PURINE METABOLISM IN PATIENTS WITH GOUT - THE ROLE OF LEAD

Primary gout is characterized by increased plasma and decreased urinar y concentrations of hypoxanthine, xanthine and uric acid. To examine w hether lead could explain the disturbance of purine metabolism in gout , we determined hypoxanthine, xanthine and uric acid metabolism and 5- day cumulative urinary lead excretion rates after an EDTA (calcium dis odium edetate) test in 27 patients with primary gout and reduced creat inine clearance (C-cr) and in 50 patients with gout and normal C-cr. T he results were compared to those obtained in 26 normal subjects match ed for age. All gout patients evidenced a marked renal underexcretion of hypoxanthine, xanthine and uric acid relative to their increased pl asma levels. Purine metabolism was remarkably similar in both gout gro ups except for a significantly lower uric acid excretion in patients w ith reduced C-cr. Blood lead levels and cumulative lead excretion rate s were significantly higher in gout patients with renal failure as com pared to patients with normal C-cr. Fourteen patients (52%) with renal insufficiency and 6 (12%) with normal C-cr showed increased lead excr etion rates (95% Cl for the difference, 29-51%, p < 0.001). Mobilizabl e lead was not significantly correlated with serum or urinary purine c oncentrations. Hypoxanthine, xanthine and uric acid underexcretion was similar in gout patients with increased or normal cumulative lead exc retion rates. The prevalence of atheromatosis and arterial hypertensio n together was significantly higher in gout patients with renal failur e than in patients with normal C-cr (81 vs. 60%, 95% Cl for the differ ence, 11-31%, p < 0.005). These results indicate that lead is not a si gnificant contributor to the renal underexcretion of purines in gout. An increased mobilizable lead is not by itself evidence that lead is t he cause of the renal insufficiency in patients with primary gout. Ath eromatous nephropathy and/or nephroangiosclerosis may explain impaired renal function in patients with primary gout.