Volatile Organic Compounds in Uremia

Abstract

BackgroundAlthough “uremic fetor” has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia.MethodsBreath analysis was performed in 28 adults with an eGFR ≥60 ml/min per 1.73 m2, 26 adults with chronic renal failure corresponding to an eGFR of 10–59 ml/min per 1.73 m2, and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry.ResultsBreath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10–59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis.ConclusionImpairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules.

Detection of Volatile Malodorous Compounds in Breath: Current Analytical Techniques and Implications in Human Disease

“…A recent study by Pagonas et al employs IMS coupled to a MCC, to identify specific VOC in patients with ESRD before and after hemodialysis [128]. Several compounds such as ammonia, hydroxyacetone and 3-hydroxybutanone, were significantly increased in ESRD patients as opposed to healthy volunteers.…”

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

“…10,14 A recent study showed that ammonia concentrations in the breath also are increased in chronic renal failure not requiring dialysis. 18 In 1977, Simenhoff et al 17 already found that, apart from ammonia, trimethylamine (TMA) and dimethylamine (DMA) underlie the fishy odor in uremia. TMA and DMA are aliphatic amines, boiling between -61C and -71C, thus being highly volatile.…”

“…It confirmed the findings on ammonia and DMA/TMA as described earlier. 18 Moreover, the study showed that 3-hydroxy-2-butanone (acetoin) and hydroxyacetone accumulated with decreasing renal function and were eliminated by dialysis. 3-Hydroxy-2-butanone is an organic compound generated primarily by bacteria and plants.…”

“…Independently from its origin, the data of the earlier-mentioned study suggest a renal elimination. 18 In contrast to acetone, there are no data on hydroxyacetone in human blood or breath available. Acetone accumulates in the breath in diabetic ketoacidosis and liver disease.…”

“…38 In analogy to 4-heptanone, 4-heptanal and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis as well. 18 The question arises of why the analysis of exhaled VOCs has not been used as a clinical diagnostic tool thus far, although uremic fetor has long been believed to be characteristic of renal failure. There are two obvious reasons.…”