Nephrotic syndrome disease activity is proportional to its associated hypercoagulopathy.
Nephrotic syndrome disease activity is proportional to its associated hypercoagulopathy.
复制标题
DOI：
10.1016/j.thromres.2021.02.007
复制
发表时间：
2021-05
影响因子：
7.5
通讯作者：
NEPTUNE Investigators
中科院分区：
文献类型：
--
作者：
Waller AP;Troost JP;Parikh SV;Wolfgang KJ;Rovin BH;Nieman MT;Smoyer WE;Kretzler M;Kerlin BA;NEPTUNE Investigators
肾病综合征（NS）与获得性高凝血症相关，后者导致其对危及生命的血栓形成的强烈偏好。我们先前在动物模型中证明了高凝障碍与NS疾病的严重程度成正比。因此，高凝血症和疾病严重程度可以告知血栓形成风险，并更好地指导治疗决策。因此，本研究的目的是建立疾病严重程度和高凝血症之间的关系，在人类NS。对来自前瞻性纵向NS队列研究的生物储存血浆样本进行凝血酶生成试验（TGA）。TGA还确定了一个单独的队列事件NS患者。采用多元回归分析建立NS与高凝状态的关系模型。内源性凝血酶电位（ETP）是与NS严重程度最密切相关的TGA参数，与NS疾病活动度的常规指标（包括蛋白尿、高胆固醇血症和低白蛋白血症）成比例。总体疾病活动模型与ETP有很好的相关性（R2=0.38）。在第二个队列中证实了与疾病活动的关系。这些模型进一步揭示了ETP以依赖于缓解状态的方式与疾病活动相关。与我们先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定义的高凝血病相关。NS部分或完全缓解后，高凝状态显著改善。预计这些数据将为旨在对NS患者的血栓形成风险进行分层的研究提供信息。
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 (R2=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.
登录
查看更多内容
影响因子：
7.5
作者：
Dargaud, Y.;Luddington, R.;Negrier, C.
通讯作者：
Negrier, C.
影响因子：
10.4
作者：
Attard, C.;van der Straaten, T.;Ignjatovic, V.
通讯作者：
Ignjatovic, V.
影响因子：
12.8
作者：
Emani, Sirisha;Zurakowski, David;Emani, Sitaram M.
通讯作者：
Emani, Sitaram M.
影响因子：
4
作者：
Heit, John A.;Spencer, Frederick A.;White, Richard H.
通讯作者：
White, Richard H.
DOI：
10.1016/s0735-1097(97)00129-0
发表时间：
1997-07-01
影响因子：
24
作者：
Aoki, I;Aoki, N;Ishikawa, K
通讯作者：
Ishikawa, K