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Review Question - QID 101019

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QID 101019 (Type "101019" in App Search)
A 60-year-old man with a history of osteoarthritis has been awaiting hip replacement surgery for 3 years. During his annual physical, he reports that he has been taking over the counter pain medications, but that no amount of analgesics can relieve his constant pain. Laboratory results reveal that his renal function has deteriorated when compared to his last office visit 2 years ago. Serum creatinine is 2.0 mg/dL, and urinalysis shows 1+ proteinuria. There are no abnormalities seen on microscopy of the urine. A renal biopsy shows eosinophilic infiltration and diffuse parenchymal inflammation. What is the most likely explanation for this patient's deterioration in renal function?

Focal segmental glomerulosclerosis

6%

14/248

Ischemic acute tubular necrosis

4%

11/248

Nephrotoxic acute tubular necrosis

16%

39/248

Toxic tubulointerstitial nephritis

65%

161/248

Rapidly progressive glomerulonephritis

6%

16/248

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The question stem describes a patient who is overusing analgesics. In this scenario, the most likely explanation for deterioration in renal function is NSAID-induced toxic tubulointerstitial nephritis (TIN).

As a mechanism of renal injury, NSAIDs decrease prostaglandin synthesis, resulting in ischemic damage to the kidney by decreasing afferent arteriole dilation that is mediated by prostaglandins. Additionally, NSAIDs uncouple oxidative phosphorylation in renal mitochondria, causing direct oxidative damage.

Bakris et al. report that as a result of widespread availability and misuse, NSAIDs have become a common cause of acute renal failure. The clinical presentation of NSAID-associated TIN differs from that of antibiotic-associated TIN in that proteinuria is much more common with NSAID-associated TIN, while eosinophilia, eosinophiluria, fever and rash are more common with antibiotic-associated TIN.

As reviewed by John et al., drugs can be a common cause of renal disease. Drug induced renal injuries classically present as TIN, acute tubular necrosis (ATN), and glomerular or vascular disease. Drug-induced TIN and ATN are much more common than drug-induced glomerular and vascular disease, which are rare.

Illustration A demonstrates the classic findings of TIN on renal biopsy. Note the diffuse damage, as well as the eosinophils in the right upper center of the image.

Incorrect Answers:
Answer 1: FSGS classically presents with focal and segmental glomerulosclerosis, not as diffuse inflammation with eosinophils.

Answer 2: Ischemic ATN would present with muddy-brown/granular casts on urine microscopy, as a result of reduced blood flow to the kidneys (e.g. sepsis).

Answer 3: Nephrotoxic ATN would present with muddy-brown/granular casts on urine microscopy, as a result of classically aminoglycosides or radiocontrast dyes.

Answer 5: RPGN classically presents with crescent-shaped glomeruli on biopsy.

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