A 42-year-old man comes to the office for evaluation of progressive generalized edema and weight gain for the past several weeks. He has no chest pain or shortness of breath. The patient has no chronic medical conditions and takes no medications. He last saw a physician a year ago for an upper respiratory infection. The patient does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/80 mm Hg and pulse is 84/min. Mild ascites is present. There is bilateral lower extremity pitting edema to the knees.Laboratory results are as follows: Urinary protein excretion is 6.0 g/24 hr. A kidney biopsy is performed, and electron microscopy of a glomerular capillary is shown below: Which of the following is the most likely diagnosis?

Question

A 42-year-old man comes to the office for evaluation of progressive generalized edema and weight gain for the past several weeks.  He has no chest pain or shortness of breath.  The patient has no chronic medical conditions and takes no medications.  He last saw a physician a year ago for an upper respiratory infection.  The patient does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 130/80 mm Hg and pulse is 84/min.  Mild ascites is present.  There is bilateral lower extremity pitting edema to the knees.Laboratory results are as follows:  Urinary protein excretion is 6.0 g/24 hr.  A kidney biopsy is performed, and electron microscopy of a glomerular capillary is shown below:  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_3a3e_5f3b_9249_219e4ed2c711_MD0001_00 This patient has nephrotic syndrome, characterized by generalized edema, heavy proteinuria (>3.5 g/day), and hypoalbuminemia. Electron microscopy (EM) of the glomerular capillary demonstrates irregular, electron-dense immune deposits located on the glomerular basement membrane (GBM) with moderate effacement of the podocyte foot processes, consistent with membranous nephropathy (MN). MN results from immune-complex deposition in the subepithelial portions of the GBM. Light microscopy demonstrates diffuse glomerular capillary wall thickening without hypercellularity, whereas silver staining reveals "spikes and domes" of GBM that protrude between the immune deposits (which do not stain). Immunofluorescence microscopy demonstrates a diffuse granular pattern of IgG and C3 along the capillary loops. MN is one of the most common causes of nephrotic syndrome in adults. Primary (idiopathic) MN is thought to be caused by autoantibodies directed at the phospholipase A2 receptor, whereas secondary MN can be associated with a variety of conditions including systemic lupus erythematosus, viral hepatitis, and solid tumors. (Choices A and E) Crescentic glomerulonephritis (GN) and poststreptococcal GN are nephritic diseases that are characterized by hematuria, red blood cell casts, and hypertension (not heavy proteinuria). Poststreptococcal GN typically occurs in children two to four weeks after a group A streptococcal infection, and EM demonstrates large, subepithelial immune-complex "humps." Crescentic (rapidly progressive) GN can occur in a number of diseases (eg, anti-GBM disease, antineutrophil cytoplasmic antibody vasculitis); proliferative crescents are visible on light microscopy, and EM may demonstrate rupture of the GBM. (Choice B) Focal segmental glomerulosclerosis also causes nephrotic syndrome but is characterized by sclerosis and hyalinosis of portions of some, but not all, glomeruli. EM demonstrates diffuse foot process effacement; however, immune deposits (if present) typically occur in the sclerotic region of the glomerulus, not along the GBM. (Choice D) Minimal change disease causes nephrotic syndrome but occurs more commonly in children. EM demonstrates extensive, diffuse effacement of the foot processes, and immune complexes are not seen. Educational objective: Membranous nephropathy is a common cause of nephrotic syndrome in adults. Electron microscopy of the glomerular capillary demonstrates irregular, subepithelial, electron-dense immune deposits on the glomerular basement membrane with moderate effacement of the podocyte foot processes; immunofluorescence microscopy demonstrates a diffuse granular pattern of IgG along the capillary loops.

A 42-Year-Old Man Comes to the Office for Evaluation of Progressive