GOUTY DIATHESIS--PATHOPHYSIOLOGY AND MOLECULAR GENETIC BASIS

$0P01FY2000DKNIH

University Of Texas Sw Med Ctr/Dallas, Dallas TX

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Abstract

Description: (Taken directly from the application) A disturbance in urate metabolism has been shown to lead to the development of both uric acid and calcium stones. In addition, primary gout is frequently observed with uric acid lithiasis, where undue urinary pH from defective ammonium production is believed to promote uric acid crystallization. We have used the term gouty diathesis to describe stone formation associate with primary gout, and that it is comprised of acquired and primary (genetic) variants. This hypothesis will be tested by (1) assessing whether defective ammonium production in gouty diathesis is evident by controlling acid intake and imposing phosphate restriction and that, in the acquired form of the disease, insulin resistance is responsible for undue acidity and other biochemical features of this disease, and (2) identifying the molecular defect in the "primary" genetic form of the disease. These studies will help elucidate the pathophysiology of gouty diathesis and may lead to improvements in the diagnosis and treatment of this form of urolithiasis.

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