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High levels of phenylacetylglutamine in the urine following metabolism by the gut microbiota may also indicate early renal decline associated with kidney dysfunction and chronic kidney disease (CKD). In CKD, phenylacetylglutamine is considered a uremic toxin which is taken up, circulated and retained in the blood after microbial fermentation of certain proteins and amino acids in the gut. Blood serum levels of phenylacetylglutamine in CKD are used as a mortality determinant. Blood plasma levels of phenylacetylglutamine increase with exposure to cigarette smoke, in patients with ischemic heart failure, with cardiovascular risk or hypertension, in the development of renal disease, and in patients with type 2 diabetes.