Should Irbesartan (Angiotensin II Receptor Antagonist) be stopped in patients with Acute Kidney Injury (AKI)?

Should Irbesartan Be Stopped in Acute Kidney Injury?

Yes, irbesartan should be temporarily suspended during acute kidney injury (AKI), but this is a temporary measure during the acute phase—not a permanent discontinuation.

Rationale for Temporary Suspension

The FDA label for irbesartan explicitly states that "changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system" and recommends to "consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on irbesartan" 1. This is particularly critical because ARBs directly affect renal hemodynamics by blocking angiotensin II receptors, which decreases glomerular filtration pressure and can further compromise already impaired kidney function 2.

When to Suspend Irbesartan

Suspend irbesartan immediately when:

• AKI is diagnosed (stage 2 or 3, or any clinically significant AKI) 3
• During intercurrent illness that may precipitate AKI 4
• Prior to planned IV radiocontrast administration 4
• Before bowel preparation prior to colonoscopy 4
• Prior to major surgery 4
• In the setting of volume depletion or salt depletion 1

The KDOQI guidelines specifically recommend temporarily suspending RAAS antagonists (including ARBs like irbesartan) during these high-risk periods 4.

Critical Caveat: Do Not Routinely Discontinue Permanently

The most important clinical pitfall is permanent discontinuation. KDOQI guidelines explicitly state: "Do not routinely discontinue in people with GFR < 30 ml/min/1.73 m² as they remain nephroprotective" 4. This applies to chronic kidney disease, but the principle extends to AKI recovery.

Recent observational data from over 10,000 patients who experienced moderate-to-severe AKI showed that stopping RASi after AKI was associated with:

• 13% increased risk of the composite outcome of death, MI, and stroke (HR 1.13,95% CI 1.07-1.19) 3
• Similar risk of recurrent AKI compared to continuing (HR 0.94,95% CI 0.84-1.05) 3
• Lower risk of hyperkalemia (HR 0.79,95% CI 0.71-0.88) 3

This means that while temporary suspension during acute illness is appropriate, permanent discontinuation deprives patients of cardiovascular benefits without reducing recurrent AKI risk 3.

Algorithm for Reintroduction After AKI

Step 1: Wait for stabilization

• GFR has stabilized (not necessarily returned to baseline) 2
• Volume status is optimized 2
• No ongoing acute illness 4

Step 2: Assess within 1 week of restarting

• Check GFR and serum potassium within 1 week of restarting 4
• Monitor for any dose escalation 4

Step 3: Start low and titrate slowly

• Begin with lower doses than pre-AKI 2
• Titrate slowly while monitoring renal function and potassium 2

Step 4: Consider patient-specific factors

• Patients with renal artery stenosis, severe heart failure, or chronic volume depletion require closer monitoring 1
• Those on other nephrotoxic drugs need more frequent assessment 2

Alternative Antihypertensives During AKI

If blood pressure control is needed during the AKI phase:

• First choice: Calcium channel blockers (amlodipine) have minimal effects on renal hemodynamics 2
• Second choice: Beta-blockers if concomitant ischemic heart disease or heart failure 2
• Third choice: Loop diuretics (furosemide) if volume overload present 2

Special Monitoring Requirements

The FDA label emphasizes that irbesartan requires periodic monitoring of renal function, particularly in patients whose renal function may depend on the renin-angiotensin system 1. During AKI, this monitoring becomes critical, and the threshold for temporary suspension should be low 1.

Pharmacokinetic Considerations

Irbesartan pharmacokinetics are not significantly altered by renal impairment, and the drug is not cleared by hemodialysis 5. This means dose adjustment based purely on GFR is not necessary, but the hemodynamic effects on the kidney remain the primary concern 5, 6.