Hyperuricemia lead nephropathy

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-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]. 

Of particular interest was the fact that the cohort surviving into the 1%0 s had developed a high prevalence of gouty arthritis in comparison with patients with chronic nephritis due to causes other than lead. There was also a disproportionate hyperuricemia in these patients with chronic lead nephropathy, which was caused by a significantly lower urate clearance for any particular degree of renal insufficiency [32]. Studies of discrete tubular functions suggest that this was due to excessive reabsorption of filtered urate [33]. 

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

Khoury et al., 1996 Locatelli et al., 1993, 2000). Pest infestation of dried fish leads to higher levels of uric acid and bacterial counts that are unacceptable to consumers and traders (Solanki, 1985). Toxicological studies revealed that excess levels of uric acid in the diet could induce hyperuricemia with associated nephropathy in rats (Starvic et al., 1969). Secretions from the adults of Tribolium spp. and Rhyzopertha dominica impart unacceptable off-odors to foodstuffs. Processing and end-use qualities of food commodities are also affected by insect infestation, as are cash value and marketability of different commodities. 

Renal Disease is a well recognized complication of gout, and the typical histologic features of chronic gouty nephropathy have been carefully studied, however, early evolution of the nephropathy and its precise relationship to hyperuricemia and uricosuria have been difficult to study in the human subject. Unfortunately, animal models of sustained hyperuricemia are difficult to produce and maintain. Recently, Stavric and colleagues described the production of hyperuricemia and urate nephropathy in rats fed orally with oxonic acid and uric acid, oxonic acid is a potent, hepatic uricase inhibitor and this chemical, combined with uric acid or RNA dietry supplements, consistently leads to hyperuricemia in this species. 

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