Increased hepatic urea synthesis in patients with active inflammatory bowel disease

Abstract

Background/Methods: Patients with active inflammatory bowel disease are often reported to be in negative nitrogen balance. Therefore, we examined basal and amino acid stimulated urea synthesis in 11 patients with active inflammatory bowel disease (six with Crohn's disease and five with ulcerative colitis) and in 10 patients with non-active disease (six with Crohn's disease and four with ulcerative colitis). A primed continuous infusion of an amino acid mixture was given from t=1 h to t=5 h; during the first and the last 2 h no amino acid infusion was given. Urea nitrogen synthesis rate was calculated in hourly intervals for 7 consecutive hours. Urea nitrogen synthesis rate was quantified independent of changes in blood amino acid concentration by means of the functional hepatic nitrogen clearance, i.e. the linear slope of the regression of urea nitrogen synthesis rate on blood amino acid concentration. Results: Basal urea nitrogen synthesis rate was 24.5±2.9 mmol/h in the patients with no disease activity and 43.8±2.2 mmol/h in patients with active disease ( p<0.01). During amino acid infusion urea nitrogen synthesis rate was elevated two-fold in the patients with active disease. Functional hepatic nitrogen clearance was 28.2±1.5 l/h in patients with no disease activity and 56.1±4.1 l/h in patients with active disease ( p<0.01). No differences between the two groups were observed as regards basal or stimulated plasma glucagon and cortisol and serum levels of interleukin-1α, interleukin-1β, tumor necrosis factor plasma and interleukin-6. Conclusions: The results show that the liver function related to conversion of amino-nitrogen to urea is increased in patients with active inflammatory bowel disease. No differences among known and possible regulators of urea synthesis were found between the two groups. The accelerated hepatic amino-nitrogen conversion contributes to the less efficient nitrogen economy in patients with active inflammatory bowel disease.