Lead nephropathy chelation therapy

A study of 55 adolescents who had been treated for lead intoxication in early childhood (11-17 years earlier) revealed no evidence of chronic nephropathy, as evidenced by endogenous creatinine clearance, BUN, serum uric acid, and routine urinalysis (Chisolm et al. 1976). PbB levels during the acute poisoning episode ranged from 100 to 650 pg/dL all patients received immediate chelation therapy. At the time of the study, their PbB levels had decreased to less than 40 pg/dL. 

In children with lead encephalopathy, proximal tubule reabsorptive defects characterized by the Fanconi syndrome have been observed [13]. The Fanconi syndrome appears when blood lead levels approach 150 //g/ dL. It is rapidly reversed by chelation therapy designed to treat the far more dangerous lead encephalopathy. The proximal tubule reabsorptive defect can regularly be induced experimentally in rats fed dietary lead [14]. In both children and experimental animals, acute lead nephropathy is consistently associated with acid-fast intranuclear inclusions in proximal tubule... 

Lead nephropathy is important because it is one of the few renal diseases that is preventable. Moreover, lead-induced acute renal dysfunction can sometimes be reversed by chelation therapy [19, 28, 63]. The salutary effect of chelation therapy appears to be on the acute reduction in GFR and the acute elevation of blood pressure associated with elevated blood lead concentration rather than on the long-term effects of cumulative exposure associated with endothelial dysfunction, hypertension, and interstitial nephritis. There is no evidence that such therapy reverses established interstitial nephritis. The partial remission achieved among moonshiners and lead workers appears to represent reversal of the physiologic effects of acute poisoning superimposed on chronic lead nephropathy. No improvement in renal function has been observed once advanced interstitial nephritis is present and the steady-state serum creatinine concentration exceeds about 3 mg/ dL [64]. 

Germain MJ, Braden GL, Eitzgibbons JP. Eailure of chelation therapy in lead nephropathy. Arch Intern Med 1984 144 2419-2420. 

Chronic exposure to low levels of lead results in lead accumulation within the body. Workers who have been chronically exposed to lead develop interstitial fibrosis, vascular and glomerular sclerosis, and tubular atrophy and/or hypertrophy. Although acute lead nephropathy is reversible with chelator therapy and/or removal from exposure, chronic effects may be irreversible. In addition, chronic exposure to lead may result in a gouty nephropathy as lead reduces uric acid excretion and elevates blood uric acid levels. 

Although chelation therapy effectively reverses acute lead nephropathy and the preclinical renal dysfunction of occupational lead nephropathy, there is no evidence that such therapy reverses established interstitial nephritis due to lead. The partial remissions achieved among moonshiners and symptomatic lead workers may represent reversal of acute poisoning superimposed on chronic lead nephropathy. No improvement in renal function can be expected once ad-... 

Examination of Pb mobilization data through provocative chelation or chelation therapy plumburesis (Chisolm et al., 1976 Emmerson, 1963) showed large bone Pb stores in the Queensland young adults, while bone Pb concentrations in these nephropathy patients years after the lead paint exposures were also quite high. The mean bone Pb content reported by Inglis et al. (1978) for such patients rivals that reported for individuals with high occupational Pb exposures. 

Penicillamine is a chelating agent which binds copper, mercury, zinc, and lead. It has been used to treat poisoning from these chemicals and also for disorders of copper metabolism such as Wilson s disease and primary biliary cirrhosis. Penicillamine has been tried in scleroderma and arthritis. Hypersensitivity reactions are common. About 20%-30% of the patients show hypersensitivity reactions suchs as morbilliform exanthema, urticaria, purpura, anorexia, lymphadenopathy, leukopenia, and thrombocytopenia (Meyboom 1975 Balme and Huskisson 1977). More severe skin symptoms associated with penicillamine therapy are Stevens-Johnson syndrome, pemphigus, myasthenia gravis, cholestatic jaundice (Barzilai et al. 1978), nephropathy (Lange 1978) and lupus-like syndrome (Harpey et al. 1972). 

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