Urea Synthesis After Protein Feeding Reflects Hepatic Mass in Rats

Urea synthesis is an exclusive biosynthetic function of the liver. Since the exact relationship between urea synthesis in vivo and functional liver mass remains unclear, we established an animal model using oral protein loading and measurement of resultant urea synthesis in rats. We studied rats subjected to sham operation, 40% hepatectomy, 66% hepatectomy, portacaval shunt and CC1₄‐induced cirrhosis. Urea synthesis was calculated as the sum of urinary urea excretion and accumulation of urea in body water during the 6‐hr period after oral administration of a casein protein load equivalent to 20 gm per kg body weight. Peak urea synthesis rate in the sham‐operated group of rats was 142 ± 11 μmoles per hr per gm wet liver weight (mean ± 1 S.D.), 473 ± 34 μmoles per hr per gm liver protein and 80 ± 5 μmoles per hr per mg liver DNA. This rate closely matched those of the other groups for each type of liver mass measurement. Marked reduction (p < 0.01) of urea synthesis on a DNA basis was noted only in the CCl₄‐cirrhotic livers, related to the significantly higher (p < 0.01) DNA content of the cirrhotic livers. Similarly, increased (p < 0.05) liver protein content of the sham‐operated rats when compared with the other groups was reflected in slightly lower urea synthesis rates expressed on the basis of liver protein (p < 0.05) when compared to that of all other groups. The slopes of the trend lines which define the relationship of urea synthesis rates in each group to total liver mass (liver weight, protein content and DNA content) were not significantly different. We conclude that urea synthesis rates after oral administration of a protein load reflect liver mass in terms of wet weight, liver protein content and liver DNA content. This relationship remains valid in the presence of changes in liver parenchymal mass, portacaval shunting and CC1₄‐cirrhosis.