Department of Internal Medicine II, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Nephrol Dial Transplant. 2010 Jul;25(7):2265-72. doi: 10.1093/ndt/gfq012. Epub 2010 Feb 10.
Circulating monocytes can be divided into distinct populations according to their expression of surface markers CD14 and CD16. In patients with chronic kidney disease (CKD), the cell fraction expressing high levels of CD14 and CD16 is expanded and the numbers of these cells are predictive for cardiovascular disease. The present pilot study describes the predictive role of a combined biomarker consisting of high numbers of CD14(++)CD16(+) cells together with high expression of angiotensin-converting enzyme (ACE) on these cells for mortality in CKD Stage V(D) (dialysis) patients.
In a prospective observational study, monocyte subpopulations were enumerated and ACE expression was quantified in 74 CKD patients by flow cytometry. Patients were assigned to one of four groups according to monocyte population numbers and ACE expression below and above the respective medians and observed for mortality and cardiovascular events for 46 months.
Patients stratified to the 'high CD14(++)CD16(+), high ACE' group (n = 22) had a dramatically enhanced mortality of 70% at 2 years compared to all other patient groups (mortality 14.8%, HR 4.86 [95% CI 2.17-10.86, P < 0.0001]). Atherosclerosis-associated events predominated among the causes of death.
This study describes a new combined biomarker of monocyte subpopulation numbers together with high expression of ACE that has a striking predictive value for mortality of CKD patients. Further research into the pathophysiologic background of this observation is warranted.
根据表面标志物 CD14 和 CD16 的表达,循环单核细胞可分为不同的群体。在慢性肾脏病(CKD)患者中,表达高水平 CD14 和 CD16 的细胞群扩张,这些细胞的数量可预测心血管疾病。本初步研究描述了由高数量的 CD14(++)CD16(+)细胞与这些细胞上的血管紧张素转换酶(ACE)的高表达组成的联合生物标志物对 CKD 第 V(D)期(透析)患者死亡率的预测作用。
在一项前瞻性观察研究中,通过流式细胞术对 74 例 CKD 患者的单核细胞亚群进行计数,并定量 ACE 表达。根据单核细胞群体数量和 ACE 表达低于和高于各自中位数,将患者分为四组之一,并观察 46 个月的死亡率和心血管事件。
分层到“高 CD14(++)CD16(+), 高 ACE”组(n = 22)的患者在 2 年内死亡率高达 70%,与所有其他患者组相比(死亡率 14.8%,HR 4.86 [95%CI 2.17-10.86,P < 0.0001])。死亡原因以动脉粥样硬化相关事件为主。
本研究描述了单核细胞亚群数量与 ACE 高表达相结合的新联合生物标志物,对 CKD 患者的死亡率具有显著的预测价值。需要进一步研究这一观察结果的病理生理背景。