Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate
Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted...
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| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/11/635 |
| _version_ | 1798000008700624896 |
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| author | Caroline C. Pelletier Mikael Croyal Lavinia Ene Audrey Aguesse Stephanie Billon-Crossouard Michel Krempf Sandrine Lemoine Fitsum Guebre-Egziabher Laurent Juillard Christophe O. Soulage |
| author_facet | Caroline C. Pelletier Mikael Croyal Lavinia Ene Audrey Aguesse Stephanie Billon-Crossouard Michel Krempf Sandrine Lemoine Fitsum Guebre-Egziabher Laurent Juillard Christophe O. Soulage |
| author_sort | Caroline C. Pelletier |
| collection | DOAJ |
| description | Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this study to explore renal excretion and mechanisms of accumulation of TMAO during CKD. We prospectively measured glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of trimethylamine (TMA), TMAO, choline, betaine, and carnitine by LC-MS/MS in 124 controls, CKD, and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a sub-group of 32 patients. Plasma TMAO was inversely correlated with mGFR (<i>r<sup>2</sup></i> = 0.388, <i>p</i> < 0.001), confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly different from mGFR, with a mean ± SD TMAO fractional excretion of 105% ± 32%. This suggests a complete renal excretion of TMAO by glomerular filtration with a negligible participation of tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively removed within 4 h of hemodiafiltration, showing a higher fractional reduction value than that of urea (84.9% ± 6.5% vs. 79.2% ± 5.7%, <i>p</i> = 0.04). This study reports a strong correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a decrease in TMAO glomerular filtration. Clearance data did not support a significant role for tubular secretion in TMAO renal elimination. |
| first_indexed | 2024-04-11T11:13:26Z |
| format | Article |
| id | doaj.art-eb7caf3cc35f426a9b614f4b8546e1d3 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T11:13:26Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-eb7caf3cc35f426a9b614f4b8546e1d32022-12-22T04:27:19ZengMDPI AGToxins2072-66512019-11-01111163510.3390/toxins11110635toxins11110635Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration RateCaroline C. Pelletier0Mikael Croyal1Lavinia Ene2Audrey Aguesse3Stephanie Billon-Crossouard4Michel Krempf5Sandrine Lemoine6Fitsum Guebre-Egziabher7Laurent Juillard8Christophe O. Soulage9Hospices Civils de Lyon, Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital E Herriot, F-69003 Lyon, FranceNUN, INRA, CHU Nantes, UMR 1280, PhAN, IMAD, CRNH-O, F-44000 Nantes, FranceHospices Civils de Lyon, Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital E Herriot, F-69003 Lyon, FranceNUN, INRA, CHU Nantes, UMR 1280, PhAN, IMAD, CRNH-O, F-44000 Nantes, FranceNUN, INRA, CHU Nantes, UMR 1280, PhAN, IMAD, CRNH-O, F-44000 Nantes, FranceNUN, INRA, CHU Nantes, UMR 1280, PhAN, IMAD, CRNH-O, F-44000 Nantes, FranceHospices Civils de Lyon, Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital E Herriot, F-69003 Lyon, FranceHospices Civils de Lyon, Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital E Herriot, F-69003 Lyon, FranceHospices Civils de Lyon, Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital E Herriot, F-69003 Lyon, FranceUniversité de Lyon, INSERM U1060, CarMeN, INSA de Lyon, Univ Lyon-1, F-69621 Villeurbanne, FranceGut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been reported to be strongly linked to renal function and to increased cardiovascular events in the general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data assessing renal handling of TMAO, we conducted this study to explore renal excretion and mechanisms of accumulation of TMAO during CKD. We prospectively measured glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of trimethylamine (TMA), TMAO, choline, betaine, and carnitine by LC-MS/MS in 124 controls, CKD, and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a sub-group of 32 patients. Plasma TMAO was inversely correlated with mGFR (<i>r<sup>2</sup></i> = 0.388, <i>p</i> < 0.001), confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly different from mGFR, with a mean ± SD TMAO fractional excretion of 105% ± 32%. This suggests a complete renal excretion of TMAO by glomerular filtration with a negligible participation of tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively removed within 4 h of hemodiafiltration, showing a higher fractional reduction value than that of urea (84.9% ± 6.5% vs. 79.2% ± 5.7%, <i>p</i> = 0.04). This study reports a strong correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a decrease in TMAO glomerular filtration. Clearance data did not support a significant role for tubular secretion in TMAO renal elimination.https://www.mdpi.com/2072-6651/11/11/635uremic toxintrimethylamine-n-oxiderenal clearancechronic kidney diseasehemodialysis |
| spellingShingle | Caroline C. Pelletier Mikael Croyal Lavinia Ene Audrey Aguesse Stephanie Billon-Crossouard Michel Krempf Sandrine Lemoine Fitsum Guebre-Egziabher Laurent Juillard Christophe O. Soulage Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate Toxins uremic toxin trimethylamine-n-oxide renal clearance chronic kidney disease hemodialysis |
| title | Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate |
| title_full | Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate |
| title_fullStr | Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate |
| title_full_unstemmed | Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate |
| title_short | Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate |
| title_sort | elevation of trimethylamine n oxide in chronic kidney disease contribution of decreased glomerular filtration rate |
| topic | uremic toxin trimethylamine-n-oxide renal clearance chronic kidney disease hemodialysis |
| url | https://www.mdpi.com/2072-6651/11/11/635 |
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