Pathogenesis and treatment of glomerulonephritis-an update

Abstract This review updates current concepts of the genetic risk factors, etiologic events, nephtitogenic responses and treatment of the major immunologically mediated types of glomerulonephritis (GN). These include post-infectious GN, IgA nephropathy, anti-glomerular basement membrane (GBM) antibody disease, ANCA-associated vasculitis (AAV) and lupus nephritis. Although the etiology(s) of most GNs remain undefined, many are now believed to be initiated by environmental insults, particularly infectious processes, that trigger host responses in genetically susceptible individuals which lead to GN. Mechanistic concepts of these diseases have evolved from earlier views that most were consequent to glomerular trapping of preformed immune complexes to the current view that most of these diseases are auto-immune in nature mediated by both antibodies and T cells reactive with self-antigens. Therapy of GN has lagged behind advances in understanding pathogenesis. Newly appreciated roles for older mediators like complement and complement regulatory proteins offer new therapeutic targets.

摘要 本综述更新了当前学界对主要免疫介导型肾小球肾炎（glomerulonephritis, GN）的遗传危险因素、病因事件、致肾炎应答及治疗方案的认知。此类肾炎涵盖感染后肾小球肾炎、IgA肾病、抗肾小球基底膜（glomerular basement membrane, GBM）抗体病、抗中性粒细胞胞浆抗体相关性血管炎（antineutrophil cytoplasmic antibody-associated vasculitis, AAV）与狼疮性肾炎。尽管多数肾小球肾炎的病因仍未明确，但目前认为诸多病例由环境刺激（尤以感染过程为甚）诱发，在遗传易感个体中触发宿主应答，进而引发肾小球肾炎。此类疾病的机制认知已从早期"多数因预形成免疫复合物沉积于肾小球所致"的观点，转变为当前共识：多数此类疾病本质为自身免疫性疾病，由针对自身抗原的抗体与反应性T细胞共同介导。肾小球肾炎的治疗仍滞后于发病机制研究的进展，新近被阐明的补体及补体调节蛋白等经典介质的新作用，为该类疾病提供了全新的治疗靶点。