A 5-year-old boy is brought to the office with generalized edema that developed following a mild upper respiratory infection. Medical history is unremarkable. Blood pressure and heart rate are normal. Serum creatinine levels are normal. Urinalysis shows massive proteinuria with no hematuria. Further analysis reveals that urine protein consists principally of albumin with only trace amounts of IgG and alpha-2-macroglobulin. Which of the following pathologic changes is the most likely cause of this patient's urinary protein loss?

Question

A 5-year-old boy is brought to the office with generalized edema that developed following a mild upper respiratory infection.  Medical history is unremarkable.  Blood pressure and heart rate are normal.  Serum creatinine levels are normal.  Urinalysis shows massive proteinuria with no hematuria.  Further analysis reveals that urine protein consists principally of albumin with only trace amounts of IgG and alpha-2-macroglobulin.  Which of the following pathologic changes is the most likely cause of this patient's urinary protein loss?

Quizplus · Accepted Answer

11ec160b_3a37_a86e_9249_f390328a2b58_MD0001_00 This pediatric patient presenting with generalized edema and massive proteinuria following an upper respiratory infection likely has minimal change disease, the most common cause of nephrotic syndrome in children. Minimal change disease is caused by immune dysregulation, as suggested by its association with respiratory infections, immunizations, and atopic disorders, as well as its excellent response to corticosteroids. Immune dysfunction leads to overproduction of a glomerular permeability factor (possibly IL-13) that directly damages podocytes, leading to foot process effacement and fusion as well as decreased anionic properties of the glomerular basement membrane. Loss of negative charge leads to selective loss of albumin in the urine (selective albuminuria), in contrast to the nonselective proteinuria seen with other forms of nephrotic syndrome (eg, membranous nephropathy, focal segmental glomerulosclerosis). Despite the dramatic clinical picture, light microscopy and immunofluorescence studies show completely normal kidneys; the characteristic effacement of the podocyte foot processes can be detected only by electron microscopy. (Choice A) Crescent formation is a sign of severe glomerular injury; it is associated with rapidly progressive glomerulonephritis (RPGN), which can occur secondary to multiple diseases (eg, anti-glomerular basement membrane disorder, antineutrophil cytoplasmic antibody vasculitides). However, RPGN typically presents with renal insufficiency and nephritic urine sediment (ie, hematuria, red blood cell casts); massive proteinuria would be unexpected. (Choice C) Nodular glomerulosclerosis (Kimmelstiel-Wilson lesions) occurs in patients with diabetic nephropathy and is characterized by ovoid nodules of hyaline material within the mesangium. Although diabetic nephropathy may present as nephrotic syndrome, patients are typically middle-aged to elderly with a long history of diabetes mellitus. (Choice D) Thinning of the glomerular basement membrane is seen in thin basement membrane nephropathy and Alport syndrome. Thin basement membrane nephropathy is a benign condition typically associated with microscopic hematuria. Alport syndrome is caused by an inherited defect in the formation of type IV collagen; patients have hearing loss, ocular abnormalities, hematuria, and progressive renal insufficiency. (Choice E) Focal tubular epithelial necrosis and cell shedding occur in acute tubular necrosis, which typically follows renal ischemia or exposure to nephrotoxins (eg, aminoglycosides). It manifests as acute renal injury with muddy brown casts, not nephrotic syndrome. Educational objective: Minimal change disease is caused by immune dysregulation and overproduction of a glomerular permeability factor, which damages podocytes and decreases the anionic properties of the glomerular basement membrane. This results in selective loss of albumin in the urine, in contrast to the nonselective proteinuria seen in other forms of nephrotic syndrome.

A 5-Year-Old Boy Is Brought to the Office with Generalized