A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 48-year-old woman with chronic tension headaches comes to the physician because of several episodes of bilateral flank pain and reddish urine within the past month. Current medications include aspirin, which she takes almost daily for headaches. Her temperature is 37.4°C (99.3°F) and her blood pressure is 150/90 mm Hg. Physical examination shows costovertebral tenderness to percussion bilaterally. Laboratory studies show a hemoglobin concentration of 10.2 g/dL and serum creatinine concentration of 2.4 mg/dL. Urine studies show:
Urine
Protein
3+
RBC > 16/hpf
WBC 2/hpf
There are no casts or dysmorphic RBCs visualized on microscopic analysis of the urine. Which of the following is the most likely underlying cause of this patient's hematuria?"
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A
Tubular lumen obstruction by protein castsIncorrect. Tubular protein casts (Bence-Jones proteinuria) cause cast nephropathy in multiple myeloma; this patient's history of chronic aspirin use and lack of paraproteinemia clues point elsewhere.
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B
Necrotizing inflammation of the renal glomeruliIncorrect. Necrotizing glomerulonephritis would show dysmorphic RBCs and RBC casts on urinalysis, which are explicitly absent here.
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C
Bacterial infection of the renal parenchymaIncorrect. Bacterial pyelonephritis causes WBC casts and dysuria with positive cultures, not isolated hematuria with proteinuria in a chronic NSAID user.
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D
Vasoconstriction of the medullary vesselsCorrect. Chronic NSAID/aspirin use inhibits prostaglandin-mediated vasodilation of the vasa recta, causing medullary ischemia and papillary necrosis with hematuria.
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E
Immune complex deposition in glomerular basement membraneIncorrect. Immune complex deposition produces glomerulonephritis with dysmorphic RBCs and RBC casts, which are explicitly absent on this urinalysis; chronic analgesic use causes papillary necrosis through medullary vasoconstriction.
↑ Tap an answer to reveal the reasoning
Answer: D. This patient with chronic daily aspirin use, hypertension, mild renal insufficiency, and now hematuria with flank pain has analgesic nephropathy (chronic interstitial nephritis with renal papillary necrosis). Long-term use of NSAIDs/aspirin (especially in combination with phenacetin historically) causes medullary ischemia by inhibiting prostaglandin-mediated vasodilation of the vasa recta, the medullary blood supply.
Prostaglandins (PGE2, PGI2) normally counteract vasoconstrictive forces in the medulla; NSAID inhibition of COX removes this protective vasodilation, producing chronic medullary ischemia and papillary necrosis. Sloughed papillae can shed into the urinary tract, producing painless hematuria, flank pain (if a papilla causes obstruction), and sterile pyuria. Imaging shows classic 'ring' or 'shrunken papilla' signs.
Key distinguishers: protein-cast obstruction (multiple myeloma cast nephropathy with Bence-Jones proteinuria); necrotizing glomerulonephritis (red cell casts, dysmorphic RBCs, ANCA disease); pyelonephritis (WBC casts, dysuria, fever); medullary vasoconstriction from NSAID use (papillary necrosis) - the picture here. Risk factors for papillary necrosis: NSAIDs, sickle cell disease, diabetes, urinary tract obstruction (mnemonic: SAAD POP - Sickle cell, Acute pyelonephritis, Analgesic abuse, Diabetes).
**Why each option:**
**A.** Tubular protein casts (Bence-Jones proteinuria) cause cast nephropathy in multiple myeloma; this patient's history of chronic aspirin use and lack of paraproteinemia clues point elsewhere.
**B.** Necrotizing glomerulonephritis would show dysmorphic RBCs and RBC casts on urinalysis, which are explicitly absent here.
**C.** Bacterial pyelonephritis causes WBC casts and dysuria with positive cultures, not isolated hematuria with proteinuria in a chronic NSAID user.
**D.** Correct. Chronic NSAID/aspirin use inhibits prostaglandin-mediated vasodilation of the vasa recta, causing medullary ischemia and papillary necrosis with hematuria.