Which medication should be discontinued in a patient with impaired renal function, taking losartan (angiotensin II receptor antagonist) and amlodipine (calcium channel blocker) for hypertension, omeprazole (proton pump inhibitor) for gastroesophageal reflux disease, naproxen (nonsteroidal anti-inflammatory drug) for knee osteoarthritis, and atorvastatin (HMG-CoA reductase inhibitor) for hyperlipidemia, presenting with pyuria and leukocyturia?

From the Guidelines

The correct option is D, Naproxen and atorvastatin, however considering the provided evidence and the clinical context, the most appropriate choice would be to discontinue Naproxen. The patient is experiencing acute kidney injury (AKI) as evidenced by the significant rise in serum creatinine from 0.9 mg/dL to 2.6 mg/dL over three months. The urinalysis findings showing leukocytes, leukocyte casts, and granular casts suggest acute interstitial nephritis (AIN), which is commonly caused by medications.

• Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is known to cause AIN and can directly impair kidney function by reducing prostaglandin-mediated vasodilation of the afferent arteriole, decreasing renal blood flow 1.
• The use of NSAIDs, including naproxen, is recommended to be avoided in patients with kidney disease, as they may worsen kidney function 1.
• Atorvastatin is not commonly associated with AIN or the urinary abnormalities described in this case, however, it is not entirely clear if it has a direct effect on kidney function.
• Losartan, an angiotensin receptor blocker, can affect kidney function but typically doesn't cause the urinary findings seen here, and it is often used for kidney protection in patients with chronic kidney disease (CKD) 1.
• Amlodipine and omeprazole are not directly implicated in the kidney injury in this case, although omeprazole can cause AIN, the evidence suggests that naproxen is more likely the culprit. Discontinuing naproxen is the most appropriate first step in management, as it is the most likely cause of the patient's kidney injury.

From the FDA Drug Label

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance < 30 mL/min) The potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment

The patient has a serum creatinine level of 2.6 mg/dL, indicating renal impairment. Given the information from the drug label, naproxen should be discontinued in this patient due to the potential for renal toxicity and accumulation of metabolites. The correct option is D Naproxen and atorvastatin or E Naproxen and omeprazole, but since atorvastatin does not have a direct warning regarding renal impairment in the provided text, the most direct answer related to the question is E Naproxen and omeprazole is not the best choice, D is a better option because atorvastatin is not directly implicated in renal impairment in the provided label, but Naproxen is. However, considering the potential for drug interactions and renal effects, the best choice would be the option that includes Naproxen. Considering the potential for renal effects and the information provided in the label, the correct answer is D Naproxen and atorvastatin 2, 2, 2.

From the Research

Patient Presentation

The patient is a 46-year-old woman with a serum creatinine level of 2.6 mg/dL, which has increased from a baseline of 0.9 mg/dL three months ago. She is asymptomatic and has been taking losartan and amlodipine for hypertension, omeprazole for gastroesophageal reflux disease, naproxen for knee osteoarthritis, and atorvastatin for hyperlipidemia.

Urinalysis Results

The urinalysis shows:

• Specific gravity: 1.015
• pH: 5.5
• 1+ erythrocytes
• 3+ leukocytes
• 1+ leukocyte esterase
• No nitrates

• 100 leukocytes/hpf with leukocyte and granular casts

Relevant Studies

Studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause renal function abnormalities, including acute deterioration of renal function 3. Naproxen, in particular, has been associated with renal papillary necrosis and acute tubular necrosis 4, 5. The risk of acute kidney injury (AKI) is higher with non-selective NSAIDs, such as naproxen, compared to selective NSAIDs 6.

Drug Discontinuation

Based on the patient's presentation and the evidence from the studies, the drug that should be discontinued is naproxen, as it is a non-selective NSAID that can cause renal function abnormalities. Additionally, omeprazole is not directly related to the patient's renal function abnormality, but it is often used in combination with NSAIDs and can increase the risk of AKI. However, the most direct cause of the patient's renal function abnormality is likely naproxen.

Recommended Course of Action

The correct answer is:

• E Naproxen and omeprazole However, based on the provided evidence, naproxen is the most likely cause of the patient's renal function abnormality.
• Key points to consider:
  • Naproxen can cause renal papillary necrosis and acute tubular necrosis 4, 5
  • Non-selective NSAIDs, such as naproxen, have a higher risk of AKI compared to selective NSAIDs 6
  • The patient's urinalysis results show evidence of renal inflammation and damage, which is consistent with NSAID-induced renal injury 3, 7