Anti-Glomerular Basement Membrane Disease

Abstract

Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals. The majority of patients develop widespread glomerular crescent formation, presenting with features of rapidly progressive GN, and 40%-60% will have concurrent alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody, typically with the use of plasma exchange, along with steroids and cytotoxic therapy to prevent ongoing autoantibody production and tissue inflammation. Retrospective cohort studies suggest that when this combination of treatment is started early, the majority of patients will have good renal outcome, although presentation with oligoanuria, a high proportion of glomerular crescents, or kidney failure requiring dialysis augur badly for renal prognosis. Relapse and recurrent disease after kidney transplantation are both uncommon, although de novo anti-GBM disease after transplantation for Alport syndrome is a recognized phenomenon. Copresentation with other kidney diseases such as ANCAassociated vasculitis and membranous nephropathy seems to occur at a higher frequency than would be expected by chance alone, and in addition atypical presentations of anti-GBM disease are increasingly reported. These observations highlight the need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, particularly for patients presenting with adverse prognostic factors.

Clustering of Anti-GBM Disease: Clues to an Environmental Trigger?

“…It is assumed that similar pathogenic mechanisms are involved in other autoimmune diseases, although few are so well delineated as in this example. In antiglomerular basement membrane (anti-GBM) disease, the components of the aberrant adaptive immune response that are involved in disease pathogenesis are clearly described, such as pathogenic autoantibodies directed to a well defined autoantigen supported by a population of autoreactive T cells (2,3). The putative environmental triggers, however, and how they interact with the known genetic determinants of disease susceptibility to initiate this aberrant response are not fully understood.…”

The role of plasma exchange in the management of autoimmune disorders

“…Although anti-GBM disease has a very poor prognosis without adequate therapy, it responds well to treatment and relapses are uncommon (McAdoo & Pusey, 2017).…”

Management of Elderly Patients with Rapidly Progressive Glomerulonephritis

“…Unlike AAV, anti-GBM disease typically displays bimodal age distribution with the peak incidence reached in the third decade (often presenting as pulmo-renal syndrome) and then in the sixth and seventh decades (when isolated kidney involvement is more common) [10]. …”