Exhaled volatile substances mirror clinical conditions in pediatric chronic kidney disease

<div><p>Monitoring metabolic adaptation to chronic kidney disease (CKD) early in the time course of the disease is challenging. As a non-invasive technique, analysis of exhaled breath profiles is especially attractive in children. Up to now, no reports on breath profiles in this patient cohort are available. 116 pediatric subjects suffering from mild-to-moderate CKD (n = 48) or having a functional renal transplant KTx (n = 8) and healthy controls (n = 60) matched for age and sex were investigated. Non-invasive quantitative analysis of exhaled breath profiles by means of a highly sensitive online mass spectrometric technique (PTR-ToF) was used. CKD stage, the underlying renal disease (HUS; glomerular diseases; abnormalities of kidney and urinary tract or polycystic kidney disease) and the presence of a functional renal transplant were considered as classifiers. Exhaled volatile organic compound (VOC) patterns differed between CKD/ KTx patients and healthy children. Amounts of ammonia, ethanol, isoprene, pentanal and heptanal were higher in patients compared to healthy controls (556, 146, 70.5, 9.3, and 5.4 ppbV vs. 284, 82.4, 49.6, 5.30, and 2.78 ppbV). Methylamine concentrations were lower in the patient group (6.5 vs 10.1 ppbV). These concentration differences were most pronounced in HUS and kidney transplanted patients. When patients were grouped with respect to degree of renal failure these differences could still be detected. Ammonia accumulated already in CKD stage 1, whereas alterations of isoprene (linked to cholesterol metabolism), pentanal and heptanal (linked to oxidative stress) concentrations were detectable in the breath of patients with CKD stage 2 to 4. Only weak associations between serum creatinine and exhaled VOCs were noted. Non-invasive breath testing may help to understand basic mechanisms and metabolic adaptation accompanying progression of CKD. Our results support the current notion that metabolic adaptation occurs early during the time course of CKD.</p></div

Exhaled alveolar concentrations of isoprene relative to the BMI in controls (blue circles) and patients (red circles).

<p>Controls (n = 60): r = 0.53, p < 0.001; patients (n = 56): r = 0.47, p<0.001.</p

Clinical characteristics of patients.

<p>Data is given as median and range. Superscripts denote significant differences between identically labelled groups.</p

Anthropometric data of the study population and relevant medications in CKD patients.

<p>Anthropometric data of the study population and relevant medications in CKD patients.</p

Schematic description of continuous real-time breath analysis.

<p>a) Participants breathed through a sterile mouthpiece without resistance. Ex- and inhaled breath was transferred continuously into the heated transfer line (connected via t-piece) of the PTR-ToF-MS in a side-stream mode at a flow of 20 ml/min. b) Every 200 ms a TOF—mass spectrum was recorded. c) Profiles of breath VOCs could be recorded continuously and in a phase resolved way. Acetone (red curve 59.049 m/z—as endogenous, blood borne VOC) was used to track breath phases and to assign all other mass traces to alveolar (red areas) and inhalation (blue areas) phases. In this way, intensities of VOCs other than acetone, such as isoprene (pink curve, 69.070 m/z) or dimethyl sulfide (blue curve, 63.026 m/z) could be assigned to the different breath phases and quantified in alveolar and inspiratory air.</p

Exhaled alveolar concentrations of ammonia, ethanol, methylamine, isoprene, pentanal and heptanal relative to the eGFR in CKD patients (n = 56).

<p>Exhaled alveolar concentrations of ammonia, ethanol, methylamine, isoprene, pentanal and heptanal relative to the eGFR in CKD patients (n = 56).</p

Exhaled alveolar concentrations of selected VOC in the study population.

<p>Exhaled alveolar concentrations of selected VOC in the study population.</p

Heat map (A) and PCA score (B) obtained in CKD patients (n = 56) and controls (n = 60).

<p>A: Heat map based on normalized data of 71 mass traces (18 to 373 m/z) in breath of CKD patients (left) and healthy controls (right). Regions with elevated breath VOC levels are shown as red and yellow boxes for patients and controls, respectively. B: PCA score plot (PC-1 vs. PC-2) of healthy controls (blue squares, n = 60) and CKD patients (red dots, n = 56). Red circles represent data from patients with a functional renal transplant.</p

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

11 novembre 19001900/11/11 (A1,N27)

Continuous Real Time Breath Gas Monitoring in the Clinical Environment by Proton-Transfer-Reaction-Time-of-Flight-Mass Spectrometry

Analysis of volatile organic compounds (VOCs) in breath holds great promise for noninvasive diagnostic applications. However, concentrations of VOCs in breath may change quickly, and actual and previous uptakes of exogenous substances, especially in the clinical environment, represent crucial issues. We therefore adapted proton-transfer-reaction-time-of-flight-mass spectrometry for real time breath analysis in the clinical environment. For reasons of medical safety, a 6 m long heated silcosteel transfer line connected to a sterile mouth piece was used for breath sampling from spontaneously breathing volunteers and mechanically ventilated patients. A time resolution of 200 ms was applied. Breath from mechanically ventilated patients was analyzed immediately after cardiac surgery. Breath from 32 members of staff was analyzed in the post anesthetic care unit (PACU). In parallel, room air was measured continuously over 7 days. Detection limits for breath-resolved real time measurements were in the high pptV/low ppbV range. Assignment of signals to alveolar or inspiratory phases was done automatically by a matlab-based algorithm. Quickly and abruptly occurring changes of patients’ clinical status could be monitored in terms of breath-to-breath variations of VOC (e.g. isoprene) concentrations. In the PACU, room air concentrations mirrored occupancy. Exhaled concentrations of sevoflurane strongly depended on background concentrations in all participants. In combination with an optimized inlet system, the high time and mass resolution of PTR-ToF-MS provides optimal conditions to trace quick changes of breath VOC profiles and to assess effects from the clinical environment