Uremic Toxins and Cardiovascular Risk in Chronic Kidney Disease: What Have We Learned Recently beyond the Past Findings?

Abstract

Patients with chronic kidney disease (CKD) have an elevated prevalence of atheromatous (ATH) and/or non-atheromatous (non-ATH) cardiovascular disease (CVD) due to an array of CKD-related risk factors, such as uremic toxins (UTs). Indeed, UTs have a major role in the emergence of a spectrum of CVDs, which constitute the leading cause of death in patients with end-stage renal disease. The European Uremic Toxin Work Group has identified over 100 UTs, more than 25 of which are dietary or gut-derived. Even though relationships between UTs and CVDs have been described in the literature, there are few reviews on the involvement of the most toxic compounds and the corresponding physiopathologic mechanisms. Here, we review the scientific literature on the dietary and gut-derived UTs with the greatest toxicity in vitro and in vivo. A better understanding of these toxins’ roles in the elevated prevalence of CVDs among CKD patients might facilitate the development of targeted treatments. Hence, we review (i) ATH and non-ATH CVDs and the respective levels of risk in patients with CKD and (ii) the mechanisms that underlie the influence of dietary and gut-derived UTs on CVDs.

Evolving Concepts on Inflammatory Biomarkers and Malnutrition in Chronic Kidney Disease

“…Even though other sources of inflammation beyond CKD/uremic toxins (more than 25% of which are dietary o gut-derived) [ 24 , 25 , 26 ], such as infections or thrombotic events related to vascular access in HD patients, peritonitis in patients undergoing peritoneal dialysis, infections and immunosuppression in transplant patients, the intrinsic mechanisms associated with the development of a proinflammatory milieu is comparable in all CKD patients [ 2 ]. Further inflammatory factors are summarized in Figure 1 .…”

PCSK9 and Other Metabolic Targets to Counteract Ischemia/Reperfusion Injury in Acute Myocardial Infarction and Visceral Vascular Surgery

“…The incidence of AMI among chronic kidney disease (CKD) patients is more than twice that of individuals without CKD. CKD patients have a high prevalence of atheromatous and/or non-atheromatous CVD; moreover, oxidative stress, systemic inflammation, and the accumulation of uremic toxins secondary to renal dysfunction, which are endogenous compounds with vasoactive properties normally cleared by the kidney, [26] are some of the factors that contribute to heart damage.…”

Changes in Cardiac Function During the Development of Uremic Cardiomyopathy and the Effect of Salvianolic Acid B Administration in a Rat Model

“…Left ventricular hypertrophy is closely related to heart failure ( 2 ). Although scientists termed cardiomyopathy related to renal failure as uremic cardiomyopathy (UC) in 1967, the pathogenesis of UC remains poorly understood due to its multifactorial etiology ( 3 – 5 ).…”

“…Hypertrophy of the LV is a beneficial adaptive response during the early stages of UC, but progressive LV overload leads to maladaptive cardiomyocyte alterations and death ( 4 ). The loss of cardiomyocytes leads to LV dilatation and eventually systolic dysfunction ( 3 ). Thus, different types of LV hypertrophy are observed in UC based on the forces acting on the LV ( 8 ).…”