Pathology overview and classification
The pathology manifests as a sharp drop in renal blood flow, glomerular filtration rate, and diuresis. Clinically, the process is accompanied by severe oliguria or anuria. Within several weeks or months, the process progresses to irreversible acute or chronic renal failure.
Depending on the origin and clinical course, 3 groups of RPGN are distinguished:
- Post-infectious (post-streptococcal) variant.
- In systemic diseases (e.g., systemic lupus erythematosus).
- Idiopathic (primary) variant, accounting for about half of all cases.
Mechanisms of development and forms
There is no single mechanism for all variants of the disease; pathogenesis directly depends on the specific form:
- Immune complex mechanism: characteristic of post-streptococcal forms and involvement in systemic lupus erythematosus.
- Antibody-mediated mechanism: a striking example is Goodpasture syndrome. Antibodies against the glomerular basement membrane are detected in the blood (>95% of cases), cross-reacting with alveolar basement membranes of the lungs and causing pulmonary hemorrhage. Immunohistochemistry reveals linear deposits of IgG and C3 complement along the basement membranes.
- Idiopathic RPGN: can be triggered by various pathways (immune complexes, anti-GBM antibodies, or ANCAs), and it is here that the most severe glomerular damage is observed.
Pathological anatomy: macroscopic and microscopic picture
At autopsy or upon kidney biopsy in RPGN, the kidneys are enlarged, pale, and petechial hemorrhages are visible on their surface.
Microscopic examination reveals focal necroses (including fibrinoid necrosis), as well as endothelial and mesangial cell proliferation. The main diagnostic criterion is the formation of cellular crescents:
- They form in Bowman's space due to the proliferation of parietal epithelial cells and the migration of macrophages and monocytes.
- Characteristic strands of fibrin are identified between the layers of cells.
- Enlarging, the crescents compress the glomerulus and completely obliterate Bowman's capsule.
Electron microscopy consistently records ruptures of the glomerular basement membrane, and in some patients, the presence of subepithelial deposits. Subsequently, the majority of crescents undergo sclerosis.
Briefly: answers to topical questions
What immunohistochemical pattern (fluorescence type) is characteristic of the immune complex variant of RPGN?
The immune complex variant of rapidly progressive glomerulonephritis is characterized by granular fluorescence on immunofluorescence microscopy. This immunohistochemical pattern results from the deposition of preformed circulating immune complexes (or their formation in situ) in the mesangium and glomerular capillary walls. This type of injury is associated with pathologies such as acute post-streptococcal glomerulonephritis, systemic lupus erythematosus, IgA nephropathy, Henoch-Schönlein purpura, cryoglobulinemia, and subacute infective endocarditis.
In which systemic diseases can secondary rapidly progressive glomerulonephritis develop?
Secondary rapidly progressive glomerulonephritis can develop against the background of a number of rheumatic and systemic autoimmune conditions. These pathologies include:
- Systemic lupus erythematosus — in severe lupus nephritis.
- Hemorrhagic vasculitis — presents as focal segmental proliferative or extracapillary glomerulonephritis.
- IgA nephropathy (Berger's disease) — in severe cases with crescent formation.
- Bacterial endocarditis — immune complex glomerulonephritis.
- Idiopathic mixed cryoglobulinemia — a systemic disease.
- Microscopic polyangiitis — a systemic vasculitis.
- Goodpasture syndrome — an antibody-mediated variant of injury.
What types of antineutrophil cytoplasmic antibodies (ANCAs) are detected in idiopathic RPGN?
In idiopathic rapidly progressive glomerulonephritis, two main types of antineutrophil cytoplasmic antibodies are detected, occurring with approximately equal frequency. These include:
- c-ANCA — antibodies to proteinase-3 (PR-3);
- p-ANCA — antibodies to myeloperoxidase (MPO).
These antibodies are characteristic of the pauci-immune variant of glomerular injury (pauci-immune), in which immune deposits are absent or minimal.
RPGN = Rapid Decline of Principal Nephro-function + Glomerular Crescents.
Class and exam questions
What is the main morphological marker of rapidly progressive glomerulonephritis?
The main morphological marker is the formation of epithelial crescents in the majority of renal glomeruli.
What is the basis of Goodpasture syndrome in RPGN?
It is based on an antibody-mediated mechanism with the circulation of anti-glomerular basement membrane antibodies that cross-react with lung alveoli and produce linear IgG deposits.
How do "crescents" form in the glomeruli?
They arise due to the proliferation of parietal capsule cells and the migration of monocytes and macrophages into Bowman's space, leading to compression of the glomerulus.
What else to study on this topic
- Pathogenesis of immune complex glomerulonephritis
- The role of ANCAs in idiopathic RPGN
- Ultrastructural changes and the role of deposits
- Differential diagnosis of extracapillary proliferation
- Outcomes and sclerosis of glomerular crescents
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