Lead nephropathy exposure

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

Chronic high-dose lead exposure, usually associated with months to years of blood lead concentrations in excess of 80 g/dL, may result in renal interstitial fibrosis and nephrosclerosis. Lead nephropathy may have a latency period of years. Lead may alter uric acid excretion by the kidney, resulting in recurrent bouts of gouty arthritis ("saturnine gout"). Acute high-dose lead exposure sometimes produces transient azotemia, possibly as a consequence of intrarenal vasoconstriction. 

The exposure to lead based paints and subsequent lead nephropathy and encephalopathy, in the USA, is concentrated in substandard housing [162]. Individuals at the lower end of our economic ladder often are denied access to preventative health care thus putting them at additional risk for toxin exposure. Another example is the consumption of "moonshine" whiskey that has been associated with the development of lead nephropathy [167]. 

The increase in urinary N-acetyl- -D-glucosamini-dase (NAG) with increasing blood lead concentrations reflects the proximal tubule dysfunction seen in acute lead nephropathy rather than the chronic interstitial nephritis associated with occupational lead exposure [35, 36]. NAG excretion correlates positively with the blood lead concentration but not with the bone lead concentration [37]. Eicosanoid excretion in lead workers is similar to that in patients with essential... 

Hyperuricemia and gout are common among individuals with excessive exposure to lead, apparently the result of decreased excretion and increased production of uric acid. Although hyperuricemia invariably accompanies azotemia, gout is uncommon in patients with renal failure except in those with lead nephropathy. Half of uremic patients with lead nephropathy have clinical gout [18] but in the absence of renal failure, gout cannot usually be attributed to lead despite coexisting hypertension [23, 37]. 

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]. 

Clinically, lead nephropathy is seen as either reversible tubular dysfunction or as an irreversible interstitial nephropathy. Tubular toxicity occurs most commonly in children following acute exposure and is characterized by glucosuria, phosphaturia, aminoaciduria, and occasionally proteinuria. One unique morphological feature of lead exposure is the formation of nuclear inclusion bodies within renal tubular cells. These bodies are complexes between lead... 

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. 

Chronic lead nephropathy in the occupational setting has been noted for many years, but the lead dosimetry in early studies was generally poorly characterized (Eimnerson 1973 Cramer et al. 1974 Wedeen et al. 1975). Most of the occupational studies have been small and have failed to consider other important confounders of the association between lead exposure and renal function adequately. In addition, the healthy-woiker effecf which is probably pronounced in industries in which health surveillance is required, may bias possible associations toward the null (Ekong et al. 2006). 

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. 

CHRONIC LEAD NEPHROPATHY IN ADULTS WITH OCCUPATIONAL EXPOSURES... 

TABLE 15.3 Illustrative Studies of Chronic Lead Nephropathy in Workers with High Occupational Lead Exposures ... 

Khalil-Manesh, F., Gonick, H.C., Cohen, A., Bergamaschi, E., Mutti, A., 1992b. Experimental model of lead nephropathy. 11. Effeet of removal from lead exposure and chelation treatment with dimercaptosuccinic acid (DMSA). Environ. Res. 58, 35—54. 

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Taken together, these studies provide some evidence for the association of chronic nephropathy in occupationally exposed workers with PbB levels ranging from 60 to >100 pg/dL. It should be noted, however, that PbB levels measured at the time of renal function testing may not fully reflect the exposure history that contributed to the development of chronic nephropathy in lead workers. 

Chia KS, Jeyaratnam J, Lee J, et al. 1995b. Lead-induced nephropathy Relationship between various biological exposure indices and early markers of nephrotoxicity. Am J Ind Med 27 883 895. 

Lilis R. 1981. Long-term occupational lead exposure, chronic nephropathy, and renal cancer A case report. Am J Ind Med 2 293-297. 

Male rats are sensitive to renal tubular nephropathy after exposure to hexachloroethane. The lesions observed are characteristic of hyaline droplet nephropathy. They are most likely the result of hexachloroethane or one of its metabolites binding to the excretory protein 2p-globulin, altering its kidney transport, and leading to the formation of hyaline droplets. This protein is synthesized by male rats and accounts for 26% of their urinary protein excretion (Olson et al. 1990). It is not excreted in female rats except in minimal quantities. Since some effects are also seen in kidneys of female rats and in male and female mice that do not synthesize 2p-globulin, hexachloroethane must also have milder adverse effects on the kidney through a different mechanism. 

Nephropathy has been associated with chronic lead poisoning. " A study of two large cohorts of heavily exposed lead workers followed through 1980 demonstrated a nearly threefold excess of deaths attributed to chronic nephritis or other hypertensive disease, primarily kidney disease. Most of the excess deaths occurred before 1970, among men who began work before 1946, suggesting that current lower levels of exposure may reduce the risk. Experimental animal studies suggest there may be a threshold for lead nephrotoxicity, and in workers, nephropathy occurred only in those with blood levels over 62p,g/dl for up to 12 years."... 

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