Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: A simplified method

✍ Scribed by Giampaolo Bianchi; Giulio Marchesini; Hendrik Vilstrup; Andrea Fabbri; Maria Stella De Mitri; Marco Zoli; Emilo Pisiél

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 743 KB
• Volume: 13
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840130313

✦ Synopsis

The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has 50 f a r been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing a-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 2 7.0 L/hr to 18.4 2 6.7 Whr, p < 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a wellestablished, quantitative, liver function measure.

The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy. (HEPATOLOGY 199 1; 13:460-466.) Urea synthesis is a metabolic process occurring exclusively in the mitochondria and cytosol of hepatocytes. The process is driven by the plasma concentration of circulating amino acids (1). During amino acid infusion and after infusion (i.e., during increasing and decreasing amino acid concentrations), the relation of urea-N synthesis rate (UNSR) to mean blood concen-