Pathology Of Secondary Glomerular Disease

Pathology of secondary glomerular disease With cellular reaction:  Systemic lupus erythematosus (SLE): a systemic autoimmune disease involving multiple autoantibodies – antinuclear factor, anti-double stranded DNA. Affects multiple tissues/organs (kidney, skin, joints, blood, small vessels) o Clinical presentation: haematuria, proteinuria, nephrotic syndrome, renal failure and extra-renal symptoms o Light microscopy: various changes; 5 classes but often not proliferative, with/out necrosis, with/out various deposits o Immunofluorescence: IgG, IgA, IgM, C1q, C4, C3 deposits in the mesangium and capillaries o Electron microscopy: deposits and “microtubules”  Microscopic polyangiitis (MPA) group: this encompasses a group of systemic autoimmune diseases, including small vessel vasculitis and solid tissue involvement in Wegener’s granulomatosis. The main auto-antibody is anti-neutrophilic cytoplasmic antibody (ANCA) and this disease affects multiple tissues/organs. In Wegener’s granulomatosis, the main effects include local tissue destruction, especially in the respiratory tract, but also at other sites such as small vessel vasculitis in the kidneys and skin. There may also be necrotising glomerulonephritis o Clinical presentation: haematuria, proteinuria, renal failure and extra-renal manifestations (especially in the lungs) o Light microscopy: necrotising glomerular lesions (segmental to crescentic), no deposits o Immunofluorescence: “Pauci-immune”, with only fibrin, no immunoglobulin o Electron microscopy: no distinctive features  Anti-basement membrane disease (“Goodpasture’s syndrome”): this includes systemic autoimmune diseases such as capillaritis, with multiple tissue/organ involvement (kidneys, lung alveolar capillaries and retinas). The auto-antibodies are usually against the NC1 domain of the α3 chain of type IV collagen. This is found in many basement membranes, but is seen especially in the shared endothelium and epithelium o Clinical presentation: haematuria, proteinuria, renal failure, extrarenal manifestations (esp lungs) o Light microscopy: necrotising glomerular lesions (segmental to crescentic), no deposits o Immunofluorescence: linear fluorescent staining of the glomerular basement membrane o Electron microscopy: no distinctive features  Henoch-Schönlein purpura: this is a systemic immune-complex disease, involving post-infectious streptococcus, Bartonella and varicella. Multiple tissues/organs are involved e.g. skin leucocytoclastic vasculitis – purpura, gastrointestinal bleeding, arthropathy, heart, central nervous system, and kidneys Clinical presentation: haematuria, proteinuria, renal failure, extrarenal manifestations (esp in the skin, joints and GIT) o Light microscopy: glomerular lesions (proliferative – segmental, diffuse and crescentic) o Immunofluorescence: mesangial deposition of IgA, IgM, C3 and fibrin o Electron microscopy: electron-dense mesangial deposits Glomerular disease with bacterial endocarditis and infected “shunts”: this is an immune complex disease that is secondary to lowgrade infection in the cardiovascular system. Multiple tissues/organs are involved e.g. heart valves, coincidental systemic embolism with infarction, small haemorrhages, kidney lesions o Clinical presentation: haematuria, proteinuria, nephritic syndrome and impaired renal function o Light microscopy: various glomerular lesions – mesangial proliferation, membranoproliferative, focal and segmental, diffuse proliferative, crescentic o Immunofluorescence: deposition of IgG and C3 at various sites o Electron microscopy: electron-dense deposits at various sites o  Without cellular reaction:  Diabetic glomerulosclerosis: principal effects of diabetes on kidneys are – atherosclerosis of large renal arteries, secondary athero-embolism, severe infection pyelonephritis, renal medullary necrosis, glomerulosclerosis) o Clinical presentation: proteinuria, nephrotic syndrome, hypertension and renal failure o Light microscopy: nodules in the mesangium or diffuse mesangial increase, exudative lesions as well as afferent and efferent arteriosclerosis o Immunofluorescence: non-specific (many proteins) o Electron microscopy: thick glomerular basement membrane  Amyloidosis: this is a systemic disorder which involves the deposition in many sites of an abnormal fibrillar protein – physically all β-pleated sheet. There are chemically diverse types e.g. e.g. acute phase protein in chronic inflammations, and immunoglobulin light chains. The most common sites are the small blood vessels (including the glomerular capillaries), as well as the interstitial connective tissue (e.g. in the heart) o Clinical presentation: proteinuria, nephrotic syndrome, renal failure and several extra-renal manifestations o Light microscopy: thick glomerular basement membrane and mesangium, congo-red positive o Immunofluorescence: various changes, positive for Ig light chains o Electron microscopy: characteristic beaded fibrils  Hereditary nephropathies