We measured urinary enzyme activities, such as urinary-γ-glutamyl transpeptidase (U-γ-GTP) and microalbumin in 77 gouty patients without overt protei nuria, hypertension or diabetes mellitus in order to estimate renal derangement associated with gout, and investigated the relationship between these parameters and other renal function tests. Mean U-γ-GTP index was significantly higher in gouty patients than that in control subjects (p< 0.01), and U-γ-GTP index over 48 U/g⋅Cr was seen in 45.5% of gouty patients. Microalbuminuria, and elevated levels of urinary alanine aminopeptidase(U-AAP), urinary N-acetyl-β-glucosaminidase(U-NAG), urinary β₂-microglobulin(U-β₂-MG) and serum β₂-microglobulin(S-β₂-MG) were noted in 12.9%,11.7%,7.8%,5.2% and 6.5%of the gouty patients, respectively.
The levels of S-β₂-MG and U-β₂-MG were not different for patients with U-γ-GTP index of more than 48 U/g⋅Cr and those with U-γ-GTP index of less than 48U/g⋅Cr. However, a high level of U-NAG and significantly low level of Ccr were noted in patients having U-γ-GTP index over 48 U/g⋅Cr. The results of Fishberg's concentration test were not different for the two groups. As a result, it is considered to be desirable to perform simultaneous measurement of U-γ-GTP, U-NAG and U-β₂-MG in evaluating whether or not proximal tubular damage really exists in gouty patients. In addition, microalbuminuria over 15μg/ml was seen in some patients without elevated levels of S-β₂-MG. Therefore, it is suggested that microalbuminuria level is a sensitive indicator of renal damage, especially that of the glomerulus. However, whether microalbuminuria level can be used to predict the progression of gouty nephropathy remains unclear and will require long-term follow-up studies.

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5-n-Butyl-1-cyclohexy1-2,4,6-trioxo-perhydropyrimidine, or bucolome (BCP) has been found to cause uric acid excretion. Aspirin ( ASA ) is also known to affect uric acid excretion by the kidneys.
In the present study, we evaluated the effect of ASA on serum uric acid level and urinary uric acid excretion, both of which are enhanced by BCP. Subjects were 24 healthy males, who were divided into three groups on the basis of drug administration, as follows:
Group 1.: single oral administration of 600 mg of BCP only Group
2.: simultaneous administration of 600 mg of BCP and 990 mg of ASA Group
3.: administration of 2,970 mg of ASA, followed by 600 mg of BCP and 990 mg of ASA on the next day
Group 1 showed a significant reduction in serum uric acid level and an increase in urinary uric acid excretion - hours after administration. The rise in urinary uric acid excretion coincided with the peak in the serum BCP concentration.
In Group 2, BCP concentration showed a tendency to decrease, while the reduction in serum uric acid level-hours after administration and increase in urinary uric acid excretion - hours after administration were found to be less prominent than in Group 1.
In Group 3, the serum ASA level showed a peak of 98.4±19.8μg/ml within one hour, while the blood level of BCP at that time was significantly reduced. In addition, a transient increase in uric acid excretion at 0 to 2 hours after administration was noted, suggesting dysfunction of uric acid reabsorption associated with ASA.
Subsequently, urinary uric acid excretion peaked at 4 to 6 hours after administration. The peak was suspected to be due to the action of BCP, although the rise was insignificant. Serum uric acid level remained unchanged.

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The effect of diltiazem on renal uric acid excretion was investigated in urethane anesthetized oxonate - loaded rats. Oxonate - loading was performed by continuous intravenous infusion. Renal function was studied by measuring clearance, and renal blood flow was measured with a laser Doppler flowmeter.
Diltiazem (0.3 mg/kg, i.v.) slightly increased urine volume, remarkably increased urinary excretion of uric acid and uric acid clearance, and showed a tendency to increase glomerular filtration rate and fractional uric acid clearance. It had no effect on plasma uric acid level. In addition, diltiazem induced an increase following a transient decrease in renal cortical blood flow, the decrease was probably due to a drop in blood pressure after i. v. injection.
These data suggest that diltiazem has a uricosuric action and that the mechanism of action of the compound may be related to changes in renal hemodynamics.

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Oxypurines are precursors of uric acid and are important metabolic intermediates which regulate uric acid synthesis. The myogenic and hepatogenic mechanisms for the pathogenesis of hyperoxypurinemia associated with hyperuricemia in various type of glycogenosis were investigated in this study.
The myogenic mechanism was investigated in patients with glycogenosis types III, V and VII, mitochondrial myopathy (Kearns-Sayre syndrome), hypoparathyroidism and hypothyroidism. During/after bicycle-ergometer exercise, plasma and urinary concentrations of inosine and hypoxanthine increased markedly. The semiischemic forearm exercise test, demonstrated that inosine and hypoxanthine were produced through excess purine degradation in exercising muscles.
The hepatogenic mechanism was investigated in a patient with glycogenosis type I. During/after glucagon-loading test, the plasma inorganic phosphate concentration decreased, and plasma and urinary concentrations of both hypoxanthine and xanthine increased markedly. Continuous glycogen breakdown following glucagon injection together with impaired glucose -6-phosphate hydrolysis due to glucose-6-phosphatase deficiency is known to result in a decrease in inorganic phosphate concentration in the liver. The depletion of inorganic phosphate accelerates purine degradation in the liver through deinhibition of both 5'-nucleotidase and AMP deaminase. Thus, hyperoxypurinemia due to a myogenic mechanism occurs only after exercise, and the plasma xanthine concentration increases slightly, in contrast to a marked increase in plasma hypoxanthine. On the other hand, hyperoxypurinemia due to a hepatogenic mechanism is manifest when the plasma glucose level is low, and the increase in oxypurine concentrationis predominant in the xanthine rather than the hypoxanthine component.

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