A 60-year-old woman is being evaluated for abnormal renal function. She is found to have a serum creatinine of 2.2 mg/dL on routine laboratory monitoring; her creatinine level a year ago was 1.2 mg/dL. The patient has a history of nonischemic cardiomyopathy and systolic heart failure and has been on a stable medical regimen for the past 2 years. She has no dyspnea, fever, rash, or lower extremity swelling but has been taking ibuprofen for 2 weeks due to left knee osteoarthritis. Urinalysis reveals the following:
| Protein | none |
| White blood cells | none |
| Red blood cells | none |
| Sediment | none |
Ibuprofen is discontinued, and her kidney function returns to normal in a week. Which of the following best explains this patient's transient deterioration in renal function?
Show Explanatory Sources
This patient developed acute kidney injury after taking ibuprofen. Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen, aspirin, naproxen) exert their anti-inflammatory, analgesic, and antipyretic effects through the inhibition of the cyclooxygenase enzymes. These enzymes are the rate-limiting step in the formation of prostanoids (ie, prostaglandins, thromboxane), which are involved in mediating pain and inflammation.
Prostaglandins also help maintain renal perfusion by dilating the afferent arteriole, particularly in patients with intravascular volume depletion (eg, congestive heart failure, diarrhea, excessive diuresis) or chronic kidney disease. In such patients, increased prostaglandin synthesis is necessary to preserve renal blood flow and maintain glomerular filtration rate. In at-risk patients, inhibition of afferent dilation with NSAIDs results in reduced glomerular filtration and prerenal azotemia with elevations in creatinine and blood urea nitrogen (ratio >20:1).
NSAID-induced acute kidney injury is often diagnosed incidentally on laboratory tests performed for other reasons, and patients are generally asymptomatic. Urinalysis is typically bland without proteinuria, hematuria, or casts. Prolonged NSAID use can cause chronic kidney disease (analgesic nephropathy) due to papillary necrosis and chronic interstitial nephritis.
(Choice B) Activation of the renin-angiotensin-aldosterone system results in efferent arteriole constriction, and ACE inhibitors (eg, lisinopril) cause efferent vasodilation. These medications can cause acute kidney injury, particularly in patients with volume depletion or bilateral renal artery stenosis. However, NSAID-induced kidney injury is due to impaired afferent arteriole vasodilation.
(Choice C) NSAIDs are a common cause of acute interstitial nephritis (AIN). However, urinalysis in AIN typically demonstrates white blood cells and white blood cell casts, and patients commonly develop fevers and rash.
(Choice D) Acute tubular necrosis (ATN) can occur due to toxic (eg, aminoglycosides, radiocontrast agents) or ischemic (eg, hypotension) insults. However, urinalysis would demonstrate muddy-brown, granular casts, and NSAIDs are not commonly associated with ATN.
(Choice E) Vasculitis involving the glomerular capillaries (eg, granulomatosis with polyangiitis, microscopic polyangiitis) causes a nephritic syndrome; urinalysis would demonstrate red blood cells and red blood cell casts. In addition, patients with vasculitides typically have associated systemic symptoms (eg, fever, fatigue, weight loss).
Educational objective:
Patients with intravascular volume depletion (eg, congestive heart failure, diarrhea, excessive diuresis) and chronic kidney disease depend on renal prostaglandin production to dilate the afferent glomerular arteriole and maintain the glomerular filtration rate. Nonsteroidal anti-inflammatory drugs inhibit prostaglandin synthesis, which can cause prerenal azotemia in at-risk patients.