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Necroinflammation, kidney regeneration, and long term outcomes of acute tubular necrosis

坏死性炎症、肾脏再生和急性肾小管坏死的长期结果

基本信息

批准号：
286730110
负责人：
Professor Dr. Hans-Joachim Anders
金额：
--
依托单位：
Medizinische Klinik und Poliklinik IV
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/286730110?language=en
关键词：
Necroinflammation kidney regeneration long term

项目摘要

Acute tubular necrosis is a clincially important entity of acute kidney injury. There are many reasons why there are still no curative therapeutic options for patients with acute tubular necrosis. This project intends to overcome these limitations by five innovative ideas: 1. Minimizing necroinflammation. Cell necrosis and Inflammation dominate the early and late injury phase of acute tubular necrosis. We will at first determine the therapeutic window of inhibitors of regulated cell necrosis, cytokines and chemokies that have proven effective in preemptive study designs. 2. Promoting intrinsic kidney regeneration. Nephron loss is based on an insufficient tubule regeneration. We will at first determine the therapeutic window of pro-regenerative compounds. 3 Clonal tubular cell proliferation? How many of the necrotic tubular cells are really replaced via proliferation of surviving tubular cells is unknown. We will use lineage tracing of clonal proliferation to at first answer this question. 4. Nephron loss determines long term outcomes. Whether acute tubular necrosis is followed by kidney regeneration or atrophy depends on the number of irreversibly lost Nephrons. We will quantify nephron loss and use it as a primary end point for all therapeutic interventions. 5. Sequential combination therapy. We expect the most efficient treatment effect by combining early Inhibition of necrosis and Inflammation followed by stimulating tubule regeneration. This project intends to turn acute tubular necrosis into a treatable disease.

急性肾小管坏死是急性肾损伤的重要临床表现。急性肾小管坏死患者仍然没有治愈的治疗选择，原因有很多。本项目旨在通过五个创新理念来克服这些限制：1。减少坏死性炎症。急性肾小管坏死损伤早期和晚期以细胞坏死和炎症为主。我们将首先确定在预先研究设计中已被证明有效的受调节细胞坏死、细胞因子和化学物质抑制剂的治疗窗口。2. 促进肾脏内在再生。肾元损失是由于肾小管再生不足造成的。我们将首先确定促再生化合物的治疗窗口期。3克隆小管细胞增殖？有多少坏死的小管细胞真的被存活的小管细胞的增殖所取代是未知的。我们将使用克隆增殖的谱系追踪来首先回答这个问题。4. 肾元损失决定长期预后。急性肾小管坏死后是肾再生还是肾萎缩取决于不可逆损失的肾单位的数量。我们将量化肾单位损失，并将其作为所有治疗干预措施的主要终点。5. 序贯联合治疗。我们期望最有效的治疗效果是结合早期抑制坏死和炎症，然后刺激小管再生。该项目旨在将急性肾小管坏死转变为一种可治疗的疾病。