A 40-year-old man comes to the physician because of a two-week history of fatigue, lower extremity edema, and dark urine. He has no history of serious illnesses. He takes no medications. He does not use tobacco, alcohol, or drugs. His blood pressure is 132/83 mm Hg and pulse is 84/min. Physical examination shows symmetric pitting edema of lower extremities. Laboratory studies show a serum creatinine level of 1.1 mg/dL. Urinalysis shows 4+ proteinuria and microhematuria. Electron microscopy of the specimen obtained from kidney biopsy shows dense deposits within glomerular basement membrane. Immunofluorescence microscopy is positive for C3, not immunoglobulins. Which of the following is the most likely pathophysiologic mechanism that explains this patient's condition?

Question

A 40-year-old man comes to the physician because of a two-week history of fatigue, lower extremity edema, and dark urine.  He has no history of serious illnesses.  He takes no medications.  He does not use tobacco, alcohol, or drugs.  His blood pressure is 132/83 mm Hg and pulse is 84/min.  Physical examination shows symmetric pitting edema of lower extremities.  Laboratory studies show a serum creatinine level of 1.1 mg/dL.  Urinalysis shows 4+ proteinuria and microhematuria.  Electron microscopy of the specimen obtained from kidney biopsy shows dense deposits within glomerular basement membrane.  Immunofluorescence microscopy is positive for C3, not immunoglobulins.  Which of the following is the most likely pathophysiologic mechanism that explains this patient's condition?

Quizplus · Accepted Answer

This patient with nephrotic-range proteinuria and hematuria most likely has membranoproliferative glomerulonephritis. Dense intramembranous deposits that stain for C3 is a characteristic microscopic finding for membranoproliferative glomerulonephritis, type 2 (also called dense deposit disease). This condition is unique among glomerulopathies, because it is caused by IgG antibodies (termed C3 nephritic factor) directed against C3 convertase of the alternative complement pathway. These antibodies reacting with C3 convertase lead to persistent complement activation and kidney damage. (Choice A) Anti-GBM antibodies are characteristic for Goodpasture's syndrome. (Choice B) Circulating immune complexes account for the group of glomerulonephritis called immune complex-mediated glomerulopathies that include SLE, post-streptococcal glomerulonephritis, etc. (Choice D) Cell-mediated injury may be important in idiopathic crescentic glomerulonephritis. (Choice E) Non-immunologic kidney damage is believed to operate in diabetic nephropathy, hypertensive nephropathy, etc. Educational objective: Membranoproliferative glomerulonephritis, type 2, is a unique glomerulopathy that is caused by persistent activation of the alternative complement pathway.

A 40-Year-Old Man Comes to the Physician Because of a Two-Week