Couser W G
Department of Medicine, University of Washington, Seattle 98195.
Am J Kidney Dis. 1988 Jun;11(6):449-64. doi: 10.1016/s0272-6386(88)80079-9.
Immunopathologic studies over the past two decades have demonstrated that rapidly progressive glomerulonephritis (RPGN) can result from glomerular deposition of anti-GBM antibody, immune complexes, or from some as yet undefined mechanism that does not involve glomerular antibody deposition. The latter process may be cell mediated and resembles a small vessel vasculitis. Most cases of idiopathic RPGN are not accompanied by pathogenic glomerular immunoglobulin deposition. Recent experimental studies of immune mechanisms of glomerular injury have identified several new processes that can induce damage to the capillary wall sufficient to result in crescentic glomerulonephritis (GN). These include direct effects of anti-GBM antibody alone and of the complement C5b-9 (membrane attack) complex, nephritogenic effects of inflammatory effector cells that involve reactive oxygen species and glomerular halogenation, and injury mediated by sensitized lymphocytes independently of antibody deposition. Macrophages have been shown to participate in both intracapillary and extracapillary fibrin deposition and crescent formation as well as to mediate capillary wall damage. The role of resident glomerular cells and cell-cell interactions in glomerulonephritis is still under active investigation. Despite these several advances in understanding immune injury to the glomerulus, therapy for RPGN remains largely empiric. Although the prognosis in RPGN has clearly improved over time, no form of disease-specific therapy has been clearly shown yet to be beneficial in a controlled study. Interpretation of the existing literature on therapy is complicated by the availability of only historical rather than concurrent controls, lack of attention to several variables known to affect disease outcome, and uncertainty regarding bias in favor of reporting positive results. Available data suggests that optimal outcomes may be achieved in anti-GBM nephritis by treatment with steroids, immunosuppression and plasma exchange, particularly when therapy is directed at patients with mild but rapidly progressive disease before oliguria or severe azotemia develop. Pulse steroids are probably the most cost-effective therapy for the idiopathic form of RPGN, but treatment with cytotoxic agents should be considered if clinical or histologic evidence of vasculitis is present.
过去二十年的免疫病理学研究表明，快速进展性肾小球肾炎（RPGN）可由抗肾小球基底膜（GBM）抗体、免疫复合物在肾小球沉积引起，或由某些尚未明确的、不涉及肾小球抗体沉积的机制所致。后一过程可能是细胞介导的，类似于小血管血管炎。大多数特发性RPGN病例并无致病性肾小球免疫球蛋白沉积。最近关于肾小球损伤免疫机制的实验研究发现了几个新过程，这些过程可诱导对毛细血管壁的损伤，足以导致新月体性肾小球肾炎（GN）。这些过程包括单独的抗GBM抗体和补体C5b - 9（膜攻击）复合物的直接作用、涉及活性氧和肾小球卤化的炎性效应细胞的致肾炎作用，以及致敏淋巴细胞独立于抗体沉积介导的损伤。巨噬细胞已被证明参与毛细血管内和毛细血管外纤维蛋白沉积及新月体形成，并介导毛细血管壁损伤。肾小球固有细胞和细胞间相互作用在肾小球肾炎中的作用仍在积极研究中。尽管在理解肾小球免疫损伤方面有了这几个进展，但RPGN的治疗在很大程度上仍基于经验。尽管随着时间推移RPGN的预后明显改善，但在对照研究中尚未明确显示任何形式的疾病特异性治疗有益。现有治疗文献的解读因仅有历史对照而非同期对照、未关注几个已知影响疾病结局的变量以及报告阳性结果时存在偏倚的不确定性而变得复杂。现有数据表明，对于抗GBM肾炎，通过使用类固醇、免疫抑制和血浆置换治疗可能取得最佳结果，特别是当治疗针对在少尿或严重氮质血症发生前患有轻度但快速进展性疾病的患者时。脉冲类固醇可能是特发性RPGN最具成本效益的治疗方法，但如果存在血管炎的临床或组织学证据，则应考虑使用细胞毒性药物治疗。
