Gases as Uremic Toxins: Is There Something in the Air?

Abstract

Summary: The field of uremic toxicity comprises the study of a large number of different substances, classified in relation to various characteristics, for example, protein-binding, dimensions, and so forth. The endogenous compounds of a gaseous nature have received much attention lately from the scientific community because of their increasingly recognized importance in health and disease. Among these substances, some are uremic toxins per se, others are related to uremic toxins, or can become toxic under some circumstances. We divided them into two broad categories: organic and inorganic compounds. Among the organic compounds are phenols, indols, 2-methoxyresorcinol, p-hydroxy hippuric acid and phenyl acetic acid, trimethylamine, and dimethylamine; among the inorganic solutes are ammonia, nitric oxide, carbon monoxide, and hydrogen sulfide. In this article, these substances are described in relation to the elements that they affect or by which they are affected in uremia, which are the blood, breath, stools, and the gastrointestinal tract. In addition, the effect of the dialysis procedure on exhaled gases are described. Semin Nephrol 34:135-150 C 2014 Published by Elsevier Inc.

Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease

“…H 2 S is also significantly lower in plasma from CKD and hemodialysis patients compared to controls, while the metabolic related compounds cystathione, homolanthionine and lanthionine are significantly increased [58]. In this respect, lanthionine, a byproduct of the transsulfuration pathway found to be quite high in the plasma of CKD patients, is able to exert several toxic effects [59][60][61][62]. Lanthionine is also an end product of bacterial metabolism.…”

Urea, a true uremic toxin: the empire strikes back

“…Firstly, urea diffuses from the blood into the gut lumen and is metabolized by gut bacterial urease to ammonia [CO(NH 2 ) 2 + H 2 O → CO 2 + 2NH 3 ]; the latter is hydrolysed into caustic ammonium hydroxide [NH 3 + H 2 O → NH 4 OH] which is capable of dissolving proteins [39,40]. Although breath ammonia is elevated in ESRD patients [41,42] due to microbial conversion of urea in the gastrointestinal tract and the oral cavity [43,44], abnormal systemic ammonia levels have not been reported in CKD. In vitro, confluent cultured human colonocytes exposed to media containing urea at clinically relevant concentrations 42 or 74 mg/dl show a concentrationdependent fall in trans-epithelial electrical resistance and loss of tight junction proteins [40].…”

Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease

“…11 Several other uremic toxins also originate from bacterial metabolization in the gut, such as hippuric acid, phenyl sulfate, trimethylamine-N-oxide, and hydrogen sulfide. 11,13,18,19 In blood, PBUTs reversibly bind to different degrees on plasma albumin. 20 In CKD, removal of the free (glomerular filtration) as well as the bound (tubular secretion) fraction of uremic toxins is impaired, resulting in their accumulation in blood.…”