No evidence is available on the transport of biliary biliary route) may be increased in certain pathological urate and the possible role of choleretic agents in the conditions such as uremia. 2,3 In addition, several facregulation of biliary urate elimination in humans. To tors such as extracellular fluid volume, urine flow rate, test this hypothesis we studied the following: (1) 45 choalcohol, food components, many medications (mainly lecystomized patients to determine urate levels in hepyrazinamide and probenecid), and hormones alter patic bile and gallbladder bile, and (2) 13 cholecystourate kidney transport. 4 Assuming that the physiologimized patients fitted with T-tubes to determine the cal processes of bile secretion and urine excretion share effects of secretin injection (either 70 U of porcine secremany similarities, biliary urate transport may be moditin or 0.02 mgrkg 01 of synthetic human secretin, as a fied in the same way as urate filtered in the glomerulus single dose) and/or mannitol infusion (5 cm 3 rmin 01 for 90 is altered during its passage through the renal tubules. minutes) on biliary urate excretion. In the latter group, samples of bile and serum were analyzed for urate under According to the widely accepted ''four component basal state and after the administration of both agents. model,'' tubular phases that modulate renal urate ex-In our first approach, results showed that urate concencretion in normal subjects are as follows 5 : (1) nearly trations present in hepatic as well as in gallbladder bile free filtration at the glomerulus; (2) almost complete were much lower than the corresponding values in sereabsorption (99%) 6 at a site proximal to the tubular rum (P Γ΅ .001). The mean gallbladder bile urate concenlocation of urate secretion; (3) tubular secretion that tration was not significantly increased over the concenrepresents 40% of filtered urate in normouricemic tration in hepatic bile. When compared with basal state states; and (4) postsecretory reabsorption of about values, porcine and synthetic secretin induced a signifithree quarters of the secreted amount. Thus, urinary cant increase in mean urate clearance (P Γ΅ .001) because
urate comes mainly from secreted compound, the filof a significant increase in mean bile flow (P Γ΅ .001), whereas the mean biliary urate concentration signifi-tered urate representing a percentage of less than 10% cantly decreased (P Γ΅ .001) with a concomitant decrease of the excreted amount. 6 On the other hand, the biliary in the mean serum urate concentration (P Γ΅ .02). Mannitransport of urate has not, to our knowledge, been pretol also induced a significant increase in the mean urate viously investigated. In view of the fact that extrarenal clearance (P Γ΅ .002) because of a significant increase in urate elimination (including the biliary elimination the mean biliary urate concentration (P Γ΅ .01) with a route) may be important in some of the previously menconcomitant decrease in the mean serum urate concentioned pathological conditions, we sought to investigate tration (P Γ΅ .01) and without changes in the mean bile the biliary urate clearance (1) under basal conditions flow (P ΓΊ .05). Therefore, it appears that a substantial and (2) after administration of secretin and mannitol,
of urate is eliminated by biliary route. The load which represent standard approaches in canalicular of biliary urate excreted may be modified by mannitol and secretin and possibly other factors, a finding that and ductular bile flow measurements in patients with could have an application in some pathological condicomplete biliary drainage. tions associated with decreased renal urate excretion. PATIENTS AND METHODS (HEPATOLOGY 1996;23:229-233.) Patients and Study Design. After informed consent was Uric acid, the end product of purine degradation in obtained from the Ethical Committee of the University of humans, is mainly excreted (about two thirds of the Thessaloniki, the following three groups of patients were studied: groups 1, 2, and 3. Group 1 consisted of 30 patients (4 body's pool) by the kidneys. 1 The remaining proportion men and 26 women; age range, 24-82 years) who underwent of the substance excreted by other routes (including the elective cholecystectomy for symptomatic gallstone disease. Gallbladder bile and blood samples of these patients were From the Department of Medicine, Second Medical Unit, Aristotelian Uniobtained after a standard open cholecystectomy for measureversity of Thessaloniki, 54642 Thessaloniki, Greece.
ments of urate and bile acids concentrations. Group 2 con-