PROGRESS IN UREMIC TOXIN RESEARCH: Guanidino Compounds as Uremic (Neuro)Toxins
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 γ‐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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Uraemic guanidino compounds with neuroexcitatory effects are found in brain regions responsible for cognition (thalamus and mammillary bodies) in patients with chronic kidney disease.
“Uraemic guanidino compounds with neuroexcitatory effects have been found in brain regions responsible for cognition (thalamus and mammillary bodies) in patients with CKD182”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [182]
The presence of uraemic guanidino compounds in cognition-related brain regions suggests a direct role of these compounds in cognitive impairment in chronic kidney disease.
“suggesting a direct role of these compounds in cognitive impairment.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [182]
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The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
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- Authors
- De Deyn, P. P., Vanholder, R., Eloot, S., & Glorieux, G.
- Affiliations
- Ghent University Hospital (BE)
- Venue
- Seminars in Dialysis
- Publisher
- Wiley
- Published
- 2009-07
- Volume
- 22
- Issue
- 4
- Pages
- 340-345
- ISSN
- 0894-0959 (ISSN-L)
- 1525-139X
- OpenAlex
- W2120453226
- Cited by
- 131
- References
- 36
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 7 · 2023: 6 · 2022: 13 · 2021: 14 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 12 · 2012: 2
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Dialysis (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- uremic toxins, guanidino compounds, uremic encephalopathy, neurotoxicity, chronic kidney disease, NMDA receptor, GABAA receptor, guanidinosuccinic acid, methylguanidine, guanidine, creatinine, glutamate receptors, convulsants, cerebrovascular disease, epilepsy, cognitive impairment
- MeSH terms
- Brain, Guanidines, Humans, Toxins, Biological, Uremia
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