High plasma arginine concentrations in critically ill patients suffering from hepatic failure

Abstract

Objective: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothesized high arginine plasma concentrations in critically ill patients suffering from hepatic failure. Design: We prospectively collected blood samples from a cross-section of intensive care unit patients. Setting: Surgical intensive care unit of a Dutch university medical center. Subjects: A total of 52 critically ill patients with clinical evidence of dysfunction of more than two organs were recruited. Measurements: Plasma arginine concentrations were determined by HPLC. We identified correlations of arginine concentrations with organ failure scores and laboratory variables by univariate and multiple regression analyses. Results: High plasma arginine concentrations were found in critically ill patients developing organ failure. Patients who were in the highest quartile of plasma arginine concentrations had significantly lower fibrinogen concentrations, higher lactic acid concentrations, and longer prothrombin time. Stepwise multiple regression analysis showed that concentrations of arginine were independently associated with the presence of hepatic failure (P ¼ 0.03) and renal failure (P ¼ 0.048). In addition, lactic acid proved to be an independent determinant of plasma arginine concentration (P ¼ 0.014). Conclusions: Critically ill patients who suffer from hepatic failure have elevated plasma arginine concentrations. Additional arginine in the treatment of these patients can be harmful, and therefore should not be used as a standard nutritional regimen until further evaluation.

Sequential change of asymmetric dimethylarginine levels after initiation of peritoneal dialysis in patients with end‐stage renal disease

“…Approximately 300 µmol of ADMA is generated per day from various types of cells in the adult 13,14 . Particularly, hepatocytes provide a major contribution to the regulation of circulating ADMA, 15 taking up large amounts of arginine from the hepatic blood flow; 16 some of these compounds are metabolized by aminotransferase in the hepatocytes 17 . There is evidence that L‐arginine inhibits the metabolism of ADMA in a dose‐dependent manner in the hepatocyte by competing for DDAH enzyme activity, causing increased intracellular and plasma ADMA levels 18,19 .…”

Arginine Enriched Nutrition in Trauma Patients

“…The addition of nutrients to critically ill patients to further enhance the immune system seems therefore unlogical and may even be harmful. Moreover, in critically ill patients with hepatic dysfunction we measured highly elevated plasma concentrations of arginine [36]. Again, dietary enrichment with arginine in the treatment of these patients seems to be unnecessary.…”

“…However, more research is needed to identify possible harmful effects of arginine and other nutrients in subgroups of critically ill patients that might be jeopardised by arginine supplementation. In addition to patient populations who are in a hyperinflammatory state (e. g., sepsis), another group that probably will not benefit from additional arginine is the critically ill patient who already has high arginine plasma levels, such as in hepatic failure [36]. Alternatively, the administration of glutamine may be beneficial in these patients.…”

Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

“…Hepatocytes take up large amounts of l -arginine from the hepatic circulation, and liver dysfunction is associated with high plasma l -arginine levels [32]. Although fractional extraction of ADMA is slightly higher in the kidney than in the liver, the liver clears more ADMA from the circulation than the kidney because it has a higher total plasma flow [33].…”