Targeting Uremic Toxins in Chronic Kidney Disease: Novel Therapeutic Approaches

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Uremic Toxins".

Deadline for manuscript submissions: 21 May 2025 | Viewed by 3389

Special Issue Editors


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Guest Editor
CarMeN Lab, INSERM U1060, INRAe U1397, Université Claude Bernard Lyon 1, F-69500 Bron, France
Interests: uremic toxin; uremia; chronic kidney disease; metabolic complications
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Guest Editor
CarMeN Lab, INSERM U1060, INRAe U1397, Université Claude Bernard Lyon 1, F-69500 Bron, France
Interests: uremic toxin; uremia; chronic kidney disease; cardiovascular complications

E-Mail Website
Guest Editor
CarMeN Lab, INSERM U1060, INRAe U1397, Université Claude Bernard Lyon 1, F-69500 Bron, France
Interests: renal nutrition; uremic toxins; chronic kidney disease; metabolic complications

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a progressive condition marked by the gradual loss of kidney function, leading to the accumulation of harmful substances often referred to as uremic toxins. As kidney function deteriorates, the body accumulates these harmful substances that would normally be excreted in the urine. These uremic toxins contribute to a wide range of complications, including cardiovascular diseases, low-grade inflammation, and further kidney damage, thereby accelerating CKD progression. Traditional treatments primarily focus on controlling blood pressure, blood sugar, and other risk factors to slow kidney function decline. However, these approaches often fail to adequately address the buildup of uremic toxins, leaving patients vulnerable to their deleterious effects. Recent advancements in our understanding of CKD pathophysiology have spurred the development of novel therapeutic approaches specifically aimed at targeting uremic toxins. These include strategies such as the use of adsorbents that bind and neutralize toxins in the gastrointestinal tract, probiotics and prebiotics that alter gut microbiota to reduce toxin production, innovative pharmacological agents that enhance toxin removal or inhibit their harmful effects, and new technologies of dialysis. By focusing directly on reducing the burden of uremic toxins, these emerging therapies offer the potential to improve outcomes for CKD patients, providing a new frontier in the management of this chronic and debilitating disease.

This Special Issue of Toxins will focus on novel and emerging technologies, drugs, or nutritional approaches that have been studied and developed to decrease production, enhance removal, or prevent the toxicity of uremic toxins. Original research articles, reviews, and methodological papers are welcome.

Prof. Dr. Christophe O. Soulage
Prof. Dr. Fitsum Guebre-Egziabher
Dr. Laetitia Koppe
Guest Editors

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Keywords

  • uremic toxins
  • dialysis
  • hemodialysis
  • gut microbiota
  • prebiotics
  • probiotics
  • adsorbents
  • protein-bound uremic toxins

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Published Papers (2 papers)

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Research

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11 pages, 1452 KiB  
Article
Trimethylamine N-Oxide (TMAO) Plasma Levels in Patients with Different Stages of Chronic Kidney Disease
by Marcia Ribeiro, Julie Ann Kemp, Ludmila Cardozo, Drielly Vargas, Marcelo Ribeiro-Alves, Peter Stenvinkel and Denise Mafra
Toxins 2025, 17(1), 15; https://doi.org/10.3390/toxins17010015 - 31 Dec 2024
Cited by 1 | Viewed by 1152
Abstract
Background: In patients with chronic kidney disease (CKD), trimethylamine n-oxide (TMAO) accumulation exacerbates inflammation and contributes to oxidative stress. These complications are putatively linked to the development of cardiovascular diseases. Despite the known associations, the variation in TMAO plasma levels across different CKD [...] Read more.
Background: In patients with chronic kidney disease (CKD), trimethylamine n-oxide (TMAO) accumulation exacerbates inflammation and contributes to oxidative stress. These complications are putatively linked to the development of cardiovascular diseases. Despite the known associations, the variation in TMAO plasma levels across different CKD stages and dialysis modalities remains underexplored. This study aimed to quantify TMAO plasma levels in different CKD stages and dialysis treatments. Methods: This cross-sectional study assessed TMAO plasma levels in non-dialysis CKD patients (ND), patients undergoing hemodialysis (HD), and peritoneal dialysis (PD). TMAO plasma levels were assessed by liquid chromatography coupled to triple mass spectrometry quadrupole. Results: In total, 15 ND patients [stages 3–5, glomerular filtration rate 41.4 mL/min/1.73 m2, 64 (IQR = 12.5) years, BMI 25.2 kg/m2, eight women]; 14 PD patients [57.5 (IQR = 8.5) years, BMI of 27.8 kg/m2, nine women]; and 34 HD patients [43.5 (IQR = 45.5) years, BMI of 24.4 kg/m2, nineteen women] were analyzed. ND patients had lower TMAO levels when compared to the HD (p < 0.0001) and PD patients (p = 0.001). There was no difference in TMAO levels between patients undergoing dialysis (p < 0.59). There was a negative correlation between TMAO and HDL plasma levels [rho = −0.380 (p < 0.004)], calcium [rho = −0.321 (p < 0.016)], and albumin [rho = −0.416 (p < 0.001)]. In addition, a positive correlation between TMAO and urea levels was observed [rho = 0.717 (p < 0.001)]. Conclusions: CKD stages impact TMAO levels since patients on non-dialysis treatment had lower levels than patients on HD and PD. Full article
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23 pages, 1396 KiB  
Review
Gut Dysbiosis and Its Role in the Anemia of Chronic Kidney Disease
by Elisabet Coll, Secundino Cigarran, Jose Portolés and Aleix Cases
Toxins 2024, 16(11), 495; https://doi.org/10.3390/toxins16110495 - 17 Nov 2024
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Abstract
The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in [...] Read more.
The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in the intestinal microbiota composition in CKD, may lead to the development or worsening of anemia in renal patients. Understanding and addressing these mechanisms related to gut dysbiosis in CKD patients can help to delay the development of anemia and improve its control in this population. One approach is to avoid or reduce the use of drugs linked to gut dysbiosis in CKD, such as phosphate binders, oral iron supplementation, antibiotics, and others, unless they are indispensable. Another approach involves introducing dietary changes that promote a healthier microbiota and/or using prebiotics, probiotics, or symbiotics to improve gut dysbiosis in this setting. These measures can increase the presence of SCFA-producing saccharolytic bacteria and reduce proteolytic bacteria, thereby lowering the production of gut-derived uremic toxins and inflammation. By ameliorating CKD-related gut dysbiosis, these strategies can also improve the control of renal anemia and enhance the response to erythropoiesis-stimulating agents (ESAs) in ESA-resistant patients. In this review, we have explored the relationship between gut dysbiosis in CKD and renal anemia and propose feasible solutions, both those already known and potential future treatments. Full article
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