MODEL-DERIVED ASSESSMENT OF UREA APPEARANCE IN RESPONSE TO ALANINE INFUSION - A QUANTITATIVE MEASURE OF LIVER-FUNCTION IN CIRRHOSIS

A three compartment mathematical model was used to analyse the urea response to an alanine infusion in six control subjects, and in 15 patients with liver cirrhosis and variable degree of hepatocellular failure. Model-derived coefficients were used to calculate two parameters (Y(max) and T(max)), able to describe the theoretical response of the conversion of amino acid derived nitrogen into urea, in response to a unit impulse in alanine concentration. They correspond to the maximum rate of conversion of nitrogen from an intermediary pool into urea and to the time delay between the impulse and Y(max), respectively. In cirrhosis, the apparent volume of distribution of infused alanine was smaller than in controls, while the conversion of alanine nitrogen into an intermediary pool of nitrogen and finally into urea nitrogen were both reduced. Also Y(max) was reduced by 50% in cirrhosis, whereas T(max) was increased by 50%, and both significantly correlated with galactose elimination capacity (GEC; R2 = 0.706 and R2 = 0.505, respectively) and with antipyrine clearance (Ap Cl; R2 = 0.823 and R2 = 0.576 respectively). Model-derived assessment of urea appearance in response to alanine infusion is able to quantify the functional liver cell mass, and may prove useful for the study of nitrogen metabolism in cirrhosis, mainly in relation to encephalopathy.