Kynurenine is a uremic toxin that is produced when a person has uremia or renal failure. Kynurenine is naturally synthesized in the body from tryptophan. Tryptophan is consumed through foods such as milk, eggs, chicken, turkey, and oats. Tryptophan is then transported from the small intestine into the blood by an amino acid transport. In the blood it travels to the liver and is transported into a hepatocyte by an amino acid transporter. The kynurenine pathway becomes dysregulated, potentially through over-stimulation by interferon gamma (IFNG). This hyperstimulation leads to large reductions in tryptophan levels as the indole dioxygenase (IDO) enzyme becomes more active. IDO activation results in the generation (from tryptophan) of large amounts of kynurenine (and its other metabolites) through a self-stimulating autocrine process. Kynurenine binds to the arylhydrocarbon receptor (AhR) found in most immune cells [5-7]. In addition to increased kynurenine production via IDO mediated synthesis, hyopalbuminemia can also lead to the release of bound kynurenine (and other immunosuppressive LysoPCs) into the bloodstream to fuel this kynurenine-mediated process. Regardless of the source of kynurenine, the kynurenine-bound AhR will migrate to the nucleus to bind to NF-kB which leads to more production of the IDO enzyme, which leads to more production of kynureneine and more loss of tryptophan. Kynurenine then enters the blood via a liver organic anion transporter such as solute carrier family 22 member 9. Kynurenine is shown to activate aryl hydrocarbon receptors that can lead to renal impairment, apoptosis, and kynurenine has also been found to disrupt the electron transport chain and oxidative phosphorylation causing muscle atrophy.

Metabolism and Physiological Effects of Kynurenine References