Consumption of alcoholic beverages is associated with hyperuricemia and gout. To determine the contributions to this process of increased production and decreased excretion of uric acid, we gave oral ethanol (1.8 g per kilogram of body weight every 24 hours) for eight days or intravenous ethanol (0.25 to 0.35 g per kilogram per hour) for two hours to six patients with gout. During the long-term oral study we observed the following: serum urate levels increased from 8.4 +/- 0.4 (mean +/- S.E.) to 10.1 +/- 0.9 mg per deciliter; whole blood lactate reached a peak of 3.1 +/- 0.7 mM from a base line of 1.3 +/- 0.3 mM; and urinary oxypurines increased to 641 +/- 397 per cent of the base-line value. Urate clearance increased to 145 +/- 25 per cent of the base-line value. Daily uric acid turnover increased from 1010 mg per deciliter to 170 +/- 17 per cent of the base-line value. During short-term intravenous ethanol administration, serum urate levels, urate clearance, and urinary uric acid excretion were not substantially altered from the base-line period. Urinary oxypurine levels increased to 341 to 415 per cent of base-line values. Urinary radioactivity, originating from the adenine nucleotide pool labeled by [8-(14)C]adenine, increased to 127 to 149 per cent of base-line values. These data indicate that ethanol increases urate synthesis by enhancing the turnover of adenine nucleotides.

To evaluate the frequency and the pathogenesis of hyperuricemia and gout during cyclosporine therapy, we studied renal-transplant recipients who were treated with either cyclosporine and prednisone (n = 129) or azathioprine and prednisone (n = 168). Among the patients with stable allograft function and serum creatinine concentrations below 265 mumol per liter, hyperuricemia was more common in the cyclosporine group than in the azathioprine group (84 percent vs. 30 percent; P = 0.0001). Gout developed in nine patients (7 percent) in the cyclosporine group, but no episodes occurred in the azathioprine group. Serum urate levels became elevated in 90 percent of the patients in the cyclosporine group who were treated with diuretics, as compared with 60 percent of those not treated with diuretics (P = 0.001); in the azathioprine group, the corresponding values were 47 percent and 15 percent (P = 0.0001). Serum urate levels did not correlate with trough blood cyclosporine levels in a selected subgroup (n = 40) of patients from the cyclosporine group, who were studied from 4 to 96 weeks after transplantation. Detailed studies of urate metabolism in six cyclosporine-treated patients revealed normal turnover rates for urate and decreases in creatinine and urate clearance, as compared with seven control subjects. We conclude that hyperuricemia is a common complication of cyclosporine therapy and is caused by decreased renal urate clearance. Gouty arthritis is the cause of considerable morbidity among renal-transplant recipients who receive cyclosporine.