Back to Search
Start Over
The uremic toxin oxythiamine causes functional thiamine deficiency in end-stage renal disease by inhibiting transketolase activity.
- Source :
-
Kidney international [Kidney Int] 2016 Aug; Vol. 90 (2), pp. 396-403. Date of Electronic Publication: 2016 May 16. - Publication Year :
- 2016
-
Abstract
- Decreased transketolase activity is an unexplained characteristic of patients with end-stage renal disease and is linked to impaired metabolic and immune function. Here we describe the discovery of a link to impaired functional activity of thiamine pyrophosphate cofactor through the presence, accumulation, and pyrophosphorylation of the thiamine antimetabolite oxythiamine in renal failure. Plasma oxythiamine was significantly increased by 4-fold in patients receiving continuous ambulatory peritoneal dialysis and 15-fold in patients receiving hemodialysis immediately before the dialysis session (healthy individuals, 0.18 [0.11-0.22] nM); continuous ambulatory peritoneal dialysis patients, 0.64 [0.48-0.94] nM; and hemodialysis patients (2.73 [1.52-5.76] nM). Oxythiamine was converted to the transketolase inhibitor oxythiamine pyrophosphate. The red blood cell oxythiamine pyrophosphate concentration was significantly increased by 4-fold in hemodialysis (healthy individuals, 15.9 nM and hemodialysis patients, 66.1 nM). This accounted for the significant concomitant 41% loss of transketolase activity (mU/mg hemoglobin) from 0.410 in healthy individuals to 0.240 in hemodialysis patients. This may be corrected by displacement with excess thiamine pyrophosphate and explain lifting of decreased transketolase activity by high-dose thiamine supplementation in previous studies. Oxythiamine is likely of dietary origin through cooking of acidic thiamine-containing foods. Experimentally, trace levels of oxythiamine were not formed from thiamine degradation under physiologic conditions but rather under acidic conditions at 100(°)C. Thus, monitoring of the plasma oxythiamine concentration in renal failure and implementation of high-dose thiamine supplements to counter it may help improve the clinical outcome of patients with renal failure.<br /> (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Diet adverse effects
Female
Humans
Kidney Failure, Chronic blood
Kidney Failure, Chronic therapy
Male
Middle Aged
Oxythiamine blood
Oxythiamine metabolism
Protein Processing, Post-Translational
Renal Dialysis
Renal Elimination
Thiamin Pyrophosphokinase metabolism
Thiamine therapeutic use
Thiamine Deficiency drug therapy
Vitamin B Complex therapeutic use
Antimetabolites toxicity
Kidney Failure, Chronic metabolism
Oxythiamine toxicity
Thiamine Deficiency chemically induced
Thiamine Pyrophosphate metabolism
Transketolase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 90
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 27198804
- Full Text :
- https://doi.org/10.1016/j.kint.2016.03.010