Acute glomerulonephritis is a relatively uncommon cause of AKI, accounting for about 5% of cases. Pathologically, inflammatory glomerular lesions are seen. These include mesangioproliferative, focal and diffuse proliferative, and crescentic lesions. The larger the percentage of glomeruli involved and the more severe the lesion, the more likely it is that the patient will have a poor clinical outcome.
Glomerulonephritides are classified into one of five pathophysiologic processes, which can be aided by serologic analysis. Markers include anti-GBM antibodies, antineutrophil cytoplasmic antibodies (ANCAs), and other immune markers of disease.
Immune complex deposition occurs when there is moderate overproduction of antigen compared to antibody production. Complexes formed with marked antigen excess tend to remain in the circulation. Antibody excess with large antigen–antibody aggregates usually results in phagocytosis and clearance of the precipitates by the mononuclear phagocytic system in the liver and spleen. Causes include 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 termed “Goodpasture syndrome (eFigure 22–5).” Injury is related to autoantibodies against type IV collagen in the GBM rather than to immune complex deposition (eFigure 22–6).
Anti-GBM crescent. (Used, with permission, from Jean Olson, MD.)
Anti-GBM. (Immunofluorescence stain.) (Used, with permission, from Jean Olson, MD.)
Pauci-immune acute glomerulonephritis is a form of small-vessel vasculitis associated with ANCAs, causing kidney diseases 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 of disease. Cytoplasmic ANCA (c-ANCA) is the common pattern. Microscopic polyangiitis is another pauci-immune vasculitis causing acute glomerulonephritis, which is more commonly associated with perinuclear staining (p-ANCA). ANCA-associated and anti-GBM–associated acute glomerulonephritides can evolve to crescentic glomerulonephritis and often have poor outcomes unless treatment is started early.
Monoclonal immunoglobulin–mediated glomerulonephritis is characterized by the deposition of a monoclonal immunoglobulin in glomeruli or tubular basement membrane or both. It is detected on immunofluorescent or immunohistochemical staining of kidney biopsies as monotypic immunoglobulin deposits. Serum protein electrophoresis and serum free light chains are useful diagnostic tests to perform when monoclonal immunoglobulin–mediated glomerulonephritis is suspected or confirmed. While many cases will occur in the setting of a monoclonal gammopathy, this is not always the case.
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. While checking the serum C3 level may be helpful, normal levels do not rule out C3 glomerulopathy.
Other vascular causes of glomerulonephritis include hypertensive emergencies and the thrombotic microangiopathies such as hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura (see Chapter 14).