Abstract
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.
Highlights
In patients with end-stage chronic kidney disease (CKD) a "uremic fetor" is frequently noted and has been assigned mainly to exhalation of ammonia, dimethylamine and trimethylamine [1]
Several studies on the breath profile of volatile organic compounds (VOCs) have been performed with adults on hemodialysis [2,3,4,5,6,7] and evidence was obtained that the breath profile is already affected as renal function is only mildly impaired [5]
As kidney dysfunctions lead to an impaired removal of waste products from the blood, urea and creatinine among others are metabolized to ammonia
Summary
In patients with end-stage chronic kidney disease (CKD) a "uremic fetor" is frequently noted and has been assigned mainly to exhalation of ammonia, dimethylamine and trimethylamine [1]. Several studies on the breath profile of volatile organic compounds (VOCs) have been performed with adults on hemodialysis [2,3,4,5,6,7] and evidence was obtained that the breath profile is already affected as renal function is only mildly impaired [5]. Excess ammonia as well as nitrogen-containing volatile compounds like methylamines can diffuse into the lungs and are shown in higher concentrations in breath of end-stage CKD patients in comparison to healthy controls [4,8]. Exhaled isoprene concentrations were higher after hemodialysis [2,3,8]
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