A rapid method for determination of hepatic amino nitrogen to urea nitrogen conversion (‘the functional hepatic nitrogen clearance’)

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Abstract
The Functional Hepatic Nitrogen Clearance (FHNC) is a measure of the functional liver mass as to conversion of amino-N to urea-N. FHNC is the slope of the linear regression of multiple samples (10-20) of urea-N synthesis rates (UNSR) on blood a-amino-N concentrations (a-AN) during infusion of amino acids. UNSR is measured as urinary urea-N excretion rate corrected for accumulation in total body water (TBW) and loss in gut. A simplified method which estimate's FHNC from only two samples of UNSR and a-AN was developed. Urine was collected in two hourly intervals: before infusion of alanine, and from 2 to 3 h after start of alanine infusion. Blood-urea-N and a-amino-N was measured at the beginning and at the end of each urine sampling interval. TBW was estimated from a nomogram, and gut loss of urea was assigned a fixed value (14%). The two-sample FHNC was calculated as AUNSR (mmolh−1)/Amean a-AN (mmoll-1). Linear regression analysis of the two-sample estimates of FHNC on the ‘true’ multiple-sample values of FHNC in an independent population of control and cirrhotic subjects showed the two-sample estimates to be closely related with values of the multiple-sample method, the regression equation being: two-sample FHNC = -0.24+ 0.99 × multiple-sample FHNC, r2 = 0.98. A close relationship was also obtained when cirrhotic patients were considered alone: two-sample FHNC = 0.01 + 0.94 × multiple-sample FHNC, r2 = 0.98. The two-sample method also proved valid during changes in protein and carbohydrate supply which induces large but opposite changes in FHNC. The two-sample method gives reliable estimates of FHNC in both healthy and cirrhotic subjects and may prove valuable for investigation of hepatic N metabolism in larger populations.