The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients

Abstract

Extracellular vesicles (EVs) are membrane-enclosed nanoparticles released by most cells in body fluids and extracellular matrix. They function as signal transducers in intercellular communication, contributing to the maintenance of cell and tissue integrity. EVs biogenesis is deregulated in various pathologies, in structural and functional connection to the pathophysiology of donor cells. Consequently, EVs are considered diagnostic and monitoring factors in many diseases. Despite consensus as to their activity in promoting coagulation and inflammation, there is evidence suggesting protective roles for EVs in stress states. Chronic kidney disease (CKD) patients are at high risk of developing cardiovascular defects. The pathophysiology, comorbidities, and treatment of CKD may individually and in synergy affect extracellular vesiculation in the kidney, endothelium, and blood cells. Oxidative and mechanical stresses, chronic inflammation, and deregulation of calcium and phosphate homeostasis are established stressors of EV release. EVs may affect the clinical severity of CKD by transferring biological response modifiers between renal, vascular, blood, and inflammatory cells. In this Review, we focus on EVs circulating in the plasma of CKD patients. We highlight some recent advances in the understanding of their biogenesis, the effects of dialysis, and pharmacological treatments on them and their potential impact on thrombosis and vascular defects. The strong interest of the scientific community to this exciting field of research may reveal hidden pieces in the pathophysiology of CKD and thus, innovative ways to treat it. Overcoming gaps in EV biology and technical difficulties related to their size and heterogeneity will define the success of the project.

Exploring New Kingdoms: The Role of Extracellular Vesicles in Oxi-Inflamm-Aging Related to Cardiorenal Syndrome

“…We have represented in Table 1 that EVs participate in the etiopathogenesis of multiple CVDs, particularly in the onset of kidney diseases [ 185 ]. Therefore, there is great interest in evaluating the changes in EV levels in response to drug treatment [ 26 , 186 ]. On the one hand, there is the possibility of acting at the production and release of EVs.…”

“…On the one hand, there is the possibility of acting at the production and release of EVs. On the other hand, current difficulties which influence both processes should always be considered because the cellular mechanisms involved are not completely clear [ 26 , 186 ].…”

“…During CKD progression due to the accumulation of uremic toxins, EVs generated from different cell types induce endothelial dysfunction because they are responsible for increasing oxidative stress, reducing the bioavailability of nitric oxide, and producing chronic cardiovascular inflammation [ 26 , 190 ]. Knowledge regarding their formation and release represents an attractive therapeutic target to limit EV levels, but the release mechanisms are not fully elucidated.…”

“…Knowledge regarding their formation and release represents an attractive therapeutic target to limit EV levels, but the release mechanisms are not fully elucidated. As far as we know, direct or indirect inhibition of EV generation and/or liberation is a more effective proposal in CKD and other inflammatory diseases [ 26 , 191 ].…”

“…However, elevated plasma levels of EVs are involved in the etiopathogenesis of many chronic inflammatory diseases. They have been detected in patients with cardiovascular risk factors (diabetes, hypertension, peripheral vascular disease, heart failure), aged people, and individuals who have suffered from CKD and cancer [ 25 , 26 , 27 ]. Thus, EVs are emerging as promising candidates in clinical diagnosis and a possible alternative in monitoring the therapeutic follow-up, acting as biomarkers due to their involvement in developing senescence in chronic inflammatory pathologies, such as CVD-associated-CKD [ 26 , 28 ].…”