroxidase along with specific lead biomarker, blood ALAD were also severely depleted in lead intoxicated animals. Serum parameters and histopathological findings supported the said results. MiADMSA treatment during both mono- and combination therapy with monensin, restored the antioxidant status and recovered biochemical and haematological variables due to lead. However, monensin alone was not found to be effective in the given scenario. Interestingly, combination therapy in its ability to revert lead-induced overall systemic toxicity was only found at par with the MiADMSA monotherapy except for its chelation potential. Monensin given in combination with MiADMSA potentiated its lead chelation ability especially from brain, along with maintaining the normal copper concentrations in the organ unlike MiADMSA monotherapy.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 09/2012; 50(12):4449-4460. DOI:10.1016/j.fct.2012.08.059 · 2.90 Impact Factor
  • American Journal of Kidney Diseases 10/2012; 60(4):503-6. DOI:10.1053/j.ajkd.2012.07.006 · 5.90 Impact Factor
Show more