22-09: Glomerulonephritis

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Acute glomerulonephritis is an uncommon cause of AKI, accounting for about 5% of cases. Pathologically, inflammatory glomerular lesions are seen. These include mesangioproliferative, focal and diffuse endocapillary proliferative, and crescentic lesions. The larger the percentage of glomeruli involved and the more severe the lesion, the higher the risk of a poor clinical outcome.

Glomerulonephritides are classified into five pathophysiologic processes, which are characterized by serologic analysis. Markers include anti-GBM antibodies, antineutrophil cytoplasmic antibodies (ANCAs), and other immune markers of disease.

Immune complex glomerulonephritis occurs when autoantibodies develop and combine with antigens to form immune complexes that deposit within glomeruli. There are several distinct immune complex glomerulonephritides, including IgA nephropathy, infection-related glomerulonephritis, lupus nephritis, and cryoglobulinemic glomerulonephritis (often associated with hepatitis C virus [HCV]).

Anti-GBM–associated acute glomerulonephritis is either confined to the kidney or associated with pulmonary hemorrhage. The latter is called “Goodpasture syndrome” (eFigure 22–5). Injury is related to autoantibodies against type IV collagen in the GBM (eFigure 22–6).

Pauci-immune acute glomerulonephritis is a form of small-vessel vasculitis associated with ANCAs, causing kidney disease without direct immune complex deposition or antibody binding (see eFigure 22–3). Tissue injury is believed to be due to cell-mediated immune processes. An example is granulomatosis with polyangiitis, a systemic necrotizing vasculitis of small arteries and veins associated with intravascular and extravascular granuloma formation. In addition to glomerulonephritis, these patients can have upper airway, pulmonary, and skin manifestations. Cytoplasmic ANCA (c-ANCA) is the common staining pattern. Microscopic polyangiitis is another pauci-immune vasculitis causing glomerulonephritis, and is more commonly associated with perinuclear staining (p-ANCA).

ANCA-associated and anti-GBM–associated acute glomerulonephritides have poor outcomes unless treatment is started early.

Monoclonal immunoglobulin–mediated glomerulonephritis is characterized by the deposition of a monoclonal immunoglobulin in glomeruli, the tubular basement membrane, or both. Immunofluorescent or immunohistochemical staining of kidney biopsies detects monotypic immunoglobulin deposits. Many cases occur in the setting of an identifiable monoclonal gammopathy, but this is not always the case. Serum protein electrophoresis, immunofixation, and free light chain analysis are important diagnostic tests to perform when monoclonal immunoglobulin–mediated glomerulonephritis is suspected or confirmed.

C3 glomerulopathy results from predominant C3 deposition in the glomeruli with or without minimal deposition of immunoglobulins. It is also identified by immunofluorescence or immunohistochemistry. The pathogenesis of C3 glomerulonephropathy stems from abnormalities in regulation of the alternative pathway of complement. Measurement ...