Rapidly progressive glomerulonephritis (RPGN) is a syndrome associated with severe glomerular injury, but does not denote specific etiologic form of glomerulonephritis
It is characterized by rapid and progressive loss of renal function associated with severe oliguria and signs of nephritic syndrome.
RPGN is classified into 3 groups depending upon immunologic findings
Anti GBM antibody mediated diseases characterized by linear deposits of IgG and in many cases C3 in the GBM. Eg. Good Pasteur syndrome
Disease caused by immune complex deposition eg. Post infectious glomerulonephritis, Lupus nephritis, IgA nephropathy and Henoch Schonlein Purpura
Pauci immune RPGN, defined by lack of detectable anti-GBM antibodies or immune complexes by immunofluorescence and electron microscopy eg. systemic vasculitis as in granulomatosis with polyangitis or microscopic polyangitis
90% of idiopathic cases have Anti neutrophil cytoplasmic antibodies.
Morphology –
Grossly kidneys are enlarged, pale with petechial hemorrhages on cortical surface
Microscopy
Glomeruli show focal and segmental necrosis, diffuse or focal endothelial cell proliferation and mesangial proliferation
Segmental glomerular necrosis with adjacent uninvolved glomerular segments is a feature of pauci immune RPGN.
Crescent formation is the characteristic histologic picture
Crescents are formed by proliferation of parietal cells and by migration of monocytes and macrophages into the Bowmans space. Neutrophils and lymphocytes may be present.
Crescents may obliterate the urinary space and compress the glomerular tufts. Fibrin strands are frequently prominent between the cellular layers of crescent
The escape of procoagulant factors, fibrin and cytokines into Bowmans space may contribute to crescent formation
As the crescent enlarges, it compresses the glomerular tufts and later the tuft collapses. Most of the crescents undergo organization and focal segmental necrosis which resolves as segmental scars.Finally the collagen is laid down and entire glomerulus is replaced by fibrous tissue.
Without treatment disease progresses to end stage renal failure in weeks or months
Immunofluorescence microscopic features
Immune complex-mediated cases show granular immune deposits
Good Pasteur syndrome cases show linear GBM fluorescence for immunoglobulin and complement
Pauci immune cases have little or no deposition of immune reactants
Electron microscopy
Shows ruptures in the GBM that allows leukocytes, plasma proteins such as coagulation factors, complement factors and inflammatory mediators to reach urinary space where they trigger crescent formation.
References
Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. The Kidney. In: Robbins and Cotran Pathologic basis of disease. 8th edition.
