Volatile Organic Compounds in Uremia

Background

Although “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.

Methods

Breath 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.

Results

Breath 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.

Conclusion

Impairment 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.     

Physiological effects of Na+/Ca2+ exchanger knockdown by antisense oligodeoxynucleotides in arterial myocytes

Antisense oligodeoxynucleotides (AS-oligos) targeted to theNa⁺/Ca²⁺exchanger (NCX) inhibit NCX-mediatedCa²⁺ influx in mesenteric artery(MA) myocytes [Am. J. Physiol.269 (Cell Physiol. 38):C1340-C1345, 1995]. Here, we show AS-oligo knockdown ofNCX-mediated Ca²⁺ efflux. Ininitial experiments, the cytosolic freeCa²⁺ concentration([Ca²⁺]_cyt)was raised, and sarcoplasmic reticulum (SR)Ca²⁺ sequestration was blockedwith caffeine and cyclopiazonic acid; the extracellularNa⁺-dependent (NCX) component ofCa²⁺ efflux was then selectivelyinhibited in AS-oligo-treated cells but not in controls (no oligos ornonsense oligos). In contrast, theLa³⁺-sensitive (plasmalemmaCa²⁺ pump) component ofCa²⁺ efflux was unaffected inAS-oligo-treated cells. Knockdown of NCX activity was reversed byincubating AS-oligo-treated cells in normal media for 5 days. Transient[Ca²⁺]_cytelevations evoked by serotonin (5-HT) at 15-min intervals inAS-oligo-treated cells were indistinguishable from those in controls.When cells were stimulated every 3 min, however, the peak amplitudes ofthe second and third responses were larger, and[Ca²⁺]_cytreturned to baseline more slowly, in AS-oligo-treated cells than incontrols. Peak 5-HT-evoked responses in the controls, but notAS-oligo-treated cells, were augmented more than twofold inNa⁺-free media. This implies thatNCX is involved in Na⁺ gradientmodulation of SR Ca²⁺ stores andcell responsiveness. The repetitive stimulation data suggest that theNCX may be important during tonic activation of arterial myocytes.