The clinical manifestations of glomerular renal disease are apt to consist only of varying degrees of hematuria, excretion of characteristic formed elements in the urine, proteinuria, and renal insufficiency and its complications.
Excluding diabetes, purported immunologic renal diseases are the most common cause of proteinuria and the nephrotic syndrome.
Alterations in glomerular architecture as observed in tissue examined by light microscopy alone can be minimal, nonspecific, and difficult to interpret. For these reasons, specific diagnoses of renal disease require targeted immune fluorescent techniques for demonstrating a variety of antigens, antibodies, and complement fractions. Electron microscopy has complemented these immunologic methods. Tissue analysis can be assisted by blood tests of immunoglobulins (Ig), complement, and other mediators of inflammation.
The 2 important humoral mechanisms leading to deposition of antibodies within the glomerulus are based on the location of the antigen, whether fixed within the kidney or present in soluble form in circulation. The fixed antigens are either a natural structural element of the glomerulus or foreign materials that have been trapped within the glomerulus for a variety of immunologic or physiochemical reasons. The best examples of the fixed natural antigens are those associated with the glomerular basement membrane (GBM). These antigens are evenly distributed in the GBM and cause characteristic linear IgG deposition, as determined in immunofluorescence studies.
This process represents 5% of cases of immune-mediated glomerular disease and is referred to as anti-GBM disease.
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However, most patients with glomerular immune deposits have discontinuous immune aggregates caused by antibody binding to native renal cell antigens or to antigens trapped within the glomerulus. In addition, immune complexes formed in the circulation can deposit and accumulate in the GBM and the mesangium.
A group of immune-mediated nephritides characterized by necrotizing and crescentic architecture and rapid progression are referred to as pauci-immune glomerular nephritides because, while antibodies may contribute to the pathogenesis of the disease, they are rarely demonstrated within the glomeruli. These are known as antineutrophil cytoplasmic antibody (ANCA) diseases. Circulating antibodies against myeloperoxidase, MPO (P-ANCA) and proteinase 3, PR3 (C-ANCA) have been noted in microscopic angiitis and Wegener’s granulomatosis, respectively.
Cellular immune processes are likely to be stimulated and contribute in different ways in various other forms of glomerulonephritides.
The current classification of glomerulonephritis is based on the mechanism, the presence, and the localization of immune aggregates in the glomeruli.
Immunologic Mechanisms Likely
A. SUBEPITHELIAL IMMUNE DEPOSITS
1. Glomerulonephritis associated with postinfectious glomerulonephritis such as poststreptococcal glomerulonephritis
2. Membranous nephropathy idiopathic or secondary to other causes such as systemic lupus erythematosus, cancer, gold penicillamine
B. SUBENDOTHELIAL IMMUNE DEPOSITS
1. Glomerulonephritis associated with systemic lupus erythematosus, type I idiopathic membranoproliferative glomerulonephritis (MPGN), glomerulonephritis associated with hepatitis C infection, bacterial endocarditis, and shunt nephritis
C. MESANGIAL IMMUNE DEPOSITS
1. IgA nephropathy, Schönlein-Henoch purpura
D. ANTI-GBM DISEASE
1. Diffuse linear deposition of Ig
Immunologic Mechanisms Not Clearly Established
1. Minimal change nephropathy
2. Focal glomerulosclerosis
3. Hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura
4. ANCA-associated disease: Wegener’s granulomatosis and small-vessel vasculitis
5. Type II MPGN (dense deposit disease)
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