oxypurinol and Kidney-Diseases

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

A study was conducted to determine whether combination treatment using allopurinol and benzbromarone was more useful than single allopurinol treatment for the gout and hyperuricemia accompanying renal dysfunction. The subjects were 45 male patients who received urate-lowering treatment and showed a stable serum urate level. The patients were divided into four groups according to the urate-lowering treatment and creatinine clearance (Ccr) (A group: single treatment, normofunction, B group: single treatment, hypofunction, C group: combined treatment, normofunction, D group: combined treatment, hypofunction). There were no differences in serum urate levels among the four groups. Urate clearance (CUA)and daily urinary urate excretion (UUAV) showed significantly high values in the C group, but no difference was seen in the fractional excretion of urate (FEUA) among the four groups. The dosage of allopurinol in the D group was significantly lower than in the A and B groups. Serum oxypurinol concentration in the C group was lower than that in the B group. Oxypurinol clearance (C oxypurinol) in the C group was significantly high compared with the B and D groups. There was a close correlation between C oxypurinol, Ccr, and CUA, with an especially strong correlation between C oxypurinol and CUA. There were no differences in the serum concentration and clearance of xanthine and hypoxanthine among the four groups. Results of the study suggested that combination treatment using allopurinol and benzbromarone for the gout and hyperuricemia accompanying renal dysfunction is more useful, because a lower dose of allopurinol can be used and the serum oxypurinol concentration is reduced compared with single allopurinol treatment.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Drug Therapy, Combination; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Oxypurinol; Retrospective Studies

Topics: Allopurinol; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Diseases; Oxidative Stress; Oxypurinol; Uric Acid

Topics: Allopurinol; Female; Humans; Kidney Diseases; Kidney Tubules; Male; Metabolic Clearance Rate; Middle Aged; Oxypurinol; Uric Acid

Allopurinol toxicity has been associated with the use of this drug in patients with renal insufficiency, a situation where the half-life of oxipurinol, the major metabolite of allopurinol, is prolonged. Allopurinol toxicity has also been associated with the concomitant use of allopurinol and thiazide diuretics. In the present study, the effect of hydrochlorothiazide administration on the renal clearance and serum half-life of oxipurinol has been studied in eight normal volunteers to determine if thiazides delay the clearance of oxipurinol. Oxipurinol's renal clearance and serum half-life were measured in each volunteer during a control period and again while the volunteer was receiving 50 mg/day hydrochlorothiazide for 1 week. No change in renal oxipurinol clearance (21.1 +/- 5.9 vs. 20.4 +/- 8.7 ml/min) or serum oxipurinol half-life (23.7 +/- 4.2 vs. 23.4 +/- 4.4 hours) was noted with the addition of thiazides. The association previously noted between the use of thiazide diuretics and the development of allopurinol toxicity cannot be explained by alterations in oxipurinol pharmacokinetics.

Topics: Adolescent; Adult; Allopurinol; Diuretics; Drug Evaluation; Drug Interactions; Half-Life; Humans; Hydrochlorothiazide; Kidney; Kidney Diseases; Kidney Function Tests; Oxypurinol; Sodium Chloride Symporter Inhibitors