Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro.

Vascular calcification (VC), an unpredictable pathophysiological process and critical event in patients with cardiovascular diseases (CVDs), is the leading cause of morbi-mortality and disability in chronic kidney disease (CKD) patients worldwide. Currently, no diagnostic method is available for identifying patients at risk of VC development; the pathology is detected when the process is irreversible. Extracellular vesicles (EVs) from endothelial cells might promote VC. Therefore, their evaluation and characterization could be useful for designing new diagnostic tools. The aim of the present study is to investigate whether microvesicles (MVs) from endothelial cells damaged by uremic toxin and indoxyl sulfate (IS) could induce calcification in human vascular smooth muscle cells (VMSCs). Besides, we have also analyzed the molecular mechanisms by which these endothelial MVs can promote VC development. Endothelial damage has been evaluated according to the percentage of senescence in endothelial cells, differential microRNAs in endothelial cells, and the amount of MVs released per cell. To identify the role of MVs in VC, VSMCs were treated with MVs from IS-treated endothelial cells. Calcium, inflammatory gene expression, and procalcification mediator levels in VSMCs were determined. IS-treated endothelial cells underwent senescence and exhibited modulated microRNA expression and an increase in the release of MVs. VSMCs exposed to these MVs modulated the expression of pro-inflammatory genes and some mediators involved in calcification progression. MVs produced by IS-treated endothelial cells promoted calcification in VSMCs.

Statins and antiplatelet agents are associated with changes in the circulatory markers of endothelial dysfunction in chronic kidney disease. / El uso de estatinas y antiagregantes se asocia con cambios en los marcadores de disfunción endotelial en la enfermedad renal crónica.

BACKGROUNDS AND PURPOSES: Patients with chronic kidney disease (CKD) have higher risk of developing cardiovascular disease. In CKD patients the mechanisms involved in, endothelial damage and the role of different drugs used on these patients are not completely understood. The aim of this work is to analyze the effect of statins and platelet antiaggregant (PA) on endothelial microvesicles (EMVs) and other markers of endothelial dysfunction. EXPERIMENTAL APPROACH: Cross-sectional study of 41 patients with CKD 3b-4 and 8 healthy volunteers. Circulating levels of EMVs, vascular endothelial growth factor (VEGF), and advance oxidized protein products (AOPPS) were quantified and the correlation with different comorbidity variables and therapeutic strategies were evaluated. RESULTS: EMVs are increased in CKD patients as compared with controls (171.1 vs. 68.3/µl, P<.001). It was observed a negative correlation between age and EMVs. Statins and PA were associated with a reduction in EMVs and VEGF levels, independently of the serum total cholesterol levels (TC). The levels of AOPPS and VEGF were not different in CKD vs. controls. CONCLUSION: CKD is associated with a change in EMVs, VEGF and AOPP levels. The treatment with statins and PA normalizes these values to almost the observed in controls and this effect is independently of the prevailing TC level. These findings explain the existence of the pleiotropic effects of statins and PA which deserve further studies.

Residual Renal Function in Hemodialysis and Inflammation.

Residual renal function (RRF) has an important effect on uremic toxin clearance, on volume control, on quality of life, and on mortality. In patients with chronic kidney disease (CKD), microinflammation with an increased percentage of CD14+ /CD16++ inflammatory monocytes has been reported, even with no clinical evidence of inflammation. No correlation has been established between these and RRF in hemodialysis (HD) patients. Our objective was to assess the relationship between RRF and the inflammatory parameters in HD patients. Cross-sectional observational study was carried out on 69 adult patients on chronic HD for at least 6 months, from which demographic, analytic and HD-technique data were collected and the following were measured: (i) RRF with average urea and creatinine clearance ((CCr + CU)/2) in 24-h urine (if >1 mL/min and diuresis >100 mL/day, RRF was considered); (ii) Inflammation through biochemical parameters (C-reactive protein, ß2 microglobulin, albumin) and monocyte subpopulations in peripheral blood. The average age was 70.9 [40-88] years old; 38 (55.1%) were male; and 25 (36.2%) were diabetic. 43.5% (30/69) presented RRF, with an average of ((CCr + CU)/2): 1.8 (2.6) mL/min and diuresis: 454.5 (569) mL /24 h. Patients with RRF presented lower concentrations of C-reactive protein (6.2 vs 21.4 mg/L) (P = 0.038) and a lower percentage of non-classical CD14+ /CD16++ monocytes (14.6 vs. 28.3%, P = 0.02). In our study, patients with RRF present lower concentrations of inflammatory parameters, which is another reason why its preservation is an essential objective in HD.