In a 72‑year‑old man with hypertension, type‑2 diabetes and on enalapril who recently started etoricoxib, is his acute decompensation precipitated by chronic kidney disease?

Is CKD the Precipitant? No—The Acute Decompensation Is Precipitated by Etoricoxib in the Context of Multiple Nephrotoxic Exposures

The acute decompensation in this patient is precipitated by the recent addition of etoricoxib, not by his underlying chronic kidney disease. The combination of an NSAID (etoricoxib), an ACE inhibitor (enalapril), and his baseline risk factors (hypertension, diabetes) creates a "triple whammy" that dramatically increases the risk of acute kidney injury and hyperkalemia. 1, 2

Why Etoricoxib Is the Culprit

Each additional nephrotoxic medication raises the odds of developing AKI by approximately 53%, and exposure to three or more nephrotoxins more than doubles the risk. 3, 1 In this patient:

• Etoricoxib (COX-2 inhibitor) blocks prostaglandin-mediated afferent arteriolar vasodilation, reducing renal perfusion 4, 5
• Enalapril (ACE inhibitor) blocks angiotensin II-mediated efferent arteriolar vasoconstriction, reducing filtration pressure 1, 4, 6
• Combined effect: When both mechanisms are blocked simultaneously, glomerular filtration becomes critically compromised, precipitating acute kidney injury 4, 2

The Clinical Evidence

A directly analogous case report documents life-threatening hyperkalemia and acute kidney dysfunction precipitated by etoricoxib in a patient on an angiotensin receptor blocker (telmisartan), with similar baseline risk factors. 2 The patient's condition resolved completely when etoricoxib was discontinued, but recurred when other medications were restarted without etoricoxib, confirming causality. 2

Immediate Management Algorithm

Step 1: Discontinue the nephrotoxin immediately

• Stop etoricoxib permanently—NSAIDs should be discontinued completely, not merely held, during AKI 1

Step 2: Temporarily hold the ACE inhibitor

• Suspend enalapril as soon as AKI is diagnosed to prevent further reduction in glomerular filtration pressure 1
• Do not permanently discontinue—permanent withdrawal after AKI increases 30-day mortality due to hypertensive rebound 1

Step 3: Assess volume status

• If serum creatinine has doubled from baseline, administer albumin 1 g/kg/day for 2 days 1
• Monitor urine output and vital signs closely 1

Step 4: Monitor renal function and electrolytes

• Measure serum creatinine and potassium every 48 hours during the acute phase 7, 1

When to Restart Enalapril

Restart enalapril only when ALL of the following criteria are met: 1

• Estimated GFR has stabilized
• Volume status is optimized
• Mean arterial pressure > 65 mmHg
• Serum potassium < 5.5 mmol/L

Begin at lower-than-usual doses and recheck renal function and potassium within one week. 1

Critical Pitfall to Avoid

The FDA label explicitly warns that co-administration of NSAIDs with ACE inhibitors in patients who are elderly, volume-depleted, or have compromised renal function may result in deterioration of renal function, including possible acute renal failure. 4 This patient has multiple risk factors (age 72, diabetes, hypertension) that made him particularly vulnerable. 7, 3

Do not attribute this acute event to "progression of CKD"—this is a preventable, drug-induced acute kidney injury. The underlying CKD is a risk factor that made him susceptible, but etoricoxib is the precipitant. 3, 2

Long-Term Prevention

• Never restart etoricoxib or any other NSAID in this patient 1, 4
• Educate the patient to hold enalapril during future episodes of volume depletion (vomiting, diarrhea, excessive sweating) to prevent recurrent AKI 1, 4
• Avoid potassium-containing salt substitutes while on enalapril 4