Citrate anion improves chronic dialysis efficacy, reduces systemic inflammation and prevents Chemerin-mediated microvascular injury

Abstract

Systemic inflammation and uremic toxins (UT) determine the increased cardiovascular mortality observed in chronic hemodialysis (HD) patients. Among UT, the adipokine Chemerin induces vascular dysfunction by targeting both endothelial and vascular smooth muscular cells (EC and VSMC). As Citrate anion modulates oxidative metabolism, systemic inflammation and vascular function, we evaluated whether citrate-buffered dialysis improves HD efficiency, inflammatory parameters and chemerin-mediated microvascular injury. 45 patients were treated in sequence with acetate, citrate and, again, acetate-buffered dialysis solution (3 months per interval). At study admission and after each treatment switch, we evaluated dialysis efficacy and circulating levels of chemerin and different inflammatory biomarkers. In vitro , we stimulated EC and VSMC with patients’ plasma and we investigated the role of chemerin as UT. Citrate dialysis increased HD efficacy and reduced plasma levels of CRP, fibrinogen, IL6 and chemerin. In vitro , patients’ plasma induced EC and VSMC dysfunction. These effects were reduced by citrate-buffered solutions and paralleled by the decrease of chemerin levels. Consistently, chemerin receptor knockdown reduced EC and VSMC dysfunction. In conclusion, Switching from acetate to citrate improved dialysis efficacy and inflammatory parameters; in vitro , chemerin-induced EC and VSMC injury were decreased by using citrate as dialysis buffer.

Increasing the Magnesium Concentration in Various Dialysate Solutions Differentially Modulates Oxidative Stress in a Human Monocyte Cell Line

“…Another study also demonstrated that citrate decreases degranulation of polymorphonuclear leukocytes and platelets and, consequently, reduces oxidative stress and lipid peroxidation during HD [42]. Therefore, our results support that the use of CDF and ACDF containing high Mg concentrations may have possible beneficial effects by reducing oxidative lipid damage during the HD process [11,12,20].…”

“…Moreover, acetate also induces leukocytes activation, promoting increased ROS production and release of inflammatory compounds [13][14][15][16]. Recently, citric acid has been proposed as a valuable alternative to acetate due to its anticoagulant, anti-inflammatory, and antioxidant properties [20]. Indeed, citrate chelates multivalent cations (e.g., calcium, iron, magnesium, etc.)…”

“…Indeed, citrate chelates multivalent cations (e.g., calcium, iron, magnesium, etc.) and reduces complement and leukocytes activation, improving dialysis efficiency [19,20].Magnesium (Mg) is very important for many basic physiological functions in the human body [21]. Epidemiological studies have demonstrated an association between hypomagnesemia (low serum Mg concentration) and CVD-associated mortality in CKD patients [21][22][23][24].…”

“…Indeed, citrate chelates multivalent cations (e.g., calcium, iron, magnesium, etc.) and reduces complement and leukocytes activation, improving dialysis efficiency [19,20].…”

Circulating apelin, chemerin and omentin levels in patients with gestational diabetes mellitus: a systematic review and meta-analysis

“…We found that the year of publication, geographic region, study sample size, BMI, and gestational age were not sources of heterogeneity across the included studies. The binding of chemerin to its receptors can promote the recruitment of macrophages and dendritic cells, and neutrophil activation to produce inflammation [39], and chronic low-grade inflammation has been associated with increased IR [40]. A reduction in chemerin levels may be associated with the development of GDM through decreased insulin sensitivity and attenuated anti-inflammatory capacity [25].…”