A 34-year-old man is being evaluated for acute hematuria and oliguria. He has no chronic medical conditions and takes no medications on a regular basis. Blood pressure is 170/100 mm Hg. Blood urea nitrogen is 38 mg/dL and serum creatinine is 4.5 mg/dL. The patient undergoes a kidney biopsy and the following microscopic changes are seen after silver staining to highlight the glomerular tuft: The area marked with an arrow is likely to have abnormal deposition of which of the following substances?

Question

A 34-year-old man is being evaluated for acute hematuria and oliguria.  He has no chronic medical conditions and takes no medications on a regular basis.  Blood pressure is 170/100 mm Hg.  Blood urea nitrogen is 38 mg/dL and serum creatinine is 4.5 mg/dL.  The patient undergoes a kidney biopsy and the following microscopic changes are seen after silver staining to highlight the glomerular tuft:  The area marked with an arrow is likely to have abnormal deposition of which of the following substances?

Quizplus · Accepted Answer

This patient with acute renal failure and hematuria has a glomerular crescent, defined as >2 layers of proliferating cells within Bowman's space. Glomerular crescent formation occurs in response to immune or inflammatory-mediated injury to glomerular capillaries. Disruption of the glomerular basement membrane allows gaps to form within the capillary, resulting in an influx of coagulation factors (eg, fibrinogen) and inflammatory cells (eg, lymphocytes, macrophages) into Bowman's space. Initiation of the coagulation cascade promotes the deposition of large quantities of fibrin, while inflammatory cells proliferate and release growth factors and inflammatory cytokines that recruit fibroblasts and stimulate parietal cell proliferation. This eventually results in progressive glomerular hypercellularity, fibrosis, and irreversible renal injury. Crescent formation is diagnostic of rapidly progressive glomerulonephritis (RPGN), a syndrome of severe renal injury that can occur in a number of disease processes (eg, anti-glomerular basement antibody [Goodpasture] disease, granulomatosis with polyangiitis). Like other nephritic syndromes, it typically presents with hematuria, hypertension, and progressive renal failure; however, renal decompensation and progression to end-stage renal disease occur particularly quickly (weeks to months) in RPGN. (Choice A) Amyloid is visualized as amorphous deposits on light microscopy or, when stained with Congo red, as apple-green, birefringent deposits under polarized light. It is associated with nephrotic syndrome (heavy proteinuria, hyperlipidemia), not with nephritic syndrome as seen in this patient. (Choice C) Goodpasture disease can cause RPGN and is characterized by antibodies against the glomerular basement membrane. However, these antibodies are usually IgG, or occasionally IgM or IgA. In contrast, IgE antibodies mediate immediate hypersensitivity reactions and are involved in defense against certain parasites. (Choice D) The clear cells seen in renal cell carcinoma (RCC) have a high lipid content, which is responsible for the yellow tinge noted on gross examination. RCC can cause hematuria and hypertension but does not cause crescent formation or renal failure. (Choice E) Myoglobinuria is seen in rhabdomyolysis; urine dipstick is positive for blood, but red blood cells are absent on urinalysis. Myoglobin is toxic to renal tubular cells and induces acute tubular necrosis, not glomerular injury and crescent formation. Educational objective: Crescent formation on light microscopy is diagnostic for rapidly progressive glomerulonephritis. Crescents consist of glomerular parietal cells, lymphocytes, and macrophages along with abundant fibrin deposition. Crescents eventually become fibrotic, disrupting glomerular function and causing irreversible renal injury.

A 34-Year-Old Man Is Being Evaluated for Acute Hematuria and Oliguria