Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Nephrol Dial Transplant. 2013 Aug;28(8):2116-22. doi: 10.1093/ndt/gft103. Epub 2013 May 31.
Chronic kidney disease (CKD) is a common co-morbidity of patients with atherosclerotic vascular disease, and may influence the response to antiplatelet therapy. We, therefore, sought to investigate its effect on platelet activation and on-treatment residual platelet reactivity.
We assessed platelet activation and the response to clopidogrel and aspirin in 316 patients after percutaneous intervention with stent implantation. CKD was defined as a glomerular filtration rate <60 mL/min/1.73 m(2) according to the Modification of Diet in Renal Disease formula. Surface expression of activated glycoprotein IIb/IIIa without the addition of agonists was determined to assess baseline platelet activation. GPIIb/IIIa in response to adenosine diphosphate (ADP) and arachidonic acid (AA), as well as the VerifyNow assays and light transmission aggregometry (LTA) were used to measure residual platelet reactivity.
Baseline platelet activation was significantly increased in CKD patients compared with patients without renal insufficiency [3.1 versus 2.7 mean fluorescence intensity (MFI), P = 0.001]. Moreover, patients with CKD exhibited a more pronounced expression of GPIIb/IIIa in response to ADP (13 versus 9.6 MFI) and AA (6 versus 5.1 MFI; both P≤ 0.02) than patients without CKD. In the VerifyNow assays, CKD patients showed significantly higher platelet reactivity than patients without CKD (P2Y12 assay: 239 versus 182 P2Y12 Reaction Units; aspirin assay: 415 versus 399 Aspirin Reaction Units; both P≤ 0.03). Further, patients with CKD had significantly higher platelet reactivity by LTA in response to ADP (49.9 versus 43.2%, P = 0.01). Finally, high on-treatment residual ADP-inducible platelet reactivity by the VerifyNow P2Y12 assay and by LTA occurred significantly more frequent in patients with CKD (VerifyNow: 52.2 versus 26.2%, P < 0.001; LTA: 23.3 versus 12.1%, P = 0.01).
Patients with CKD exhibit increased platelet activation, and an attenuated response to dual antiplatelet therapy compared with patients without renal insufficiency.
慢性肾脏病（CKD）是动脉粥样硬化性血管疾病患者常见的合并症，可能影响抗血小板治疗的反应。因此，我们旨在研究其对血小板激活和治疗后残余血小板反应性的影响。
我们评估了 316 例经皮冠状动脉介入治疗后植入支架的患者的血小板激活和氯吡格雷及阿司匹林的反应。根据改良肾脏病膳食研究公式，将 CKD 定义为肾小球滤过率<60mL/min/1.73m²。测定无激动剂时激活糖蛋白 IIb/IIIa 的表面表达，以评估基线血小板激活。用二磷酸腺苷（ADP）和花生四烯酸（AA）测定 GPIIb/IIIa，以及 VerifyNow 测定法和光传输聚集测定法（LTA），以测量残余血小板反应性。
与肾功能正常的患者相比，CKD 患者的基线血小板激活显著增加[3.1 与 2.7 平均荧光强度（MFI），P=0.001]。此外，CKD 患者对 ADP（13 与 9.6 MFI）和 AA（6 与 5.1 MFI；均 P≤0.02）的 GPIIb/IIIa 表达更为明显。在 VerifyNow 测定法中，CKD 患者的血小板反应性明显高于肾功能正常的患者（P2Y12 测定法：239 与 182 P2Y12 反应单位；阿司匹林测定法：415 与 399 阿司匹林反应单位；均 P≤0.03）。此外，CKD 患者对 ADP 的 LTA 反应性血小板反应性显著升高（49.9 与 43.2%，P=0.01）。最后，CKD 患者通过 VerifyNow P2Y12 测定法和 LTA 测定法的高治疗后残余 ADP 诱导性血小板反应性显著更为频繁（VerifyNow：52.2 与 26.2%，P<0.001；LTA：23.3 与 12.1%，P=0.01）。
与肾功能正常的患者相比，CKD 患者的血小板激活增加，对双联抗血小板治疗的反应减弱。
