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Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets.
Toxins (Basel). 2021 02 13; 13(2)T

Abstract

Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada. Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada. Lawson Health Research Institute, London, ON N6A 3K7, Canada.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33668632

Citation

Lim, Yong Jin, et al. "Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets." Toxins, vol. 13, no. 2, 2021.
Lim YJ, Sidor NA, Tonial NC, et al. Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins (Basel). 2021;13(2).
Lim, Y. J., Sidor, N. A., Tonial, N. C., Che, A., & Urquhart, B. L. (2021). Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins, 13(2). https://doi.org/10.3390/toxins13020142
Lim YJ, et al. Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins (Basel). 2021 02 13;13(2) PubMed PMID: 33668632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. AU - Lim,Yong Jin, AU - Sidor,Nicole A, AU - Tonial,Nicholas C, AU - Che,Adrian, AU - Urquhart,Bradley L, Y1 - 2021/02/13/ PY - 2020/12/22/received PY - 2021/02/08/revised PY - 2021/02/10/accepted PY - 2021/3/6/entrez PY - 2021/3/7/pubmed PY - 2021/7/1/medline KW - asymmetric dimethylarginine KW - cardiovascular disease KW - chronic kidney disease KW - hippuric acid KW - indoxyl sulfate KW - interleukin 6 KW - p-cresyl sulfate KW - trimethylamine N-oxide KW - tumor necrosis factor al-pha KW - uremic toxins JF - Toxins JO - Toxins (Basel) VL - 13 IS - 2 N2 - Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/33668632/Uremic_Toxins_in_the_Progression_of_Chronic_Kidney_Disease_and_Cardiovascular_Disease:_Mechanisms_and_Therapeutic_Targets_ L2 - https://www.mdpi.com/resolver?pii=toxins13020142 DB - PRIME DP - Unbound Medicine ER -