Lead Chelation Therapy Research Articles

ANALYSIS OF HISTORICAL MEDICAL RECORDS OF CALIFORNIA CONDORS ( GYMNOGYPS CALIFORNIANUS) ADMITTED FOR LEAD EXPOSURE TO THE LOS ANGELES ZOO AND BOTANICAL GARDENS BETWEEN 1997 AND 2012: A CASE SERIES STUDY.

Lead toxicosis remains the primary cause of death in wild populations of California condors ( Gymnogyps californianus). Many condors require medical intervention with lead chelation therapy, among other conservation measures, to survive in the wild. An analysis of historical medical records of California condors admitted for lead exposure to the Los Angeles Zoo and Botanical Gardens (LA Zoo) between 1997 and 2012 was performed to investigate clinical presentation, radiographic findings, and treatment along with the potential impact of these factors on recovery and successful release back into the wild. Of 100 individual condors presented to the LA Zoo for suspected lead toxicosis during this period, 84 condors had records for initial laboratory blood lead levels. For these 84 condors (40 [47.6%] females and 44 [52.4%] males), 277 initial laboratory blood lead levels in total were recorded because of repeated admissions. Thirty-two (38%) condors were admitted once to the zoo and 62% were admitted two or more times. Clinical signs were not observed in 87.5% of the condors admitted with median blood lead concentrations of 26 μg/dl. Of the radiographs taken on initial presentation, 65% did not show evidence of gastrointestinal metallic foreign bodies. Various treatments protocols with edetatum calcium disodium, dimercaptosuccinic acid, and lactated Ringer's solution were documented in the medical records. Of the 277 admissions, 154 admissions had a recorded outcome posttreatment of which 140 (91%) admissions were released back to the wild. This study contributes to a better understanding of how intervention and therapeutic approaches have been essential for the recovery, release, and sustainability of these birds as a wild population. Consistency in data collection of California condors admitted for diagnosis and treatment of lead toxicosis is needed to better assess the impacts of medical interventions.

Reversing the adverse biochemical effects in lead-intoxicated rats by N,N`- bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine

N,N`-Bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine (HTPL) is a novel newly synthesized compound intended to be used for the chelation of lead in intoxicated animals. Subchronic lead intoxication experiments were carried out on Wistar male rats; these rats were intoxicated with lead and then treated with HTPL. Results were compared with those obtained with known compounds used for lead chelation therapy, such as disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA), using different routes of administration. Biological samples of whole blood and urine were collected and analyzed for urinary proporphyrins, δ-aminolevulinic acid dehydratase, and zinc protoporphyrin. Results revealed that HTPL can remarkably reverse the toxic effects of lead intoxication at biochemical levels. Additionally, results showed that this agent is as good or even more potent than calcium disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA) in reversing the toxic effect of lead. More importantly, HTPL was found effective when administrated intraperitoneally and orally.

Is lead chelation therapy effective for chronic kidney disease? A meta‐analysis

The heavy metal lead (Pb) is a major environmental and occupational hazard. Epidemiological studies have demonstrated a strong association between lead exposure and the presence of chronic kidney injury. Some studies have suggested that chelation therapy with calcium disodium ethylenediaminetetraacetic acid (calcium disodium EDTA) might help decrease the progression of chronic kidney disease among patients with measurable body lead burdens. However, calcium disodium EDTA chelation in lead exposure is controversial due to the potential for adverse effects such as acute tubular necrosis. Therefore, we investigated the available randomized controlled trials assessing the renoprotective effects of calcium disodium EDTA chelation therapy. Our meta-analysis shows that calcium disodium EDTA chelation therapy can effectively delay the progression of chronic kidney disease in patients with measurable body lead burdens reflected by increasing the levels of estimated glomerular filtration rate (eGFR) and creatinine clearance rate (Ccr). There appears to be no conclusive evidence that calcium disodium EDTA can decrease proteinuria.

Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney disease

A 60-year-old man with a history of diabetes and hypertension was referred to a nephrology clinic for investigation of his elevated serum creatinine level. Physical examination; laboratory investigations, including measurement of whole-blood lead level, body lead burden and urine albumin:creatinine ratio; history of lead exposure and use of herbal medical products; and renal ultrasonography. Stage 3 chronic kidney disease that was probably worsened by consumption of lead in the form of an Ayurvedic herbal remedy. Cessation of the herbal product, followed by lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid. The patient's whole-body lead burden and blood lead level decreased to acceptable levels and his serum creatinine value was within the normal range at final follow-up.

