Urea synthesis by perfused rat liver in experimental uremia

Urea synthesis was examined in experimental uremia using the isolated perfused rat liver in order to assure strict control of substrate (NH4Cl) presented to the liver. Acute uremia was created in female Sprague-Dawley rats by bilateral nephrectomy (n = 7) 48 h prior to studies. Chronic uremia (8--14 weeks) was produced by right nephrectomy and segmental infarction of the left kidney in 7 rats. At infusion rates of NH4Cl (8.3 mumol/min) which resulted in prehepatic perfusate ammonia levels approximately twice the previously described Km value, livers of chronically uremic rats had slightly higher rates of urea production than controls (controls: 0.41 +/- 0.03; chronic uremia: 0.54 +/- 0.04 mumol/min/g of wet liver weight; p less than 0.02). In acute uremia, urea production was higher (0.66 +/- 0.05 mumol/min/g) than in sham-operated rats (0.59 +/- 0.05 mumol/min/g) but the differences did not achieve statistical significance. Simultaneously performed taurocholate transport studies did not reveal significant functional differences between the livers of uremic and control animals. The data suggest that urea production by livers of uremic rats is increased when compared to that of control animals.