Methylated Purines in Urinary Stones

Abstract

Background: The aim of the study was to measure the content of methylated purines that appear as admixtures in uric acid stones. Methods: We analyzed urinary calculi from 48 residents of Western Pomerania who underwent surgery at the urology ward in Szczecin. Stone samples were dissolved in 0.1 mol/L NaOH. Extracts were diluted in 50 mmol/L KH 2 PO 4 and analyzed by reversed-phase HPLC with ultraviolet detection and use of a gradient of methanol concentration and pH. Results: Uric acid was the main component of 9 stones. All 9 showed admixtures of 9 other purine derivatives: endogenous purine breakdown products (xanthine, hypoxanthine, and 2,8-dihydroxyadenine) and exogenous methyl derivatives of uric acid and xanthine (1-, 3-, and 7-methyluric acid; 1,3-dimethyluric acid; and 3-and 7-methylxanthine). Amounts of these purine derivatives ranged from the limit of detection to 12 mg/g of stone weight and showed a strong positive correlation (Spearman rank correlation coefficients, 0.63-0.94) with the uric acid content of the samples. The main methylated purine in the stones was 1-methyluric acid. Conclusions: Urinary purines at concentrations below their saturation limits may coprecipitate in samples supersaturated with uric acid and appear as admixtures in urinary stones. The amount of each purine depends on its average urinary excretion, similarity to the chemical structure of uric acid, and concentration of the latter in the stone. These findings suggest that purines in stones represent a substitutional solid solution with uric acid as solvent. Methylxanthines, which are ubiquitous components of the diet, drugs, and uric acid calculi, may be involved in the pathogenesis of urolithiasis. © 2005 American Association for Clinical ChemistryMany purines are poorly soluble in aqueous solutions and may precipitate from urine, forming urinary calculi, if their concentrations exceed the limit of saturation. Uric acid (UA) 1 is the end product of human purine metabolism and is excreted mainly in the urine. Acidic urine is often a supersaturated solution of uric acid, even when the daily output remains in the normal range, and uric acid stones may form. Crystallization is usually prevented by inhibitors (citrates, glycosaminoglycans, and some proteins) (1 ), although not always effectively enough, particularly at low urine pH. Calculi composed of UA also form in males with hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) deficiency (complete or partial). Xanthine (Xan) may appear in xanthinuria as well as during treatment with allopurinol (2 ). 2,8-Dihydroxyadenine (2,8-DHA) is excreted in urine and can precipitate in renal tissue and the urinary tract in patients with dihydroxyadeninuria attributable to adenine phosphoribosyltransferase (EC 2.4.2.7) deficiency (3 ).Limited attention has been paid to the possible role of metabolites of methylxanthines (caffeine, theophylline, and theobromine) in the pathogenesis of urolithiasis, although their average daily output in urine, depending on dietary intake, is ϳ500...

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