1-Methyluric acid

1-Methyluric Acid Nephropathy

An unusual patient with kidney stones composed of 1-methyluric acid

An unusual case with kidney stones composed mainly of 1-methyluric acid is described. The patient, a Caucasian male of Celtic descent, reportedly drank at least eight cups of coffee per day and had a long history of rheumatoid arthritis, gouty attacks and renal colics--the latter attributed to nephrocalcinosis and analgesic nephropathy. He was treated with allopurinol. At 54 years, a bilateral nephrolithotomy was performed. Stone samples were analysed by thermogravimetry and infrared spectroscopy and reported to be 12-25% calcium oxalate, the remainder being organic uric acid-like material. Analysis of the extracts by HPLC confirmed that the organic material contained 67% of 1-methyluric acid and 33% of uric acid. Possible mechanisms leading to the precipitation of 1-methyluric acid from urine are discussed. We conclude that the high caffeine intake resulted in extremely elevated urinary concentrations of 1-methyluric acid favouring the formation of 1-methyluric acid stones.

Tea and coffee consumption and pathophysiology related to kidney stone formation: a systematic review

Objective: To explore the mechanisms behind the potential protective effect of coffee and tea consumption, regarding urinary stone formation, previously demonstrated in large epidemiological studies.
Methods: A systematic review was performed using the Medline, Cochrane library (CENTRAL) and Scopus databases, in concordance with the PRISMA statement. English, French and Spanish language studies, regarding the consumption of caffeinated and decaffeinated coffee and tea, and the relationship to urinary stone formation were reviewed. Meta-analyses, systematic reviews, case reports and letters, unpublished studies, posters and comments abstracts were excluded.
Results: As per the inclusion criteria, 13 studies were included in the final review. The major findings show that caffeine increases urinary excretion of calcium, sodium and magnesium, in addition to a diuretic action with consumption > 300-360 mg (approximately four cups of coffee). Together with other components of coffee, this beverage might have potential protective effects against the formation of urinary stones. Tea exerts many protective effects against stone formation, through the accompanying water intake, the action of caffeine and the effects of components with antioxidant properties.
Conclusion: Caffeine has a hypercalciuric effect, balanced partially by a diuretic effect which appears after consumption of large quantities of caffeine. The current available literature supports in general, a potentially protective role for tea against stone formation, mainly for green tea. Additional standardization in this field of research, through specification of tea and coffee types studied, and their respective compositions, is needed for further clarification of the relation between coffee, tea and urinary stones.

Nonlinear renal excretion of theophylline and its metabolites, 1-methyluric acid and 1,3-dimethyluric acid, in rats

Plasma pharmacokinetics and renal excretion of theophylline (TP) and its metabolites were investigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric (DMU) declined in a biexponential manner upon respective i.v. bolus injection of each compound at 6 mg/kg dose. The total body clearances (CLt) of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state (Vdss) were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after i.v. injection of TP indicating very rapid metabolism of TP. Metabolism of TP to DMU was more than fourfold faster than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance (CLr) of TP was inversely related to plasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The CLr of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion plays a major role in their elimination. The CLr of the metabolites were reduced to less than GFR by i.p. injection of probenecid (142.7 mg/kg). It supports that the metabolites are secreted in the renal tubule, and suggests that they share a common transport system in their secretion processes with probenecid. On the other hand, the CLr of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the CLr and its plasma concentrations, no effect of probenecid on CLr of TP is most likely due to negligible contribution of the secretion to the overall CLr of TP.

Secondary metabolism of theophylline biotransformation products in man--route of formation of 1-methyluric acid

The route of formation of 1-methyluric acid (1MU) from theophylline has been investigated by i.v. administration of 1-methylxanthine (1MX) before and after allopurinol treatment and of 1,3-dimethyluric acid (1,3DMU) to healthy male volunteers. 1,3DMU was recovered unchanged in urine and was not demethylated to 1MU. By contrast after administration of 1MX the major part of the dose was recovered as 1MU. After allopurinol this was reversed with most of the 1MX dose being excreted unchanged and only a minor amount as 1MU. The results show that 1MU derived from theophylline is formed by an initial 3-demethylation to 1MX and then a rapid xanthine oxidase mediated 8-oxidation. No 1MU is formed by 3-demethylation of 1,3DMU.