To differentiate between extrarenal and renal causes of hyperuricaemia and gout, clearances of urate and creatinine were monitored for 3 1/2 days in fifty-two individuals (seven 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, about 50% higher than during the night. Circadian fluctuations of urinary flow rate were almost identical. However, 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). Thus extrarenal factors appear not to account for the occurrence of hyperuricaemia in these patients. In contrast, 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 hyperuricaemic 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 both benzbromarone and probenecid (r = 0.83 and 0.88, respectively), suggesting that anti-uricosuria was due to defective secretion. In an additional series, the uricosuric effect of probenecid was tested in ten 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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We are reporting about a case of gamma heavy-chain disease (Franklin's disease) with immunovasculitis and rheumatoid arthritis. The diagnosis was confirmed by the results of immunoelectrophoresis of the patient's serum and also by evidence of stimulated lymphocytes without light chain, but having gamma heavy-chain surface proteins. The immunofixation of the serum showed two protein bands of gamma heavy-chains with different loads. These results are confirmed by a two dimensional electrophoresis and isoelectric focussing of the serum proteins. The pathologic protein consists of at least two different heavy-chain proteins (mol wt 40,000 and 80,000) with isoelectric points between pH 5.5 and 7.3. In the urine of the patient pathological gamma heavy chain-protein was found only in a very low concentration. The predominant clinical symptom of the patient was a necrotizing vasculitis which became a therapeutical problem. In the immunofluorescence examination of the skin biopsy specimens, immunoglobulins and C3-complement could be detected in the stratum papillare. This fact would be compatible with the development of antibodies or immune complexes against deposited heavy-chain proteins. The arthropathy and the positive rheumatoid factor could similarly be explained by an immune complex mechanism.

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