A 73-year-old man with a 10-year history of chronic kidney disease (GFR 25 mL/min) and hypertension presents to his primary care physician for a routine follow-up. He has been on lisinopril 10 mg daily for blood pressure control, and his creatinine has remained stable at 2.1 mg/dL over the past year. His blood pressure today is 138/84 mmHg, heart rate is 72 bpm, and he has trace bilateral lower extremity edema. Two weeks ago, his rheumatologist added ibuprofen 400 mg three times daily for worsening bilateral knee arthralgias. Repeat laboratory work now reveals a creatinine of 2.8 mg/dL, BUN of 48 mg/dL, and a potassium of 5.3 mEq/L. Urinalysis shows no casts or proteinuria. Which of the following best explains this acute decline in renal function?

1. A)NSAIDs inhibit prostaglandin-mediated afferent arteriolar vasodilation; combined with ACE inhibitor-mediated efferent vasoconstriction, GFR drops criticallyGABARITO
2. B)NSAIDs displace lisinopril from renal tissue protein binding, causing acute accumulation
3. C)Lisinopril activates intrarenal angiotensin II production, worsening NSAID-induced vasoconstriction
4. D)NSAIDs cause direct tubular toxicity independent of hemodynamic changes
5. E)NSAIDs and lisinopril competitively inhibit renal blood flow at different arteriolar sites