Lead chelation therapy retards the decline of renal function in patients with chronic kidney disease

Lead chelation therapy retards the decline of renal function in patients with chronic kidney disease

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

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. 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. 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. Repeated chelation therapies can, over a four-year period, slow progression of renal insufficiency in non-DM patients with high-normal BLB.

Environmental exposure to lead and progressive diabetic nephropathy in patients with type II diabetes

Studies indicate that environmental exposure to lead is associated with reduced renal function. Whether lead affects progressive diabetic nephropathy is unclear. Eighty-seven patients with type II diabetes and diabetic nephropathy (serum creatinine of 1.5-3.9 mg/dl) with normal body lead burden and no lead exposure history were observed over a 12-month period. Thirty subjects with high normal body lead burdens (80-600 microg) were randomly assigned to a chelation and control group. For 3 months, the 15 chelation-group patients underwent lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly until body lead burden fell <60 microg, and the 15 control group subjects received a weekly placebo. During the following 12 months, renal function was regularly assessed at 3-month intervals. The primary outcome was an elevation of serum creatinine to 1.5 times baseline value during the observation period. A secondary outcome was temporal changes in renal function following chelation therapy. Twenty-six patients achieved the primary outcome. Basal blood lead levels and body lead burden were the most important risk factors in predicting progressive diabetic nephropathy. Following chelation, the rates of decline in glomerular filtration rates in the chelation group and the control group, respectively, were 5.0+/-5.7 ml and 11.8+/-7.0 ml/min/year/1.73 m(2) of body surface area (P=0.0084) during follow-up, although both groups had similar rates of progression of renal function during the 12-month observation period. We concluded that low-level environmental lead exposure accelerates progressive diabetic nephropathy and lead-chelation therapy can decrease its rate of progression.

Lead-Chelation Therapy -- A Treatment for Chronic Renal Disease?

Chronic renal insufficiency is associated with an increased body lead burden. However, it is unclear whether long-term, low-level, environmental lead

Environmental lead exposure and urate excretion in the general population

Purpose Chronic occupational exposure to lead is related to low urate excretion and a high incidence of gout in lead workers. However, whether chronic low-level environmental lead exposure influences urate excretion in the general population remains unknown. Subjects and methods We studied 111 healthy subjects with normal renal function (serum creatinine level ≤1.4 mg/dL) and no previous lead exposure or systemic diseases. All subjects had their blood lead levels measured, received ethylenediaminetetraacetic acid mobilization tests to assess their body lead burdens, and were investigated for renal function and urate excretion to assess the relation between lead and urate excretion. We studied urate excretion before and after lead chelation therapy in 24 subjects with high-normal body lead burden (>78 mg and <600 mg). Results Healthy subjects with gout (n = 27) manifested a higher body lead burden (84 ± 42 mg vs. 45 ± 30 mg, P <0.0001) and lower urate clearance (3.7 ± 1.2 mL/min/1.73 m 2 vs. 6.0 ± 2.8 mL/min/1.73 m 2, P <0.0001) than did those without gout (n = 84). Blood lead levels and body lead burden of all subjects were within the safe range. In analyses that adjusted for age, sex, body mass index, protein intake, and creatinine clearance, blood lead level was significantly related to serum urate level (β coefficient [± SE] = 0.23 ± 0.11, P = 0.03), and body lead burdens were related to all indices of urate excretion (serum urate: β coefficient = 0.023 ± 0.005, P <0.0001; daily urate excretion: β coefficient = −1.55 ± 0.40, P = 0.0002; urate clearance: β coefficient = −0.030 ± 0.006, P <0.0001; fractional urate excretion: β coefficient= −0.034 ± 0.006, P <0.0001). Following lead chelation therapy, urate clearance increased after body lead burden was reduced (3.4 ± 1.2 mL/min/1.73 m 2 vs. 4.9 ± 1.4 mL/min/1.73 m 2, P <0.005). Conclusion Chronic low-level environmental lead exposure may inhibit urate excretion in the general population, and lead chelation therapy reduces this inhibition. These findings support efforts to reduce sources of environmental lead exposure and suggest alternative approaches to hyperuricemia and gout in the general population.

