Uremic Toxins and Cardiovascular Disease

2020 ◽  
pp. 69-81
Author(s):  
Toyoaki Murohara
Keyword(s):  
Cardiovascular Disease ◽  
Uremic Toxins

scholarly journals Nontraditional Biomarkers for Cardiovascular Disease in Patients With Chronic Kidney Disease

2020 ◽  
Vol 43 (2) ◽  
pp. 51-60
Author(s):  
Ittikorn Spanuchart ◽  
Arkom Nongnuch ◽  
Youg Liu
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Mineral Metabolism ◽  
Uremic Toxins ◽  
Calcium Balance ◽  
The Novel ◽  
Cvd Risk ◽  
Chd Risk

Cardiovascular disease (CVD) is the leading cause of death among patients who have chronic kidney disease (CKD). Nowadays, CKD per se is considered one of the coronary heart disease (CHD) risk equivalents. Apart from traditional CVD risk factors, there are several possible determinants for CVD in patients with CKD, for example, uremic toxins, increased inflammatory stage, abnormal bone mineral metabolism, and positive calcium balance. In this narrative review, we offer a summary of the extensively studied biomarkers for CVD in patients with CKD, including uremic toxins (p-cresol, indoxyl sulfate, and advanced glycated end products), and a novel indicator of arterial stiffness, cardio-ankle vascular index (CAVI), which is an independent prognostic predictor for CVD. For the uremic toxins, we reviewed their metabolisms, particularly, how the reduced renal function in CKD patients affect their clearance and their clearance with dialysis. Also, we pay attention to the recent evidence on how those uremic toxins contribute to CVD and their clinical associations. We do not include the possible treatment targeting at those uremic toxins. As for the novel indicator of arterial stiffness, we reviewed the clinical application of CAVI in comparison to the standard indicator for arterial stiffness, pulse wave velocity.  

scholarly journals Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-15 ◽  
Author(s):  
Ewa Wojtaszek ◽  
Urszula Oldakowska-Jedynak ◽  
Marlena Kwiatkowska ◽  
Tomasz Glogowski ◽  
Jolanta Malyszko
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Uremic Toxins ◽  
Transplant Recipients ◽  
Risk Of Death ◽  
The Impact

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function.

scholarly journals Immune Dysfunction in Uremia 2020

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 439
Author(s):  
Gerald Cohen
Keyword(s):  
Cardiovascular Disease ◽  
Immune System ◽  
Immune Cells ◽  
Protein Profile ◽  
Density Lipoprotein ◽  
Uremic Toxins ◽  
Water Soluble ◽  
Retinol Binding Protein ◽  
Intestinal Microbiome ◽  
The Impact

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties.

The guanylate cyclase C agonist linaclotide ameliorates the gut–cardio–renal axis in an adenine-induced mouse model of chronic kidney disease

2019 ◽  
Author(s):  
Fumika Nanto-Hara ◽  
Yoshitomi Kanemitsu ◽  
Shinji Fukuda ◽  
Koichi Kikuchi ◽  
Kei Asaji ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Cardiac Fibrosis ◽  
Cardiorenal Syndrome ◽  
Uremic Toxins ◽  
Guanylate Cyclase C

Abstract Background Cardiorenal syndrome is a major cause of mortality in patients with chronic kidney disease (CKD). However, the involvement of detrimental humoral mediators in the pathogenesis of cardiorenal syndrome is still controversial. Trimethylamine-N-oxide (TMAO), a hepatic metabolic product of trimethylamine generated from dietary phosphatidylcholine or carnitine derived by the gut microbiota, has been linked directly with progression of cardiovascular disease and renal dysfunction. Thus, targeting TMAO may be a novel strategy for the prevention of cardiovascular disease and chronic kidney disease. Methods Linaclotide, a guanylate cyclase C agonist, was administered to adenine-induced renal failure (RF) mice and changes in renal function and levels of gut-derived uremic toxins, as well as the gut microbiota community, were analyzed using metabolomic and metagenomic methods to reveal its cardiorenal effect. Results Linaclotide decreased the plasma levels of TMAO at a clinically used low dose of 10 μg/kg in the adenine-induced RF mouse model. At a high concentration of 100 μg/kg, linaclotide clearly improved renal function and reduced the levels of various uremic toxins. A reduction in TMAO levels following linaclotide treatment was also observed in a choline-fed pro-atherosclerotic model. Linaclotide ameliorated renal inflammation and fibrosis and cardiac fibrosis, as well as decreased the expression of collagen I, transforming growth factor-β, galectin-3 (Gal-3) and ST2 genes. Plasma levels of Gal-3 and ST2 were also reduced. Because exposure of cardiomyocytes to TMAO increased fibronectin expression, these data suggest that linaclotide reduced the levels of TMAO and various uremic toxins and may result in not only renal, but also cardiac, fibrosis. F4/80-positive macrophages were abundant in small intestinal crypts in RF mice, and this increased expression was decreased by linaclotide. Reduced colonic claudin-1 levels were also restored by linaclotide, suggesting that linaclotide ameliorated the ‘leaky gut’ in RF mice. Metagenomic analysis revealed that the microbial order Clostridiales could be responsible for the change in TMAO levels. Conclusion Linaclotide reduced TMAO and uremic toxin levels and could be a powerful tool for the prevention and control of the cardiorenal syndrome by modification of the gut–cardio–renal axis.

scholarly journals Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 142
Author(s):  
Yong Jin Lim ◽  
Nicole A. Sidor ◽  
Nicholas C. Tonial ◽  
Adrian Che ◽  
Bradley L. Urquhart
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Targets ◽  
Free Water ◽  
Uremic Toxins ◽  
Water Soluble ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
Middle Molecules

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.

scholarly journals Dysbiosis-Related Advanced Glycation Endproducts and Trimethylamine N-Oxide in Chronic Kidney Disease

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 361
Author(s):  
Kensei Taguchi ◽  
Kei Fukami ◽  
Bertha C. Elias ◽  
Craig R. Brooks
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Advanced Glycation Endproducts ◽  
Uremic Toxins ◽  
Health Concern ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Gut Dysbiosis ◽  
Microbial Dysbiosis

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.

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