Title
Guanidino compounds as uremic (neuro)toxinsGuanidino compounds as uremic (neuro)toxins
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Neurochemistry and behaviour
Publication type
article
Publication
Baltimore, Md,
Subject
Human medicine
Source (journal)
Seminars in dialysis. - Baltimore, Md
Volume/pages
22(2009):4, p. 340-345
ISSN
0894-0959
ISI
000269263600005
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Neurological and vascular impairment are important sources of morbidity in patients with renal failure. A portion of patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in chronic renal failure patients, even in those otherwise adequately dialyzed. Epileptic and cognitive symptoms are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be substantially increased as well in serum, cerebrospinal fluid, and brain of uremic patients. These compounds, "uremic" GCs, are creatinine, guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine. All four compounds are experimental convulsants in concentrations similar to those found in uremic brain. We described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. It was demonstrated that the excitatory effects of uremic GCs on the central nervous system can be explained by the activation of N-methyl-d-aspartate receptors by GSA, concomitant inhibition of ã-aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy. In this article, we review the uremic GCs with particular attention to their neurotoxicity. We elaborate in detail on the mechanisms of action of the neurotoxic uremic GCs and summarize the kinetics of these toxins.
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