Glomerular Diseases Dependent on Complement Activation, Including Atypical Hemolytic Uremic Syndrome, Membranoproliferative Glomerulonephritis, and C3 Glomerulopathy: Core Curriculum 2015

Abstract

Complement is part of the innate immune system and plays a fundamental role in the clearance of immune complexes and cell debris. The main effector mechanisms of complement activation are induction of inflammatory response and phagocytosis and cell lysis. However, complement activation is a double-edged sword and has the potential to damage self-tissues. In order to avoid self-damage, there is an absolute need for strict control by fluid-phase and membrane-bound regulatory proteins. Thus, an underperforming regulatory system (due to either genetic or acquired abnormalities) can shift the balance between regulation and activation toward the latter and lead to tissue injury in response to otherwise innocuous stimuli. Deposition of both actived complement fragments from plasma in glomeruli and complement locally produced and activated in the kidney may contribute to many kidney disorders, including lupus nephritis, postinfectious glomerulonephritis, membranous nephropathy, antineutrophil cytoplasmic antibody vasculitis, and anti–glomerular basement membrane (anti-GBM) glomerulonephritis. Interest in the complement system has been boosted in the past 15 years by the discovery that rare devastating kidney diseases, including atypical hemolytic uremic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN), are disorders of complement regulation. Additional Readings » Nangaku M. Complement regulatory proteins in glomerular diseases. Kidney Int. 1998;54(5):1419-1428. » Ricklin D, Hajishengallis G, Yang K, et al. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785-797. » Thurman JM. Complement in kidney disease: core curriculum 2015. Am J Kidney Dis. 2015;65(1):156-168. » Vieyra MB, Heeger PS. Novel aspects of complement in kidney injury. Kidney Int. 2010;77(6):495-499.