A 42-year-old man comes to the office due to hematuria, fatigue, and nasal congestion for the last few weeks. He has no chronic medical conditions. Blood pressure is 160/96 mm Hg. Physical examination shows edema around the ankles, hands, and face. Laboratory results reveal blood urea nitrogen of 40 mg/dL and serum creatinine of 3.8 mg/dL. Urinalysis shows moderate proteinuria and a large amount of red blood cells (RBCs) with RBC casts. A kidney biopsy is performed. Light microscopy reveals cellular proliferation, focal necrosis, and crescent formation of most of the glomeruli. On immunofluorescent microscopy, there are no immunoglobulin or complement deposits. Which of the following additional findings is most likely to be present in this patient?

Question

A 42-year-old man comes to the office due to hematuria, fatigue, and nasal congestion for the last few weeks.  He has no chronic medical conditions.  Blood pressure is 160/96 mm Hg.  Physical examination shows edema around the ankles, hands, and face.  Laboratory results reveal blood urea nitrogen of 40 mg/dL and serum creatinine of 3.8 mg/dL.  Urinalysis shows moderate proteinuria and a large amount of red blood cells (RBCs) with RBC casts.  A kidney biopsy is performed.  Light microscopy reveals cellular proliferation, focal necrosis, and crescent formation of most of the glomeruli.  On immunofluorescent microscopy, there are no immunoglobulin or complement deposits.  Which of the following additional findings is most likely to be present in this patient?

Quizplus · Accepted Answer

Crescent formation on light microscopy is diagnostic of rapidly progressive (crescentic) glomerulonephritis (RPGN). This is a syndrome of severe glomerular injury that rapidly progresses to renal failure within weeks to months of onset. RPGN can be caused by several different diseases and is classified based on immunologic findings: Antiglomerular basement membrane (anti-GBM) RPGN: Linear GBM deposits of IgG and C3 are found on immunofluorescence (Choice C). In some patients, anti-GBM antibodies cross-react with pulmonary alveolar basement membranes, producing pulmonary hemorrhages (Goodpasture syndrome). Immune-complex RPGN: There is a "lumpy-bumpy" granular pattern of staining for both antibodies (eg, IgG, IgA) and complement on immunofluorescence microscopy. This can be a complication of poststreptococcal glomerulonephritis, systemic lupus erythematosus, IgA nephropathy, or Henoch-Schönlein purpura. Pauci-immune RPGN: There are no immunoglobulin or complement deposits on the basement membrane, as with this patient. Most patients have elevated serum titers of antineutrophil cytoplasmic antibodies (ANCA). This condition is often associated with vasculitides (eg, granulomatosis with polyangiitis, microscopic polyangiitis) but can also be idiopathic. (Choices A and B) Serum C3 and C4 levels are usually normal with pauci-immune RPGN. Decreased serum C3 or C4 levels often occur in diseases with prominent immune complex formation, such as poststreptococcal glomerulonephritis, systemic lupus erythematosus (which causes immune-complex RPGN), and membranoproliferative glomerulonephritis. (Choice E) Serum antiphospholipid antibodies are detected in patients with autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome. Antiphospholipid antibodies are associated with venous and arterial thrombosis, not crescent formation. Educational objective: Pauci-immune rapidly progressive glomerulonephritis frequently occurs as a manifestation of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (eg, granulomatosis with polyangiitis, microscopic polyangiitis). It is characterized by glomerular crescent formation without immunoglobulin or complement deposits.

A 42-Year-Old Man Comes to the Office Due to Hematuria