oxypurinol and Kidney-Calculi

The spectrum of kidney and urinary tract disorders related to purines comprises acute hyperuricosuric nephropathy, chronic urate nephropathy and urolithiasis. Two factors in the development of acute hyperuricosuric nephropathy are increased uric acid concentration and low pH in the tubular fluid. Chronic urate nephropathy still possess several problems: incidence (although this seems to be decreasing, presumably owing to effective prevention), the source of interstitial urate, the cause of the interstitial deposition of urate, and the role of urate deposits in the pathogenesis of the interstitial nephropathy. The relation of the experimental nephropathy to the pathogenesis of chronic urate nephropathy in the human is not yet clear but a model is proposed according to which interstitial urate derives from two sources: hyperuricaemic plasma and hyperuricosuric tubular fluid. Urolithiasis related to purines leads to uric acid-urate stones, xanthine stones, 2,8-dihydroxyadenine stones, iatrogenic xanthine and oxipurinol stones, and possibly calcium stones. Pathogenetic factors in uric acid lithiasis are hyperuricosuria (whether due to an inborn enzyme abnormality or of unknown aetiology) and low urinary pH; oliguria is a contributory factor. There remain several open questions about uric acid lithiasis: incidence, the shift of its location from lower to upper urinary tract, the interplay of pathogenetic factors, and the role of compounds which inhibit crystallization.

Topics: Adenine Phosphoribosyltransferase; Allopurinol; Animals; Calcium; Gout; Humans; Hydrogen-Ion Concentration; Hypoxanthine Phosphoribosyltransferase; Kidney Calculi; Kidney Diseases; Kidney Failure, Chronic; Oxypurinol; Purines; Sodium; Solubility; Uric Acid; Urologic Diseases; Xanthine Oxidase; Xanthines

The authors report a case of xanthine stones in a 12-year-old child with Lesh Nyhan syndrome treated by allopurinol at the dose of 10 mg/kg/24 hours. This type of urinary stone is unusual and its structure was confirmed by spectrophotometric analysis. This type of stone, in the context of Lesh Nyhan syndrome, suggests the presence of allopurinol treatment. Discontinuation of this treatment prevents recurrence of xanthine stones.

Topics: Allopurinol; Antimetabolites; Child; Enzyme Inhibitors; Follow-Up Studies; Humans; Kidney Calculi; Lesch-Nyhan Syndrome; Male; Oxypurinol; Spectrophotometry; Urinary Bladder Calculi; Xanthine; Xanthines

We report a case of urate overproduction owing to the Lesch-Nyhan syndrome (deficiency of hypoxanthine-guanine phosphoribosyltransferase). Urate crystalluria was controlled by allopurinol therapy but renal calculi developed, which contained a variety of purines, particularly the relatively insoluble xanthine, as well as oxypurinol and hypoxanthine. The potential hazard from the increased amounts of xanthine that are produced during allopurinol therapy for urate overproduction is stressed, as well as the importance of maintaining a high urine flow rate even during such therapy.

Topics: Adult; Allopurinol; Humans; Hypoxanthine; Hypoxanthines; Kidney Calculi; Lesch-Nyhan Syndrome; Male; Oxypurinol; Uric Acid; Xanthine; Xanthines

A patient with regional enteritis and recurrent uric acid nephrolithiasis was treated with allopurinol. While on 600 mg of allopurinol daily, she began to pass many small, soft, yellow stones. Analysis of the stones by liquid chromatographic and gas chromatograph/mass spectrometric techniques revealed that their major constituent was oxypurinol, a metabolite of allopurinol. Metabolic studies of the patient indicated that increasing doses of allopurinol were associated with increases in xanthine and oxypurinol excretion, while uric acid excretion was not reduced. This case illustrates a complication of high-dose allopurinol therapy in the treatment of uric acid nephrolithiasis.

Topics: Adult; Allopurinol; Crohn Disease; Female; Humans; Kidney Calculi; Oxypurinol; Pyrimidines; Uric Acid; Xanthines

Solubility measurements, seeded crystal growth kinetics, solution depletion adsorption studies, nucleation observations, zeta potential measurements, and measurements of in vivo intrarenal crystallization all failed to show that either oxipurinol or allopurinol riboside interacts with calcium, oxalate, or whewellite (CaC2O4.H2O) at concentrations expected in therapeutic situations. We conclude that at therapeutically expected concentrations, oxipurinol and allopurinol riboside do not affect crystallization of calcium oxalate.

Topics: Allopurinol; Animals; Calcium Oxalate; Crystallization; In Vitro Techniques; Kidney Calculi; Kinetics; Oxalates; Oxypurinol; Pyrimidines; Rats; Ribonucleosides