GLOMERULONEPHRITIS

Essentials of Diagnosis

Hematuria, dysmorphic red cells, red cell casts, and mild proteinuria.

Dependent edema and hypertension.

Acute renal insufficiency.

General Considerations
Acute glomerulonephritis is a relatively uncommon cause of acute renal failure, accounting for about 5% of cases of intrinsic renal failure. 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.
Categorization of acute glomerulonephritis can be done by serologic analysis. Markers include antineutrophil cytoplasmic antibodies (ANCA), anti-GBM antibodies, and other immune markers of disease.
Immune complex deposition usually occurs when moderate antigen excess over antibody production occurs. 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 (Berger’s disease), peri-infectious or postinfectious glomerulonephritis, endocarditis, lupus nephritis, cryoglobulinemic glomerulonephritis (often associated with hepatitis C virus), and membranoproliferative glomerulonephritis.
Anti-GBM–associated acute glomerulonephritis is either confined to the kidney or associated with pulmonary hemorrhage. The latter is termed "Goodpasture’s syndrome" (see micrograph). Injury is related to autoantibodies aimed against type IV collagen in the GBM rather than to immune complex deposition (see micrograph).

Pauci-immune acute glomerulonephritis is a form of small-vessel vasculitis associated with ANCA, causing primary and secondary renal diseases that do not have direct immune complex deposition or antibody binding (see micrograph). Tissue injury is believed to be due to cell-mediated immune processes. An example is Wegener’s granulomatosis, 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 a common pattern. Microscopic polyangiitis is another pauci-immune vasculitis causing acute glomerulonephritis. Perinuclear staining (P-ANCA) is the common pattern. ANCA-associated and anti-GBM-associated acute glomerulonephritis can evolve to crescentic glomerulonephritis and often have poor outcomes unless treatment is started early. Both are described more fully below.
Other vascular causes of acute glomerulonephritis include malignant hypertension and the thrombotic microangiopathies such as hemolytic-uremic syndrome (see Hypertension) and thrombotic thrombocytopenic purpura (see Hematology).
Clinical Findings
SYMPTOMS AND SIGNS
Patients with acute glomerulonephritis are often hypertensive and edematous, and have an abnormal urinary sediment. The edema is found first in body parts with low tissue tension, such as the periorbital and scrotal regions.
LABORATORY FINDINGS
Dipstick and microscopic evaluation will reveal evidence of hematuria, moderate proteinuria (usually < 2 g/d), and cellular elements such as red cells, red cell casts, and white cells. Red cell casts are specific for glomerulonephritis, and a detailed search is warranted. Twenty-four hour urine for protein excretion and creatinine clearance quantifies the amount of proteinuria and documents the degree of renal dysfunction. However, in cases of rapidly changing serum creatinine values, the urinary creatinine clearance is an unreliable marker of GFR. The FENa is usually low unless renal dysfunction is marked.
Further tests include complement levels (C3, C4, CH50), ASO titer, anti-GBM antibody levels, ANCAs, antinuclear antibody titers, cryoglobulins, hepatitis serologies, blood cultures, renal ultrasound, and occasionally renal biopsy.
Treatment
Depending on the nature and severity of disease, treatment can consist of high-dose corticosteroids and cytotoxic agents such as cyclophosphamide. Plasma exchange can be used in Goodpasture’s disease as a temporizing measure until chemotherapy can take effect. Treatment and prognosis for specific diseases are discussed more fully below.

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