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INTRODUCTION

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ESSENTIALS OF DIAGNOSIS

  • Rapidly deteriorating renal function, with or without hemoptysis and pulmonary shadowing on chest radiograph characterizes this entity.

  • Hematuria and proteinuria on urine dipstick and erythrocyte casts and/or dysmorphic erythrocytes are often seen on urine microscopy.

  • Circulating antibodies directed against the glomerular basement membrane (GBM) are sometimes present.

  • Kidney biopsy often demonstrates focal necrotizing glomerulonephritis with linear deposition of immunoglobulin.

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GENERAL CONSIDERATIONS

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Anti-glomerular basement membrane (GBM) disease is a rare but uniquely well-defined form of glomerulonephritis characterized by pathogenic autoantibodies specific for a single component of the GBM—the NC1 domain of the α3 chain of type IV collagen [α3(IV)NC1]. The α3 chain is only expressed in a small number of other basement membranes most notably those of pulmonary alveoli, which explains why the kidney and lung are the principal organs targeted in this disease. Typically these autoantibodies cause severe focal necrotizing glomerulonephritis with crescents resulting in rapidly progressing renal failure; while lung injury is characterized by alveolar hemorrhage. These are the features classic anti-GBM disease that is overwhelmingly the most common form. However, exceptional patients with linear deposition of IgG antibodies along the GBM have more chronic forms of glomerulonephritis. Standard assays for anti-GBM antibodies in these patients are usually negative in these patients who have been termed atypical anti-GBM disease (although the name is controversial).

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The annual incidence of anti-GBM disease is between 1.5 and 2.5 cases per million population in the European caucasian, Japanese, and Chinese populations but it is exceptionally rare in those of African descent. Anti-GBM disease affects all age groups but is much less common in children and is more common in the third decade and the sixth or seventh decades. Lung hemorrhage is more common in younger patients, probably because of its close association with cigarette smoking. When this occurs, the condition has been known as Goodpasture disease but the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of vasculitides, which includes anti-GBM disease as a small vessel vasculitis, recommends the term be discontinued.

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KEY READINGS

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Glassock  RJ: Atypical anti-glomerular basement membrane disease: lessons learned. Clin Kidney J 2016;9:653.  [PubMed: 27679709]
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Jennette  JC  et al: 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65:1.  [PubMed: 23045170]

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PATHOGENESIS

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The autoimmune response in anti-GBM disease is focused on the α3(IV)NC1 domain of type IV collagen and the epitopes recognized by the patients’ autoantibodies and auto-reactive T cells are known. Susceptibility to the disease is strongly influenced by the HLA complex: HLA types DR15 (and to a lesser extent DR4) predisposes to disease whilst HLADR1 and DR7 confer dominant protection which at least in the case of DR1 is mediated by inducing antigen specific regulatory T cells that suppress the autoimmune response. Much less is known about the ...

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