Cyclosporine-Induced Hyperuricemia and Gout

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 μmol 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. (N Engl J Med 1989; 321:287–92.) DURING the course of one month, three recipients of renal allografts presented to our services with acute gouty arthritis. All three were receiving cyclosporine and prednisone for maintenance immunosuppression. A review of the literature at that time revealed a few reports of cyclosporine-related hyperuricemia. 1 2 3 4 5 6 To define better the relation between cyclosporine use and hyperuricemia, we initiated a study to investigate two questions: What is the prevalence of hyperuricemia and of gout among patients treated with cyclosporine? and What is the mechanism of cyclosporine-associated hyperuricemia? Our study of 297 renal-allograft recipients allowed us to address these questions systematically. Methods Selection and . . .