Baaten Constance C F M J, Sternkopf Marieke, Henning Tobias, Marx Nikolaus, Jankowski Joachim, Noels Heidi
Institute for Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
J Am Soc Nephrol. 2021 Jul;32(7):1583-1598. doi: 10.1681/ASN.2020101440. Epub 2021 May 3.
Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.
To help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.
We included 73 studies in the systematic review to assess CKD's overall effect on platelet function in patients; 11 of them described CKD's effect on platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ; analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.
Overall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.
慢性肾脏病(CKD)患者发生血栓形成和出血并发症的风险很高。血小板功能异常是这些并发症的核心,但关于CKD与血小板功能关系的报道相互矛盾,从血小板反应性降低到正常或增加不等。尿毒症毒素对血小板功能的直接影响已有描述,但结果各异。
为了阐明CKD如何影响血小板功能,我们对CKD患者的血小板活性进行了系统评价和荟萃分析,重点关注非透析引起的影响。我们还广泛检索了关于个别尿毒症毒素对血小板功能影响的文献。
我们在系统评价中纳入了73项研究,以评估CKD对患者血小板功能的总体影响;其中11项描述了CKD对血小板聚集的影响,并纳入了荟萃分析。尽管关于CKD患者血小板异常的研究结果不一致,但出血时间大多延长,血小板黏附主要降低。此外,荟萃分析显示,CKD患者在胶原刺激下最大血小板聚集显著降低。我们还发现,相对较少的尿毒症毒素被检测对血小板的直接影响;分析方法和结果各不相同,显示出对血小板既有刺激作用又有抑制作用。然而,在动物模型中测试的12种尿毒症毒素中有8种大多诱导促血栓形成作用。
总体而言,大多数研究报告CKD患者的血小板功能受损。然而,大量研究发现血小板功能未改变甚至增强。有必要进一步研究CKD患者的血小板反应性,尤其是在不同的CKD阶段。