The Renal Excretion of Oxypurines*

The mechanism whereby oxypurines (xanthine and hypoxanthine) are excreted by the human kidney is relevant to several areas of current in-vestigation. The use of the xanthine oxidase in-hibitor allopurinol 1 (4-hydroxypyrazolo (3, 4-d)-pyrimidine) as an adjunct to cancer chemotherapy (1) and in the treatment of hyperuricemia asso-ciated with gout (2, 3) results in the accumula-tion of oxypurines that would normally be de-graded to uric acid. The fate of these metabo-lites is pertinent to the clinical use of such an agent. Study of oxypurine clearance by the nor-mal kidney is also of considerable importance in helping to define the precise derangement of oxy-purine metabolism in patients with xanthinuria (4). Dickinson and Smellie have proposed (5) that along with deficient activity of the enzyme xanthine oxidase, these patients may have a de-fect in the reabsorption of xanthine by the renal tubule to account for the high clearance ratio of oxypurine to creatinine found in their patient. Accordingly, a "combined renal and general meta-bolic defect " has been postulated to occur. By examining the renal clearance of oxypurines in normal subjects at serum concentrations approxi-mating those of a xanthinuric patient, this hy-pothesis can be adequately tested. In the present study, the renal clearance of oxy-purines was examined in gouty subjects without renal disease, as well as in one patient with xanthinuria and one normal volunteer. Serum concentrations of oxypurines were augmented by * Submitted for publication September 28, 1964; ac-