A 32-year-old man with a history of chronic hepatitis B infection is evaluated for generalized edema. Kidney disease is suspected, and renal biopsy is performed. Histologic sections of the kidney show diffuse glomerular hypercellularity and diffuse thickening of the capillary walls. Immunofluorescence demonstrates prominent staining for IgG and C3 with coarse, granular basement membrane and mesangial positivity. Electron microscopy shows extensive subendothelial and mesangial deposits. Which of the following is the most likely diagnosis?
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This patient's kidney biopsy findings are consistent with membranoproliferative glomerulonephritis (MPGN). The most common type, MPGN type I, is caused by glomerular immune complex deposition in the capillary walls and mesangium. The antigen-antibody complexes typically arise from chronic infection (eg, hepatitis B virus, hepatitis C virus), autoimmune disease (eg, systemic lupus erythematosus), or malignancy (eg, chronic lymphocytic leukemia). In some cases, however, the underlying etiology is unknown (ie, primary MPGN).
These immune complexes activate complement pathways, resulting in inflammatory glomerular damage that can cause symptoms of nephrotic (eg, proteinuria, edema) and nephritic syndrome (eg, hematuria).
Microscopic examination shows a characteristic pattern of glomerular injury:
Light microscopy (LM) shows large, lobular glomeruli that are hypercellular due to the proliferation of mesangial cells, endothelial cells, and leukocytes. Immune complex deposition results in thickened capillary walls, as well as the synthesis of new basement membrane material, which imparts a split (ie, tram track) appearance seen with special stains.
Immunofluorescence demonstrates a granular pattern of IgG and C3 deposition within the capillary walls and mesangium.
Electron microscopy (EM) shows subendothelial (ie, between the glomerular basement membrane and endothelium) and mesangial deposits.
(Choice A) Amyloidosis commonly involves the kidney and can cause nephrotic syndrome. However, LM demonstrates amorphous, eosinophilic glomerular deposits (composed of misfolded proteins) that show apple-green birefringence under polarized light when stained with Congo red.
(Choice B) Focal segmental glomerulosclerosis also causes nephrotic syndrome, but LM shows sclerosis that affects portions of some glomeruli. It is more often associated with HIV infection than hepatitis B infection.
(Choice D) Membranous nephropathy is a common cause of nephrotic syndrome that may be associated with hepatitis B infection. However, LM shows diffuse thickening of the glomerular capillary walls without significant hypercellularity. EM demonstrates subepithelial (not subendothelial) deposits.
(Choice E) Polyarteritis nodosa is a systemic vasculitis that often affects medium-sized arteries in the kidney. It is associated with chronic hepatitis B infection, but LM shows transmural arterial inflammation with fibrinoid necrosis (eg, fibrin deposition in the vessel wall).
Educational objective:
Membranoproliferative glomerulonephritis is typically caused by immune complex deposition within the glomerular capillary walls and mesangium and can be associated with chronic infections (eg, hepatitis B). It is characterized by large, hypercellular glomeruli with thickened capillary walls. Immunofluorescence typically shows a granular pattern of IgG and C3. Electron microscopy shows subendothelial and mesangial deposits.