Excretion of Conjugated Bilirubin in the Isolated Perfused Rat Kidney

Abstract

1. Renal mechanisms of conjugated bilirubin excretion have been studied in isolated rat kidneys perfused with a protein-free dextran medium, containing conjugated bilirubin isolated from human bile. 2. In nine perfused kidneys with a low glomerular filtration rate (GFR) (<0·5 ml/min) and depressed tubular function, there was a significant linear correlation between conjugated bilirubin clearance and GFR (r = 0·97). 3. In contrast, nine kidneys with a normal GFR (> 0·8 ml/min) and good tubular function exhibited substantial tubular reabsorption of filtered conjugated bilirubin (mean 74%). Reabsorption was proportional to the filtered conjugated bilirubin load and a tubular transport maximum was not observed even at high concentrations (144 μmol/l). 4. The fractional reabsorption of bilirubin was unchanged by the addition of sodium aminohippurate to the medium. Perfusion with an albumin medium (10 g/l) resulted in a tenfold reduction in conjugated bilirubin clearance. 5. These observations indicate that non-protein-bound conjugated bilirubin is freely filtered by the glomeruli and then largely reabsorbed in the tubules. Evidence of tubular secretion was not obtained. 6. Chromatographic separation of bilirubin conjugates showed that the proportion of di- to monoconjugates in the urine was greater than in the perfusate. Whether this indicated further conjugation by the kidney of the monoconjugates or differential clearance of the conjugates was not established.