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探索补体系统、内皮损伤和微小RNA在肾移植后血栓性微血管病中的作用。

Exploring the role of the complement system, endothelial injury, and microRNAs in thrombotic microangiopathy after kidney transplantation.

作者信息

Aleš Rigler Andreja, Večerić-Haler Željka, Arnol Miha, Perše Martina, Boštjančič Emanuela, Pleško Jerica, Simčič Saša, Kojc Nika

机构信息

Department of Nephrology, University Medical Centre Ljubljana, Slovenia.

Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Slovenia.

出版信息

J Int Med Res. 2020 Dec;48(12):300060520980530. doi: 10.1177/0300060520980530.

Abstract

OBJECTIVE

We investigated whether the recipient's complement system function, kidney graft endothelial ultrastructural injury, and microRNA (miRNA) expression before transplantation may be associated with the risk of posttransplant thrombotic microangiopathy (TMA).

METHODS

Complement system function assessment, histological and ultrastructural examination of preimplantation and kidney graft biopsies, and microRNA assessment were performed on kidney transplant recipients (KTRs) with TMA.

RESULTS

On the basis of the clinical course, histological findings, and miRNA patterns, the following two TMA phenotypes were observed: a self-limiting disease that was localized to the kidney graft and a systemic disease that progressed to graft failure without timely treatment. Decreased alternative complement pathway activity and ultrastructural endothelial injury before transplantation were confirmed in all five KTRs and four of five KTRs, respectively, but they did not correlate with TMA severity.

CONCLUSIONS

Alternative complement pathway abnormalities in KTRs and endothelial ultrastructural injury on preimplantation biopsy might be associated with posttransplant TMA, although they did not predict posttransplant TMA severity (localized systemic). The specific miRNA expression patterns in preimplantation kidney graft biopsies demonstrated a borderline statistically significant difference and might provide more accurate information on posttransplant TMA severity.

摘要

目的

我们研究了移植前受者的补体系统功能、肾移植内皮超微结构损伤以及微小RNA(miRNA)表达是否可能与移植后血栓性微血管病(TMA)的风险相关。

方法

对患有TMA的肾移植受者(KTR)进行补体系统功能评估、植入前和肾移植活检的组织学及超微结构检查以及miRNA评估。

结果

根据临床病程、组织学发现和miRNA模式,观察到以下两种TMA表型:局限于肾移植的自限性疾病和未经及时治疗进展为移植失败的全身性疾病。分别在所有5名KTR和5名KTR中的4名中证实了移植前替代补体途径活性降低和超微结构内皮损伤,但它们与TMA严重程度无关。

结论

KTR中的替代补体途径异常和植入前活检时的内皮超微结构损伤可能与移植后TMA相关,尽管它们不能预测移植后TMA的严重程度(局限性 全身性)。植入前肾移植活检中特定的miRNA表达模式显示出边缘统计学显著差异,可能提供有关移植后TMA严重程度的更准确信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f60/7783899/dd2ae5c55072/10.1177_0300060520980530-fig1.jpg

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