Pathology of Glomerular Diseases

The glomerulus may be injured by several mechanisms but has only a limited number of histopathologic responses; accordingly, different disease states may produce similar microscopic changes.

Proliferation of glomerular cells occurs in most forms of glomerulonephritis and may be generalized, involving all glomeruli, or focal, involving only some glomeruli while sparing others. Within a single glomerulus, proliferation may be diffuse, involving all parts of the glomerulus, or segmental, involving only some areas but not others. Proliferation commonly involves the endothelial and mesangial cells and is frequently associated with an increase in the mesangial matrix (see Fig. 508-7 ). Mesangial proliferation may result from immune complex deposition within the mesangium. The resultant increase in cell size and number and in mesangial matrix may increase glomerular size and narrow the lumens of glomerular capillaries, leading to renal insufficiency.

Crescent formation in Bowman's space (capsule) is a result of proliferation of parietal epithelial cells. Crescents develop in several forms of glomerulonephritis (termed rapidly progressive) and are thought to be a response to fibrin deposited in Bowman's space. New crescents contain fibrin, the proliferating epithelial cells of Bowman's space, basement membrane-like material produced by these cells, and macrophages that may have a role in the genesis of glomerular injury. In days to weeks, the crescent is invaded by connective tissue (fibroepithelial crescent); this generally results in glomerular obsolescence. Crescent formation is frequently associated with glomerular cell death. The necrotic glomerulus has a characteristic eosinophilic appearance and usually contains nuclear remnants. Crescent formation is usually associated with generalized proliferation of the mesangial cells and with either immune complex or anti-GBM antibody deposition in the glomerular capillary wall.

Certain forms of acute glomerulonephritis show glomerular exudation of blood cells, including neutrophils, eosinophils, basophils, and mononuclear cells. The thickened appearance of GBM may result from a true increase in the width of the membrane (as seen in membranous glomerulopathy), from massive deposition of immune complexes that have staining characteristics similar to the membrane (as seen in systemic lupus erythematosus), or from the interposition of mesangial cells and matrix into the subendothelial space between the endothelial cells and the GBM. The latter may give the basement membrane a split appearance, as seen in type I membranoproliferative glomerulonephritis and other diseases.

Sclerosis refers to the presence of scar tissue within the glomerulus. Occasionally, pathologists use this term to refer to an increase in mesangial matrix.Tubulointerstitial fibrosis is present in all patients with glomerular disease who develop progressive renal injury. This fibrosis is initiated by injury to the renal tubules, resulting in mononuclear cell infiltrates that release soluble factors that have fibrosis-promoting effects. Additionally, matrix proteins of the renal interstitium begin to accumulate, leading to eventual destruction of renal tubules and peritubular capillaries. The actual transformation of tubular epithelium to mesenchymal tissue may contribute to progressive tubulointerstitial fibrosis.