Allopurinol in the prophylaxis of uric acid stones.

Rational prophylaxis of uric acid lithiasis comprises two principles: increase of uric acid solubility in the urine achieved by raising the urinary pH (Peters and Van Slyke, 1946; Prien, 1955; Sperling and de Vries, 1964), and decrease of urinary uric acid (UUA) concentration, achieved by raising urine volume and decrease of UUA excretion. Whereas a rise inurinarypH is easily attained by oral alkalinization therapy (Atsmon, -de Vries, and Frank, 1963; Kollwitz, 1964; Schmidt and Planz, 1965), two measures are available to decrease UUA concentration-high fluid intake and decrease in uric acid production, the latter having become recently feasible with the advent of the xanthine oxidase inhibitor, allopurinol (Wyngaarden, Rundles, Silberman, and Hunter, 1963). Satisfactory results have been reported in the literature in the prophylaxis of uric acid lithiasis by allopurinol in primary and secondary gout (Rundles, Silberman, Hitchings, and Elion, 1964; Yu and Gutman, 1964; Rundles, Metz, and Silberman, 1966b). In the present communication we wish to report on the treatment by allopurinol of non-gouty uric acid stone patients (Cases 1-7), and of one gouty patient with malignant uric acid lithiasis (Case 8). The therapeutic results of allopurinol administration in the seven non-gouty uric acid stone patients (one female and six males) are presented in Table I. The age at which the urolithiasis first manifested itself ranged from 20 to 57 years. All patients had passed innumerable pure uric acid stones and "sand"; only two (Cases 1 and 6) had in addition voided a few stones also containing calcium salts. Two patients (Cases 5 and 6) had periods of urinary tract infection. All seven patients had good kidney function during the whole period of follow up, their creatinine clearances at the start of allopurinol treatment ranging from'105 to 130 ml./min. Alkalinization combined with high fluid intake had been satisfactory for prolonged periods in all but Case 6, who, did not apparently, persistently adhere to the regime. Five patients did well on 300 to 600 mg. allopurinol for periods of 10 to 14 months, when repeat intravenous urography was normal in all. Allopurinol treatment had to be stopped early in Case 7 because of severe pruritus, and after 11 months in Case 6 because of leucopenia (total leucocyte count 2,200/mm.3); in both patients these sideeffects occurred after the dose had been raised to 600 mg. per day. In Case 6 x-ray evidence for a new stone was obtained after an attack of colic, 6 months after treatment with 300 mg. allopurinol per day. Relevant laboratory data obtained during allopurinol treatment are given in Table II (overleaf). In the period of alkalinization, ranging from 3 to 9 years, four patients showed hyperuricaemia (9 * 1, 7 * 7, 7 * 7, 7-1 mg./100 ml.)*, and three showed hyperuricosuria (1,140 to 1,600 mg./day). Interestingly, two of these hyperuricosuric patients (Cases 4 and 6) produced stones in the alkalinization period, but whether this stone formation was related to the hyperuricosuria cannot be decided, since both had also had at one time or another a very low urinary pH, presumably related to inadequate regime. During a short-lasting base-line period preceding allopurinol treatment, urinary pH reached low values in all patients and in all but one uric acid crystals appeared in the urine, in most in excessive amounts. Allopurinol decreased UUA excretion *We regard 3 to 6-4 mg./100 ml. as normal.