Waller Amanda P, Troost Jonathan P, Parikh Samir V, Wolfgang Katelyn J, Rovin Brad H, Nieman Marvin T, Smoyer William E, Kretzler Matthias, Kerlin Bryce A
Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children's, Columbus, OH, USA.
Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI, USA.
Thromb Res. 2021 May;201:50-59. doi: 10.1016/j.thromres.2021.02.007. Epub 2021 Feb 16.
Nephrotic syndrome (NS) is associated with an acquired hypercoagulopathy that drives its strong predilection for life-threatening thrombosis. We previously demonstrated that hypercoagulopathy is proportional to NS disease severity in animal models. Therefore, hypercoagulopathy and disease severity may inform thrombosis risk and better guide therapeutic decision making. The objective of this study was thus to establish the relationship between disease severity and hypercoagulopathy in human NS.
Thrombin generation assays (TGA) were performed on biorepository plasma samples from a prospective longitudinal NS cohort study. TGA was also determined on a separate cohort of incident NS patients. Multivariable regression was used to build NS-hypercoagulopathy relationship models.
Endogenous thrombin potential (ETP) was the TGA parameter most strongly correlated with NS severity and was proportional to conventional measures of NS disease activity including proteinuria, hypercholesterolemia, and hypoalbuminemia. The overall disease activity model was well correlated with ETP (R = 0.38). The relationship with disease activity was confirmed in the second cohort. These models further revealed that ETP is related to disease activity in a manner dependent on remission status.
Consistent with our previously reported animal model observations, we found that the combination of proteinuria, hypercholesterolemia, and hypoalbuminemia correlated with ETP-defined hypercoagulopathy. Hypercoagulopathy improved significantly with partial or complete NS remission. These data are expected to inform studies designed to stratify thrombotic risk for patients with NS.
肾病综合征（NS）与获得性高凝状态相关，这种高凝状态使其极易发生危及生命的血栓形成。我们之前在动物模型中证明，高凝状态与NS疾病严重程度成正比。因此，高凝状态和疾病严重程度可能有助于评估血栓形成风险，并更好地指导治疗决策。本研究的目的是确定人类NS中疾病严重程度与高凝状态之间的关系。
对一项前瞻性纵向NS队列研究的生物样本库血浆样本进行凝血酶生成试验（TGA）。还对另一组新诊断的NS患者进行了TGA测定。采用多变量回归建立NS-高凝状态关系模型。
内源性凝血酶潜力（ETP）是与NS严重程度相关性最强的TGA参数，并且与NS疾病活动的传统指标（包括蛋白尿、高胆固醇血症和低白蛋白血症）成正比。整体疾病活动模型与ETP具有良好的相关性（R = 0.38）。在第二个队列中证实了与疾病活动的关系。这些模型进一步表明，ETP与疾病活动的关系取决于缓解状态。
与我们之前报道的动物模型观察结果一致，我们发现蛋白尿、高胆固醇血症和低白蛋白血症的组合与ETP定义的高凝状态相关。随着NS部分或完全缓解，高凝状态显著改善。这些数据有望为旨在对NS患者的血栓形成风险进行分层的研究提供参考。
