Focal Proliferative GN

• Focal proliferative pattern of glomerular injury consists of endocapillary or extracapillary (crescents) proliferative changes that occur in segmental or global fashion and involve less than 50% of all glomeruli.

• The process can be pauci-immune, most commonly associated with ANCA. A number of immune complex-mediated processes can lead to this pattern of injury, such as lupus nephritis (class III) or IgA nephropathy.

• Pauci-immune GN• Lupus Class III• IgA

• Pauci-immune GN– As in crescentic GN

Lupus Nephritis Class III• Histopathology: • Light microscopic examination reveals segmental or global

endocapillary proliferative changes. The mesangium is usually expanded and hypercellular

• The peripheral capillary loops are irregular in thickness, sometimes showing 'wire loops' and intraluminal 'microthrombi' (hyaline thrombi)

• Leukocyte infiltration, focal necrosis, hematoxilin bodies, and cellular crescents can all be seen

• In some cases, membranoproliferative pattern of injury may be dominant in glomeruli (class IV)

• The tubulointerstitium may show active interstitial nephritis

• Immunofluorescence: • There is 'full house' reactivity (reactivity for IgG, IgM, and IgA), with

granular deposits in the mesangium.

• Electron microscopy: • Visceral epithelial cells: Show different degrees of injury and

degenerative changes, with focal, but sometimes extensive, effacement of foot processes. Subepithelial deposits can be seen in many cases

• Glomerular basement membranes: May be irregular in thickness, with the presence of intramembranous, subepithelial, and/or subendothelial deposits. Subendothelial deposits can be rather large and may demonstrate substructural organization ('fingerprint'-like pattern)

• Glomerular endothelial cells: May contain tubuloreticular structures

• Mesangium: Expanded by increase in cellular elements and extracellular matrix, with sometimes large and confluent fine granular, electron-dense deposits

IgA• Histopathology: • Light microscopic examination reveals mesangial hypercellularity and

expansion of mesangial matrix, with segmental or global endocapillary proliferation and/or crescent formation

• If the number of involved glomeruli is below 50 percent, it is designated as focal proliferative pattern; if there are 50 percent or more glomeruli involved, the process is designated as diffuse proliferative IgA glomerulonephritis

• The tubulointerstitium may be unremarkable or show active inflammation or patchy fibrosis

• Immunofluorescence: • There is dominant reactivity for IgA in the mesangium; C3 may be

equally or less reactive. There is usually stronger reactivity for lambda than for kappa light chains in the mesangial deposits

• Electron microscopy: • Visceral epithelial cells: Show different degrees of injury and

degenerative changes; the effacement of foot processes is usually focal but sometimes extensive. Subepithelial and/or subendothelial deposits can also be present

• Glomerular basement membranes: May be thin; there is a higher incidence of thin glomerular basement membrane disease in IgA nephropathy than in any other glomerular disease {6}

• Glomerular endothelial cells: May show non-specific signs of injury; tubuloreticular structures are not seen

• Mesangium: Shows increase in cellularity and extracellular matrix, with fine granular electron-dense deposits that are sometimes large and confluent