Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Nephrol Dial Transplant. 2009 Nov;24(11):3454-60. doi: 10.1093/ndt/gfp309. Epub 2009 Jun 23.
Atherosclerosis is an inflammatory disease where oxidized low-density lipoprotein may play an important role through phosphorylcholine (PC)-exposing inflammatory phospholipids. Both atherosclerosis and its clinical consequence cardiovascular disease (CVD) are highly prevalent in patients with end-stage renal disease (ESRD). We here study the association between IgM antibodies against phosphorylcholine-A (anti-PC) and risk of death in patients undergoing haemodialysis (HD).
We performed a prospective observational study examining the relationship between anti-PC concentrations and mortality risk in a well-characterized cohort of 203 prevalent HD patients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 29 (14-58) months.
Median anti-PC levels were lower in HD patients with systemic collagen vascular disease (18.9 versus 45.2 U/mL, P = 0.01) and in patients who died during the follow-up period (29.5 versus 53.9 U/mL; P = 0.0008). The patients with an anti-PC value below the median (42.1 U/mL) had a higher mortality rate with a crude hazard ratio (HR) of 2.13 (95% CI 1.40-3.22). These patients remained at higher risk of death (HR 1.76; 95% CI 1.13-2.74) even after adjustment for traditional risk factors (age, sex, smoking habits, CKD aetiology, CVD and diabetes), protein-energy wasting and inflammation (HR 1.70; 95% CI 1.19-2.68).
Low levels of natural IgM antibodies against PC are independent predictors of death among HD patients. Further studies are needed to define the clinical role of such measurements and to explore potentials for active immunization, with PC as an antigen, or passive immunization, aiming at raising levels of protective anti-PC.
动脉粥样硬化是一种炎症性疾病,其中氧化的低密度脂蛋白可能通过暴露磷酸胆碱(PC)的炎症性磷脂发挥重要作用。动脉粥样硬化及其临床后果心血管疾病(CVD)在终末期肾病(ESRD)患者中非常普遍。我们在此研究了在接受血液透析(HD)的患者中针对磷酸胆碱-A 的 IgM 抗体(抗-PC)与死亡风险之间的关联。
我们进行了一项前瞻性观察性研究,检查了在一个特征明确的 203 例接受 HD 的患者队列中,抗-PC 浓度与死亡率之间的关系[56%为男性,中位年龄 66(四分位间距 51-74)岁,老化时间 29(15-58)个月],平均随访时间为 29(14-58)个月。
患有系统性胶原血管疾病的 HD 患者的抗-PC 水平中位数较低(18.9 与 45.2 U/mL,P=0.01),并且在随访期间死亡的患者中也较低(29.5 与 53.9 U/mL;P=0.0008)。抗-PC 值低于中位数(42.1 U/mL)的患者死亡率更高,粗危险比(HR)为 2.13(95%CI 1.40-3.22)。即使在调整了传统危险因素(年龄、性别、吸烟习惯、CKD 病因、CVD 和糖尿病)、蛋白质能量消耗和炎症(HR 1.76;95%CI 1.13-2.74)后,这些患者仍处于更高的死亡风险中。
针对 PC 的天然 IgM 抗体的低水平是 HD 患者死亡的独立预测因子。需要进一步的研究来确定此类测量的临床作用,并探索以 PC 为抗原的主动免疫或旨在提高保护性抗-PC 水平的被动免疫的潜力。