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Open AccessArticle

Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate

1
Hospices Civils de Lyon, Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital E Herriot, F-69003 Lyon, France
2
Université de Lyon, INSERM U1060, CarMeN, INSA de Lyon, Univ Lyon-1, F-69621 Villeurbanne, France
3
NUN, INRA, CHU Nantes, UMR 1280, PhAN, IMAD, CRNH-O, F-44000 Nantes, France
4
CRNH-O Mass Spectrometry Core Facility, F-44000 Nantes, France
5
ELSAN, clinique Bretéché, F-44000 Nantes, France
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(11), 635; https://doi.org/10.3390/toxins11110635
Received: 27 September 2019 / Revised: 21 October 2019 / Accepted: 30 October 2019 / Published: 1 November 2019
(This article belongs to the Section Uremic Toxins)
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 (r2 = 0.388, p < 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%, p = 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. View Full-Text
Keywords: uremic toxin; Trimethylamine-N-oxide; renal clearance; chronic kidney disease; hemodialysis uremic toxin; Trimethylamine-N-oxide; renal clearance; chronic kidney disease; hemodialysis
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Pelletier, C.C.; Croyal, M.; Ene, L.; Aguesse, A.; Billon-Crossouard, S.; Krempf, M.; Lemoine, S.; Guebre-Egziabher, F.; Juillard, L.; Soulage, C.O. Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate. Toxins 2019, 11, 635.

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