Licht Christoph, Fremeaux-Bacchi Veronique
The Hospital for Sick Children, Division of Nephrology, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8.
Thromb Haemost. 2009 Feb;101(2):271-8.
Membranoproliferative glomerulonephritis (MPGN) is a chronic progressive renal disease that is diagnosed on the basis of renal histological features. Several MPGN subtypes have been defined by the localization and composition of glomerular deposits (electron dense, Ig and C3). MPGN II or dense deposit disease (DDD) which is defined by the occurrence of electron dense deposits within the lamina densa of the glomerular basement membrane (GBM) is strongly associated with dysregulation of the alternative complement pathway (AP). However, C3 Nephritic Factor (C3NeF), an autoantibody against the alternative C3 convertase C3bBb, and mutations in regulatory proteins of the AP have also been identified in other subtypes of MPGN and even in glomerulonephritis with mesangial C3 deposits. Clinically, MPGN is characterized by proteinuria (up to nephrotic range) and hypertension, frequent progression to end-stage kidney disease and disease recurrence after renal transplantation. The age of onset varies from childhood to adulthood. In the following we will review our current knowledge of pathogenesis of MPGN and will present a novel classification system of the disease based on pathogenesis rather than on morphology. A better understanding of the pathogenesis of MPGN is crucial for the development of novel, specific treatment strategies.
膜增生性肾小球肾炎（MPGN）是一种慢性进行性肾脏疾病，根据肾脏组织学特征进行诊断。几种MPGN亚型已根据肾小球沉积物（电子致密物、免疫球蛋白和C3）的定位和组成来定义。MPGN II型或致密物沉积病（DDD）由肾小球基底膜（GBM）致密层内电子致密物沉积的出现所定义，与替代补体途径（AP）的失调密切相关。然而，C3肾炎因子（C3NeF），一种针对替代C3转化酶C3bBb的自身抗体，以及AP调节蛋白的突变也已在MPGN的其他亚型中被发现，甚至在具有系膜C3沉积的肾小球肾炎中也有发现。临床上，MPGN的特征是蛋白尿（可达肾病范围）和高血压，频繁进展为终末期肾病以及肾移植后疾病复发。发病年龄从儿童期到成年期不等。在接下来的内容中，我们将综述我们目前对MPGN发病机制的认识，并将基于发病机制而非形态学提出一种新的疾病分类系统。更好地理解MPGN的发病机制对于开发新的、特异性治疗策略至关重要。
