Rostoker G
Service de Néphrologie, Hôpital Privé Claude Galien, Quincy sous Senart, France.
BioDrugs. 1998 Apr;9(4):279-301. doi: 10.2165/00063030-199809040-00003.
IgA nephropathy is the commonest form of glomerulonephritis worldwide, and is one of the major causes of terminal renal failure in most industrialised countries. It is defined by the dominance of IgA mesangial deposits in immunofluorescence studies. Corticosteroid-sensitive nephrosis lipoides (minimal change disease) with IgA deposits and superimposed crescentic glomerulonephritis are to be differentiated from primary IgA nephropathy (Berger's disease). In the latter, clinical manifestations are dominated by synpharyngitic macroscopic haematuria and permanent proteinuria. Terminal renal failure occurs in about 25% of patients after 10 years or more. Heavy proteinuria, hypertension, altered renal function and severe histological lesions at diagnosis are markers of poor prognosis. Primary IgA nephropathy is thought to be related to mesangial deposition of polymeric IgA1-containing immune complexes, owing to altered B cell responses to exogenous and endogenous antigens, together with hyperactivity of T helper type 1 and type 2 cells, both favoured by a genetic background. The 2 compartments of the IgA system (medullary and mucosal) may participate in the pathogenesis of the disease. Modulation of gut-associated lymphoid tissue and immune tonsillectomy are current lines of research. Although impressive results were obtained with an oligoantigenic diet, it is somewhat impractical. Pharmacological modulation of the mucosal immune response seems more promising. There is no proof that phenytoin, a drug which reduces bone marrow IgA synthesis, is beneficial. Emerging data suggest the potential of immune intervention in severely proteinuric patients before sclerotic lesions have occurred, using azathioprine and intravenous immunoglobulins. The benefit of early corticosteroid therapy is still unknown in both adults and children, and the efficiency of alkylating agents is unproven. The search for bacterial foci in primary IgA nephropathy is mandatory, as appropriate treatment may have a protective effect on renal function and help to improve or stabilise some patients. Slowing the progression of renal failure by a combination of ACE inhibitors, fish oil and, possibly, antiplatelet drugs is a promising therapeutic approach.
IgA肾病是全球最常见的肾小球肾炎类型，也是大多数工业化国家终末期肾衰竭的主要原因之一。它在免疫荧光研究中由IgA系膜沉积物占主导来定义。需将伴有IgA沉积的皮质类固醇敏感性类脂性肾病（微小病变病）和叠加的新月体性肾小球肾炎与原发性IgA肾病（伯杰病）区分开来。在后者中，临床表现以咽炎后肉眼血尿和持续性蛋白尿为主。约25%的患者在10年或更长时间后会出现终末期肾衰竭。诊断时出现大量蛋白尿、高血压、肾功能改变和严重的组织学病变是预后不良的标志。原发性IgA肾病被认为与含多聚IgA1免疫复合物的系膜沉积有关，这是由于B细胞对外源性和内源性抗原的反应改变，以及1型和2型辅助性T细胞的过度活跃，而这两者都受到遗传背景的影响。IgA系统的两个部分（髓质和黏膜）可能参与了该疾病的发病机制。对肠道相关淋巴组织的调节和免疫扁桃体切除术是当前的研究方向。尽管低抗原饮食取得了令人瞩目的结果，但它在某种程度上不切实际。对黏膜免疫反应的药物调节似乎更有前景。没有证据表明可减少骨髓IgA合成的药物苯妥英有益。新出现的数据表明，在硬化性病变出现之前，对严重蛋白尿患者使用硫唑嘌呤和静脉注射免疫球蛋白进行免疫干预具有潜力。早期皮质类固醇治疗对成人和儿童的益处仍不明确，烷化剂的疗效也未经证实。在原发性IgA肾病中寻找细菌病灶是必要的，因为适当的治疗可能对肾功能有保护作用，并有助于改善或稳定部分患者的病情。联合使用血管紧张素转换酶抑制剂、鱼油以及可能的抗血小板药物来减缓肾衰竭的进展是一种有前景的治疗方法。