Lead chelation therapy and urate excretion in patients with chronic renal diseases and gout

It is known that chronic renal insufficiency (CRI) patients with gout may have subtle lead poisoning. In addition, gout episodes frequently aggravate progressive renal insufficiency because of the use of nephrotoxic drugs and urate deposition. Our study was arranged to evaluate the causal effect of environmental lead exposure on urate excretion in CRI patients. A cross-section study and a randomized, controlled trial were performed. Initially, 101 patients with CRI and without a history of previous lead exposure received ethylenediaminetetraacetic acid mobilization tests to assess body lead stores (BLS). Then, a clinical trial was performed; 30 CRI patients with gout and high-normal BLS and the changes of urate excretion in these patients were compared before and after lead chelating therapy. The treated group received four-week chelating therapy, and the control group received a placebo therapy. The BLS of patients with CRI and gout was higher than that of patients with CRI only, and none had subtle lead poisoning. The BLS, not the blood lead level (BLL), significantly correlated to indices of urate excretion in all CRI patients after related factors were adjusted. In addition, after lead chelating therapy, urate clearance markedly improved after a reduction of the BLS of patients with CRI and gout (study group 67.9 +/- 80.0% vs. control group 1.2 +/- 34.0%, P = 0.0056). Our findings suggest that the chronic low-level environmental lead exposure may interfere with urate excretion of CRI patients. Importantly, the inhibition of urate excretion can be markedly improved by lead chelating therapies. These data shed light on additional treatment of CRI patients with gout; however, more studies are needed to confirm our findings.

Leaded gasoline abuse: the role of tetraethyl lead.

Volatile substance abuse is practised worldwide however reports of the abuse of leaded gasoline have been limited to northern Canada, southwestern USA and the Australian Outback. Chronic, heavy abuse of leaded gasoline results in an encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental status alterations, and persistent organic psychosis. Much of this is due to the hydrocarbons of gasoline while the tetraethyl lead contributes to the altered mental status and is responsible for the persistent psychosis. Lead chelation therapy is not rational and has not been shown to benefit these patients.

Pediatrics academy issues recommendations for lead chelation therapy

Pediatrics academy issues recommendations for lead chelation therapy

A longitudinal study of chronic lead exposure and physical growth in Boston children.

We investigated the cross-sectional and longitudinal relationships between chronic exposure to lead and physical growth among a cohort of children reassessed 13 years after initial examination. We measured weight, height, and dentin lead levels of 270 children in 1975-78. In 1989-1990 we reexamined 79 of these children for measurement of weight, height, and bone lead levels by means of in vivo K X-ray fluorescence. To avoid potential confounding by race and chelation history, analysis was restricted to white subjects without a history of lead chelation therapy. A total of 236 subjects provided complete information for the study of cross-sectional relationship between dentin lead levels and changes in physical growth: 58 subjects for the study of longitudinal relationship between dentin lead levels and changes in physical growth and 54 subjects for the study of longitudinal relationship between bone lead levels and changes in physical growth. Dentin lead levels averaged 14.9 micrograms/g; tibia and patella lead levels averaged 1.2 and 5.0 micrograms/g, respectively. With control for potential confounders including age, sex, baseline body size, and mother's socioeconomic status, log10 dentin lead level was positively associated with body mass index as of 1975-1978 (beta = 1.02, p = 0.03) and increase in body mass index between 1975-78 and 1989-90 (beta = 2.65, p = 0.03). Bone lead levels were not significantly associated with physical growth. This is the first study relating chronic lead exposure to body mass index. The results suggest that chronic lead exposure in childhood may result in obesity that persists into adulthood.

Chelation Therapy in Lead Nephropathy Questioned

To the Editor. —I was concerned when I read the account in theArchivesby Germain et al 1 of attempted lead chelation therapy in an elderly patient with progressive renal insufficiency. Several factors that could have either explained or contributed to this condition were cited, including lead "exposure," the extent or magnitude of which was not specified. Even though the initial blood lead level was only 10 μg/dL of blood, the authors administered edetic acid (EDTA), allegedly to improve the patient's renal function. It is not clear why the authors perceived that increasing the renal lead burden would help seriously compromised kidneys. Indeed, the Occupational Safety and Health Administration, in its lead standard, condemns the administration of this agent in lead-exposed individuals under circumstances other than those in which the overriding medical concern justifies the wellknown renal risks associated with the drug's administration. Edetic acid itself is nephrotoxic, as