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-, pl ays an important role in acid-base homeostasis. This study measured urea sy nthesis rate (R-a urea) directly to assess its role in determining the acid -base status in patients with end-stage cirrhosis and after orthotopic live r transplantation (OLT). Cirrhotic patients were studied before surgery (n = 7) and on the second postoperative day(n = 11), using a 5-h primed-consta nt infusion of[N-15(2)]urea. Six healthy volunteers served as controls. R-a urea was 5.05 +/- 0.40 (SE) and 3.11 +/- 0.51 mu mol.kg(-1).min(-1), respe ctively, 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 cirrhoti c patients (not different). After OLT, R-a urea was 15.05 +/- 1.73 mu mol.k g(-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 do es not produce metabolic alkalosis. Concurrent postoperative metabolic alka losis and increased R-a urea indicate that the alkalosis is not caused by i mpaired R-a urea. It is consistent with, but does not prove, the concept th at the graft liver responds to metabolic alkalosis by augmenting R-a urea, thus increasing HCO3- consumption and moderating the severity of metabolic alkalosis produced elsewhere.