Lead nephropathy experimental

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-induced hyperuricemia may contribute to chronic lead nephropathy. Uric acid per se induces endothelial cell injury, renal microvascular disease, and hypertension, at least in part mediated by oxidative stress [38]. Independent of uric acid, reactive oxygen species induced by lead have been imphcated in endothelial cell injury, increased vascular reactivity, and the production of hypertension in humans and experimental animals [39]. 

Scinchez-Fructuoso Al, Blanco J, Montserrat C, Ortega L, Arroyo M, Fernandez C, Prats D, Barrientos A. Experimental lead nephropathy treatment with calcium disodium ethylenediaminetetraacetate. Am J Kidney Dis 2002 40 59-67. Scinchez-Fructuoso Al, Toralbo A, Arroyo M, Lunque M, Ruilope LM, Santos JL, Cruceyra A, Barrientos A. Occult lead intoxication as a cause of hypertension and renal failure. Nephrol Dial Transplant 1996 11 1775-1780. 

TABLE 15.8 Illustrative Experimental Animal Studies of Lead Nephropathy... 

Khalil-Manesh, F., Gonick, H.C., Cohen, A.H., Alinovi, R., Bergamaschi, E., Mutti, A., et al., 1992a. Experimental model of lead nephropathy. I. Continuous high-dose lead administration. Kidney Int. 41, 1192—1203. 

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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