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

It has been suggested that hepatic urea synthesis, which consumes HCO₃/^-, plays an important role in acid-base homeostasis. This study measured urea synthesis rate (R(a) urea) 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. R(a) urea 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, R(a) urea 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 R(a) urea in cirrhotic patients does not produce metabolic alkalosis. Concurrent postoperative metabolic alkalosis and increased R(a) urea indicate that the alkalosis is not caused by impaired R(a) urea. It is consistent with, but does not prove, the concept that the graft liver responds to metabolic alkalosis by augmenting R(a) urea, thus increasing HCO^-₃ consumption and moderating the severity of metabolic alkalosis produced elsewhere.