Renal handling of urate in healthy man in hyperuricaemia and renal insufficiency: circadian fluctuation, effect of water diuresis and of uricosuric agents

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Abstract
To differentiate between extrarenal and renal causes of hyperuricemia and gout, clearances of urate and creatinine were monitored for 3 1/2 days in 52 individuals (7 with a history of gout) with no gross impairment of renal function (creatinine clearance 52-137 ml/min). Dietary purine intake was kept constant. Monophasic circadian fluctuations of fractional urate excretion (= urate clearance over creatinine clearance) were observed with peak values in the afternoon, .apprx. 50% higher than during the night. Circadian fluctuations of urinary flow rate were almost identical. Enhancement of urinary flow rate due to water diuresis had no effect on urate clearance. Despite wide variation of plasma urate concentrations among different individuals (.+-. 30% SD), daily urate excretion varied little (.+-. 4% SD) and did not correlate with plasma urate (r = 0.03). Extrarenal factors appear not to account for the occurrence of hyperuricemia in these patients. A clearcut negative correlation was apparent between plasma urate concentration and fractional urate clearance (r = 0.72), which could fully account for the variations of plasma urate concentration. To elucidate further the mechanism responsible for antiuricosuria in hyperuricemic patients, the effects of the uricosuric agents benzbromarone and probenecid were tested. A clearcut correlation was apparent between control fractional urate excretion and uricosuric effect of benzbromarone and probenecid (r = 0.83 and 0.88, respectively), suggested that anti-uricosuria was due to defective secretion. In an additional series, the uricosuric effect of probenecid was tested in 10 patients with renal insufficiency. In these patients, the uricosuric effect was clearly blunted, indicating that urate reabsorption is reduced in renal insufficiency.

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