Tomino Yasuhiko
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Contrib Nephrol. 2013;181:65-74. doi: 10.1159/000348457. Epub 2013 May 8.
IgA nephropathy (IgAN) is characterized by the expansion of the glomerular mesangial matrix with mesangial cell proliferation and/or mononuclear cell infiltration. Glomeruli typically contain generalized diffuse granular mesangial deposits of IgA (mainly galactose-deficient polymeric IgA1), IgG and C3. Electron-dense deposits are observed in the glomerular mesangial area and glomerular basement membrane. Therefore, this disease is considered to be an immune complex-mediated glomerulonephritis. The detailed observations of electron-dense deposits are of value for the evaluation of the disease activity. The evidence- and lumped-system-based histological classification can identify the magnitude of the risk of disease progression and is useful for predicting long-term renal outcome in this disease. A study of IgAN patients showed that the number of angiotensin-II-positive cells was correlated with mast cells containing both tryptase and chymase and containing only tryptase in the interstitial lesions with the most severe pathological changes. Hypercomplementemia occurs in the progression of IgAN and is controlled by an increase of complement regulatory proteins. The measurement of urinary levels of membrane attack complex and factor H and extraglomerular C3 deposition could be useful indicators of renal injury in patients with IgAN. Development of glomerulosclerosis in IgAN patients is associated with podocytopenia and the alteration of the podocyte components, i.e. podocalyxin and dendrin. It appears that the number of urinary podocytes and levels of urinary podocalyxin are useful for predicting histological changes in IgAN patients. A positive correlation was observed between acute extracapillary changes and the number of dendrin-positive nuclei per glomerulus in patients with IgAN. It is concluded that there are many immunopathological predictors of prognosis, including genetic background, in this disease. Thus, the early diagnostic screening of prognosis predictors and subsequent intervention are important for the good prognosis in this disease.
IgA肾病(IgAN)的特征是肾小球系膜基质扩张,伴有系膜细胞增殖和/或单核细胞浸润。肾小球通常含有IgA(主要是缺乏半乳糖的聚合IgA1)、IgG和C3的弥漫性颗粒状系膜沉积物。在肾小球系膜区和肾小球基底膜可见电子致密沉积物。因此,该疾病被认为是一种免疫复合物介导的肾小球肾炎。对电子致密沉积物的详细观察对评估疾病活动具有重要价值。基于证据和集总系统的组织学分类可以确定疾病进展风险的大小,有助于预测该疾病的长期肾脏预后。一项对IgAN患者的研究表明,在病理变化最严重的间质病变中,血管紧张素II阳性细胞的数量与同时含有类胰蛋白酶和糜蛋白酶以及仅含有类胰蛋白酶的肥大细胞相关。IgAN进展过程中会出现补体血症升高,且受补体调节蛋白增加的控制。测量尿中膜攻击复合物、因子H水平以及肾小球外C3沉积可能是IgAN患者肾损伤的有用指标。IgAN患者肾小球硬化的发展与足细胞减少以及足细胞成分(即足细胞表面蛋白和树突蛋白)的改变有关。尿足细胞数量和尿足细胞表面蛋白水平似乎有助于预测IgAN患者的组织学变化。在IgAN患者中,急性毛细血管外变化与每个肾小球中树突蛋白阳性核的数量之间存在正相关。得出的结论是,在这种疾病中,包括遗传背景在内,有许多免疫病理预后预测指标。因此,对预后预测指标进行早期诊断筛查并随后进行干预对于该疾病的良好预后很重要。