KFO 228: Immunopathogenesis and Therapy of Glomerulonephritis

肾小球肾炎作为一种疾病类别是西方世界终末期肾脏疾病的主要原因之一，并与发病率和死亡率增加有关。快速进行性肾小球肾炎（RPGN）是肾小球肾炎最具侵袭性、临床预后最差的形式。它代表了疾病实体的异质集合。然而，每种形式的RPGN的基础是免疫介导的肾损害，包括特异性免疫反应，随后是炎症的效应期。这一病理生理学概念是目前使用皮质类固醇和细胞毒性药物进行非特异性免疫抑制治疗的基本原理。然而，这些治疗方案缺乏特异性，以及经常致残的副作用是迫切需要开发新的和更具体的个体治疗策略的主要原因。该临床研究单位将汇集在人类和实验肾小球肾炎、细胞免疫学和肾脏病理学方面具有强大专业知识的科学家。利用最先进的技术和（转基因）动物模型，结合对RPGN患者的大型队列前瞻性研究，该临床研究单元旨在更好地了解增殖性和新月形肾小球肾炎的免疫发病机制。细胞介导的免疫反应在肾脏疾病的发生和进展中的作用将是主要的焦点。这些实验方法将确定、表征和验证新的诊断、预后和治疗靶点，从而为人类肾小球肾炎提供更具体、毒性更小的治疗。

Glomerulonephritis as a disease category is one of the leading causes of end-stage renal disease in the Western world and is associated with increased morbidity and mortality. The most aggressive form of glomerulonephritis with the worst clinical outcome is rapidly progressive glomerulonephritis (RPGN). It represents a heterogeneous collection of disease entities. However, fundamental to each form of RPGN is the immune-mediated renal damage that consists of a specific immune reaction followed by an effector phase of inflammation. This pathophysiological concept is the current rationale for unspecific immunosuppressive therapy with corticosteroids and cytotoxic agents. The missing specificity of these therapeutic regimes, however, and the frequently disabling side effects are the main reasons for the urgent need to develop new and more specific individual therapeutic strategies. This Clinical Research Unit will bring together scientists with strong expertise in human and experimental glomerulonephritis, in cellular immunology and in renal pathology. Using state-of-the-art techniques and (transgenic) animal models, combined with prospective studies in a large cohort of patients with RPGN, this Clinical Research Unit seeks to better understand the immunopathogenesis of proliferative and crescentic glomerulonephritis. The contribution of cell-mediated immune responses in the development and progression of renal disease will be the main focus. These experimental approaches will identify, characterise and validate new diagnostic, prognostic and therapeutic targets for a more specific and less toxic treatment of human glomerulonephritis.