Effect of liver disease and transplantation on urea synthesis in humans: relationship to acid-base status

Abstract

It has been suggested that hepatic urea synthesis, which consumes[Formula: see text], plays an important role in acid-base homeostasis. This study measured urea synthesis rate (Raurea) directly to assess its role in determining the acid-base status in patients with end-stage cirrhosis and after orthotopic liver transplantation (OLT). Cirrhotic patients were studied before surgery ( n = 7) and on the second postoperative day ( n = 11), using a 5-h primed-constant infusion of [15N2]urea. Six healthy volunteers served as controls. Raurea was 5.05 ± 0.40 (SE) and 3.11 ± 0.51 μmol ⋅ kg−1⋅ min−1, respectively, in controls and patients with cirrhosis ( P < 0.05). Arterial base excess was 0.6 ± 0.3 meq/l in controls and −1.1 ± 1.3 meq/l in cirrhotic patients (not different). After OLT, Raurea was 15.05 ± 1.73 μmol ⋅ kg−1⋅ min−1, which accompanied an arterial base excess of 7.0 ± 0.3 meq/l ( P < 0.001). We conclude that impaired Raurea in cirrhotic patients does not produce metabolic alkalosis. Concurrent postoperative metabolic alkalosis and increased Raurea indicate that the alkalosis is not caused by impaired Raurea. It is consistent with, but does not prove, the concept that the graft liver responds to metabolic alkalosis by augmenting Raurea, thus increasing[Formula: see text] consumption and moderating the severity of metabolic alkalosis produced elsewhere.