Holzer Michael, Schilcher Gernot, Curcic Sanja, Trieb Markus, Ljubojevic Senka, Stojakovic Tatjana, Scharnagl Hubert, Kopecky Chantal M, Rosenkranz Alexander R, Heinemann Akos, Marsche Gunther
Institute of Experimental and Clinical Pharmacology.
Clinical Division of Nephrology, Department of Internal Medicine.
J Am Soc Nephrol. 2015 Sep;26(9):2267-76. doi: 10.1681/ASN.2014030309. Epub 2015 Mar 5.
Lipid abnormalities may have an effect on clinical outcomes of patients on dialysis. Recent studies have indicated that HDL dysfunction is a hallmark of ESRD. In this study, we compared HDL composition and metrics of HDL functionality in patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) with those in healthy controls. We detected a marked suppression of several metrics of HDL functionality in patients on HD or PD. Compositional analysis revealed that HDL from both dialysis groups shifted toward a more proinflammatory phenotype with profound alterations in the lipid moiety and protein composition. With regard to function, cholesterol efflux and anti-inflammatory and antiapoptotic functions seemed to be more severely suppressed in patients on HD, whereas HDL-associated paraoxonase activity was lowest in patients on PD. Quantification of enzyme activities involved in HDL metabolism suggested that HDL particle maturation and remodeling are altered in patients on HD or PD. In summary, our study provides mechanistic insights into the formation of dysfunctional HDL in patients with ESRD who are on HD or PD.
脂质异常可能会对透析患者的临床结局产生影响。近期研究表明,高密度脂蛋白(HDL)功能障碍是终末期肾病(ESRD)的一个标志。在本研究中,我们比较了接受血液透析(HD)或腹膜透析(PD)的患者与健康对照者的HDL组成及HDL功能指标。我们检测到HD或PD患者的多项HDL功能指标受到显著抑制。成分分析显示,两个透析组的HDL均向更具促炎表型转变,脂质部分和蛋白质组成发生了深刻变化。在功能方面,HD患者的胆固醇流出以及抗炎和抗凋亡功能似乎受到更严重的抑制,而PD患者的HDL相关对氧磷酶活性最低。参与HDL代谢的酶活性定量分析表明,HD或PD患者的HDL颗粒成熟和重塑发生了改变。总之,我们的研究为接受HD或PD治疗的ESRD患者中功能失调的HDL形成提供了机制方面的见解。