title: To pee or not to pee: ammonia hypothesis of hepatic encephalopathy revisited.
abstract: Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver failure. Its aetiology has been debated for the past 100 years. Nevertheless, elevated ammonia levels are still believed to play a central role in its pathogenesis. After intestinal production, ammonia is detoxified by the liver. In liver failure, skeletal muscle and brain have been proposed to be alternative, although temporary, ammonia detoxifying organs. However, there is an increasing body of evidence that the kidney, in addition to the gut, is a pivotal organ determining systemic ammonia levels. In the last 20 years, it has been shown that the kidney can switch from an organ of systemic net ammonia production to a net ammonia excretion organ. The kidney plays a central role in the determination of ammonia levels. It is at least as important as the gut and could therefore serve as a target for new treatments for hepatic encephalopathy.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, and School of Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: Liliane
authors.initials: L
authors.lastname: Mpabanzi
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: Marcel C G
authors.initials: MC
authors.lastname: van de Poll
authors.forename: Peter B
authors.initials: PB
authors.lastname: Soeters
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.forename: Cees H C
authors.initials: CH
authors.lastname: Dejong
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D017093:Liver Failure / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D012307:Risk Factors; D015854:Up-Regulation; D014554:Urination
chemical_list: D000641:Ammonia