Pulmonary-Renal Syndrome with a Focus on Anti-GBM Disease

Abstract

Pulmonary-renal syndrome is a potentially life-threatening combination of pulmonary hemorrhage and acute renal failure. Several pathological entities can cause this syndrome. This review discusses the diagnostic strategy required to initiate appropriate therapy. Rapid serological testing and appropriate interpretation can be of great additive diagnostic value. Also discussed are the pathogenesis, therapy, and outcome of anti-glomerular basement membrane disease, one of the pathological entities that can cause pulmonary-renal syndrome.

Basic and Translational Concepts of Immune-Mediated Glomerular Diseases

“…[84][85][86] Rapidly Progressive, Crescentic GN Anti-GBM Nephritis Anti-GBM nephritis is characterized initially by an acute, focal necrotizing GN with crescents and linear deposition of IgG, usually with C3, along the GBM. 87,88 When associated with pulmonary alveolar hemorrhage, it is called Goodpasture's syndrome. The role of anti-GBM antibody deposition inducing complement activation, chemotactic factor release, and neutrophil-mediated injury was defined in NTN models in the 1960s, 89 and the pathogenicity of human anti-GBM antibody was confirmed by the classic primate transfer studies of Lerner et al in 1967.…”

“…87,93,94 Antibodies with apparently similar reactivity (but with lower titers, lower avidity, and primarily of the IgG2 and IgG4 subclasses) can be present in healthy humans. 95 GBM antigens are also expressed in several extrarenal tissues where they are sequestered by an endothelial cell layer impermeable to IgG.…”

“…100 Pulmonary toxins such as infections, smoke, and volatile hydrocarbons may damage endothelium and expose antigen in alveolar capillaries accounting for the pulmonary manifestations in Goodpasture's syndrome. 87,96 Whether such extrarenal events have any role in autoimmunization is not known.…”

A False-positive Antineutrophil Cytoplasmic Antibody Proteinase 3 Test in a Patient with Pulmonary-renal Syndrome

“…Urgent serological support or refutation for ANCA directed against PR3 and myeloperoxidase or anti-GBM is of utmost importance in differentiating between systemic vasculitis and other underlying diseases and may lead to the appropriate administration of aggressive immunosuppressive therapy 1 . This case illustrates that false-positive serological results can, however, sporadically occur, and can lead to incorrect diagnosis and treatment.…”

“…Although all other symptoms in our patient could be consistent with GPA, the hyperbilirubinemia and thrombopenia were more suggestive for leptospirosis. Nevertheless, the medical team was misdirected by the positive dot-blot test for PR3 ANCA, because this result is very specific for the diagnosis of ANCA-associated vasculitis in a patient with pulmonary-renal syndrome 1 .…”