Mechanism of Prominent Trimethylamine Oxide (TMAO) Accumulation in Hemodialysis Patients
| Autor: | Xin Hai, Thomas H. Hostetter, Mirela Dobre, Peter B. DeOreo, Veeda Landeras, Timothy W. Meyer |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Population lcsh:Medicine Excretion chemistry.chemical_compound Methylamines Renal Dialysis Internal medicine medicine Humans Urea lcsh:Science education Dialysis Volume of distribution Creatinine education.field_of_study Dialysis adequacy Multidisciplinary lcsh:R Endocrinology chemistry Case-Control Studies Kidney Failure Chronic lcsh:Q Female Hemodialysis Biomarkers Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 12, p e0143731 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Large size, protein binding and intracellular sequestration are well known to limit dialytic removal of compounds. In studying the normal renal and dialytic handling of trimethylamine oxide (TMAO), a molecule associated with cardiovascular disease in the general population, we discovered two largely unrecognized additional limitations to sustained reduction of a solute by chronic hemodialysis. We measured solute levels and handling in subjects on chronic hemodialysis (ESRD, n = 7) and compared these with levels and clearance in normal controls (NLS, n = 6). The ESRD patients had much higher peak predialysis plasma levels of TMAO than NLS (77 ± 26 vs 2±1 μM, mean ± SD, p0.05). However, TMAO has a volume of distribution about one half that of urea. Also in NLS the urinary clearance of TMAO was high (219±78 ml/min) compared to the urinary urea and creatinine clearances (55±14 and 119±21 ml/min, respectively). Thus, TMAO levels achieve multiples of normal much greater than those of urea due mainly to 1) TMAO's high clearance by the normal kidney relative to urea and 2) its smaller volume of distribution. Modelling suggests that only much more frequent dialysis would be required to lower levels Thus, additional strategies such as reducing production should be explored. Furthermore, using urea as the sole marker of dialysis adequacy may be misleading since a molecule, TMAO, that is dialyzed readily accumulates to much higher multiples of normal with urea based dialysis prescriptions. |
| Databáze: | OpenAIRE |
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