A 54-year-old obese man was diagnosed with NIDDM 1 year earlier. He was staed on glipizide and metformin. His other medications are propranolol and nifedipine for hypeension, and naproxen, which he began 2 weeks ago for severe osteoahritis. His BP is 154/92. His BUN is 29 mg/dL and a creatinine of 1.8 mg/dL; both had been normal 1 year earlier. Which medications are most likely responsible for the increase in BUN and creatinine?

**Core Concept**
The underlying principle being tested is the understanding of drug-induced nephrotoxicity and its effects on renal function, particularly in the context of **nephrotoxic agents** and **renal hemodynamics**. This involves the impact of various medications on **glomerular filtration rate (GFR)** and **tubular function**.

**Why the Correct Answer is Right**
The correct answer involves medications that can impair renal function, either by reducing blood flow to the kidneys or by direct toxic effects on renal tissues. **Naproxen**, a nonsteroidal anti-inflammatory drug (NSAID), is known to cause **renal vasoconstriction**, reducing GFR and potentially increasing BUN and creatinine levels. **Nifedipine**, a calcium channel blocker, can also affect renal hemodynamics, although its effect is generally less pronounced than that of NSAIDs.

**Why Each Wrong Option is Incorrect**
**Option A:** Glipizide and metformin are not typically associated with nephrotoxicity; metformin is contraindicated in severe renal impairment but does not cause it.
**Option B:** Propranolol, a beta-blocker, is not directly nephrotoxic.
**Option C:** While nifedipine can affect renal function, its combination with another agent is more likely responsible for the observed changes.

**Clinical Pearl / High-Yield Fact**
It's crucial to remember that **NSAIDs** can significantly impair renal function, especially in patients with pre-existing renal issues or those taking other nephrotoxic agents. Monitoring renal function is essential when initiating NSAID therapy.

**Correct Answer:** D. naproxen and nifedipine

✓ Correct Answer: C. Naproxen