Glomerular Disease Tutorial Notes

Glomerular disease  Segmental means that only part of the involved glomerulus is affected (e.g. a lobule) Pathology correlations    Diseases with the same basic pathology have different clinical features at different stages in their development However, diseases with different basic pathology can have similar clinical presentation, where often a biopsy is required to tell them apart Diseases which look the same by light microscopy may have different aetiologies and pathological mechanisms. Sometimes, the use of immunofluorescence, electron microscopy or the detection of circulating antibodies can provide a clue as to the specific pathology. Clinical presentations  There can be urinary abnormalities, such as proteinuria, haematuria and casts. It can result in either nephritic or nephrotic syndrome, with systemic effects including hypertension, amongst others. It can also lead to acute or chronic renal failure.  When investigating glomerular disease, the biggest problem is that the kidneys are physically inaccessible and the nephrons are too small for diagnostic imaging. Thus, the current approach is to observe urinary abnormalities, blood chemistry, immunology and renal biopsy Pathology of primary glomerular disease With cellular reaction:  Acute diffuse proliferative glomerulonephritis: Characterised histologically by diffuse proliferation of glomerular cells, associated with influx of leukocytes. The lesions are typically caused by immune complexes. The most common underlying infections are streptococcal o Clinical presentation: haematuria, nephritic syndrome o Light microscopy: endocapillary proliferation and polymorphs o Immunofluorescence: C3 and IgG – coarse granular o Electron microscopy: sub-epithelial ‘humps’  Mesangial proliferative glomerulonephritis o Clinical presentation: haematuria o Light microscopy: mesangial proliferation only o Immunofluorescence: IgA with or without others, forming coarse “comma shapes” o Electron microscopy: paramesangial deposits  Membrano-proliferative glomerulonephritis: Characterised by histological alterations in the glomerular basement membrane, proliferation of glomerular cells and leukocyte infiltration o Clinical presentation: haematuria, proteinuria, nephrotic syndrome, hypertension o Light microscopy: double contours (type I) o Immunofluorescence: C3 only – coarse granular o Electron microscopy: type I shows mesangial interposition subendothelial deposits while type II shows dense deposit disease  Focal and segmental glomerulonephritis: Characterised by sclerosis of some, but not all, glomeruli. Furthermore, in the affected glomeruli, only a portion of the capillary tuft is involved. It is the epithelial damage that is the hallmark of FSGN o Clinical presentation: haematuria, proteinuria o Light microscopy: segmental proliferation, necrosis o Immunofluorescence: IgA with or without other OR no IgA but various others including linear IgG  o Electron microscopy: various, often none-specific Crescentic glomerulonephritis: The crescents in the glomeruli are produced by the proliferation of the parietal epithelial cells lining Bowman’s capsule and by the infiltration of monocytes and macrophages. The main form of Crescentic glomerulonephritis is due to anti-basement membrane antibody o Clinical presentation: haematuria, proteinuria, hypertension and renal failure o Light microscopy: extracapillary proliferation (“crescent formation”) o Immunofluorescence: fibrin in crescent with or without other various substances o Electron microscopy: defects in capillary walls Without cellular reaction:  ‘Minimal change’ disease: This is the most frequent cause of nephrotic syndrome in children, characterised by diffuse effacement of the foot processes of the podocytes in glomeruli that appear virtually normal by light microscopy. It usually has a dramatic response to corticosteroid treatment o Clinical presentation: heavy proteinuria, nephrotic syndrome (steroid sensitive) o Light microscopy: nil or mild mesangial increase o Immunofluorescence: nil or IgM with or without C3 mesangium o Electron microscopy: effacement (fusion) of foot processes, podocyte swelling  Focal and segmental sclerosis and hyalinosis o Clinical presentation: heavy proteinuria, nephrotic syndrome (steroid sensitive) and renal failure o Light microscopy: segmental mesangial increase, PAS-positive masses (hyalinosis) o Immunofluorescence: IgM with or without C3 segmental o Electron microscopy: same as LM , and effacement of foot processes in LM normal areas  Membranous nephropathy: This is a common cause of nephrotic syndrome in adults. It is characterised by diffuse thickening of the glomerular capillary walls due to the accumulation of electron-dense, Igcontaining deposits along the subepithelial side of the basement membrane. Can be caused by drugs, underlying malignant tumours, SLE and infections. o Clinical presentation: heavy proteinuria, nephrotic syndrome o Light microscopy: thick capillary walls, deposits, basement membrane “spikes” o Immunofluorescence: IgG, C3 and other granular capillary walls o Electron microscopy: multiple subepithelial deposits, spokes and foot process loss  ‘Thin basement membrane disease’: This is a fairly common hereditary entity manifested clinically by familial asymptomatic haematuria. The abnormally thin basement membrane has been traced to mutations in the genes encoding for type IV collagen. o Clinical presentation: relatively benign condition, with only haematuria o Light microscopy: normal o Immunofluorescence: nil o Electron microscopy: abnormally thin basement membrane