Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

Abstract

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD14/CD16, CD14/CD16) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14/CD16 and CD14/CD16), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

“…Elimination of EVs is currently used as a therapeutic strategy . Endothelial MVs can serve as useful biomarkers of CKD (Carmona et al, 2017a) because endothelial damage is associated with CKD, and the release of EVs is enhanced during endothelial injury. Uremic toxins (such as IS) also induce a release of endothelial MVs (Carmona et al, 2017b).…”

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

“…Like other pathologies, EVs represent phenotypic markers of cellular stress and activation in CKD. More importantly, their number and composition may also play a role in the pathophysiology of cardiovascular complications, and thus in mortality risk (Carmona et al, 2017a).…”

“…Generally, research on EVs is a challenge for the scientific community, mainly due to their size, heterogeneity, artificial generation during the preanalytical stages, and lack of standardized methods of working with them (Doyle and Wang, 2019). Let alone studying them in CKD patients characterized by extreme variabilities in primary lesions, comorbidities, and treatments, which individually and in synergy affect both their release and composition (Carmona et al, 2017a).…”

Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction

“…Prior to the sample acquisition, the samples were subjected to a separate and combined labeling reaction using all reactive (monoclonal antibodies, Annexin V, and the appropriate negative controls) to compensate for the fluorescence using compensation tools on the flow cytometer. In a previous study, we established a MV gate on the FC 500 cytometer using a blend of size-calibrated beads with diameters of 0.3, 0.5, and 1.0 μm (Carmona et al, 2017 ). The upper and outer limits of the MV gate were established just above the size distribution of the 1-μm beads in the forward (FSC-A) and side scatter (SSC-A) settings (log scale).…”