Urinary excretion of bile acids in cholestasis: evidence for renal tubular secretion in man

1. The apparent renal clearance of intravenously injected [14C]glycocholate and [3H]chenodeoxycholate-3-sulphate was estimated in 22 patients with cholestasis. The degree of protein binding of the isotopes in serum from these patients was determined. The effects of pharmacological agents, changes in urine flow rate and pH on renal clearance was studied. 2. The mean renal clearance of [14C]glycocholate was 1 . 7 +/- 0 . 4 ml/min (mean +/- SEM), and that of [3H]chenodeoxycholate-3-sulphate was 6 . 4 +/- 0 . 9 ml/min. [14C]Glycocholate was 80 . 1% protein bound and [3H]chenodeoxycholate-3-sulphate 96 . 5% protein bound. 3. Comparisons of the observed clearance rates with those calculated on the basis of glomerular filtration of the unbound fraction suggest that whereas [14C]glycocholate is predominantly reabsorbed by the renal tubules, [3H]chenodeoxycholate-3-sulphate appears in the urine mainly as the result of tubular secretion. 4. Probenecid, ethacrynic acid, frusemide and bendrofluazide decreased the clearance of both bile acids, implying competition for secretion via the proximal tubular organic acid secretory pathway between these compounds and bile acids. 5. Passive non-ionic diffusion does not seem to be an important mechanism in the renal excretion of bile acids as changes in urine flow rate and pH did not influence bile acid clearance. 6. A greater affinity of the proximal tubular organic acid secretory pathway for sulphated than for non-sulphated bile acids may explain the higher observed renal clearance rate of sulphated bile acids.