Understanding the pathogenesis of haemolytic uraemic syndrome: the role of the podocyte

溶血性尿毒综合征（HUS）是儿童急性肾衰竭的主要原因。1-5%的溶血性尿毒综合征患儿死亡，有些患儿留下慢性肾损害。它通常是由胃肠道感染（大肠杆菌）引起的，在英国每年有1000人感染。它会产生毒素，在10-15%的病例中会导致肾脏和其他器官受损。这是一个公共卫生问题。目前，我们不了解溶血性尿毒综合征是如何引起的，因此管理的重点是支持性护理。我们的合作者最近使用小鼠模型的工作为我们对溶血性尿毒综合征的理解提供了一个潜在的突破。本项目将以此为基础，旨在研究溶血性尿毒综合征对肾脏的影响。它将研究毒素对特定肾细胞的影响。我们将创建一个与人类疾病非常相似的小鼠模型。这部分工程正在进行中。我们还将使用不同的技术来观察人类肾细胞，看看毒素是如何影响它们的，特别是毒素是如何影响这些细胞之间的相互作用的。了解这种疾病是如何影响肾脏的，将找到治疗这种疾病的潜在方法，减轻受影响儿童及其家庭的痛苦。

Haemolytic uraemic syndrome (HUS) is the leading cause of acute kidney failure in children. 1-5%of children with HUS die and some are left with chronic kidney damage. It is commonly caused by agastrointestinal infection (E.coli) that affects >1000 people/year in Britain. It produces toxins, whichin 10-15% of cases causes kidney and other organ damage. It is a public health concern. Currently,we do not understand how HUS is caused and therefore management focuses on supportive care.Recent work by our collaborators using a mouse model has provided a potential breakthrough in ourunderstanding of HUS.This project will build on this and aims to investigate the kidney effects of HUS. It will study theeffects of the toxin on specific kidney cells. We will create a mouse model that closely resembles thedisease in humans. This part of the project is underway. We will also look at human kidney cellsusing different techniques to see how the toxin affects them and, in particular, how the toxin affectsthe interaction between these cells. Understanding how this disease affects the kidney will identifypotential ways of treating this condition and alleviate the suffering of affected children and theirfamilies.