Should irbesartan (Angiotensin II Receptor Blocker) be held in a patient with Acute Kidney Injury (AKI)?

Should Irbesartan Be Held in Acute Kidney Injury?

Yes, irbesartan should be temporarily suspended during acute kidney injury (AKI). Multiple guideline societies, including KDOQI and the American College of Cardiology, explicitly recommend temporarily suspending RAAS antagonists like irbesartan during high-risk periods including intercurrent illness, and the FDA label warns that drugs inhibiting the renin-angiotensin system can cause changes in renal function including acute renal failure, particularly in patients whose renal function depends on this system 1, 2.

Rationale for Suspension

ARBs like irbesartan directly worsen kidney function during AKI through hemodynamic mechanisms. Irbesartan blocks angiotensin II receptors, preventing efferent arteriolar constriction that normally maintains glomerular filtration pressure. During AKI, when renal perfusion is already compromised, this blockade decreases the pressure gradient across glomerular capillaries and further reduces GFR 1, 3.

The FDA label specifically states: "Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system may be at particular risk of developing acute renal failure on irbesartan. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on irbesartan" 2.

When to Hold Irbesartan

Suspend irbesartan immediately when:

• AKI is diagnosed (serum creatinine increase ≥0.3 mg/dL within 48 hours or ≥1.5 times baseline within 7 days) 1
• Volume depletion is present (patients on high-dose diuretics, vomiting, diarrhea) 2, 4
• Planned procedures occur: IV radiocontrast administration, bowel preparation for colonoscopy, major surgery 1
• Intercurrent illness develops (sepsis, heart failure exacerbation, severe dehydration) 1

Alternative Antihypertensive Options During AKI

Use calcium channel blockers as first-line alternatives during AKI. Dihydropyridines like amlodipine (2.5-10 mg daily) have minimal effects on renal hemodynamics and do not compromise glomerular filtration pressure 1, 3.

Additional alternatives based on clinical context:

• Loop diuretics (furosemide) for volume overload with moderate-to-severe kidney dysfunction 1
• Beta-blockers if concomitant ischemic heart disease or heart failure exists 1
• Thiazide-like diuretics (chlorthalidone) only in mild AKI with GFR >30 mL/min 1

When to Restart Irbesartan After AKI

Wait for three specific conditions before reintroducing irbesartan:

1. GFR stabilization - Serum creatinine has plateaued or is improving for at least 48-72 hours 1, 3
2. Volume status optimization - Patient is euvolemic without ongoing losses 1, 2
3. Resolution of acute illness - Sepsis resolved, hemodynamics stable without vasopressors 1

Restart Protocol

Start with lower doses and monitor aggressively:

• Begin at 75 mg daily (half the usual starting dose) 1
• Check serum creatinine and potassium within 1 week of restarting 1, 3
• Accept creatinine increases up to 30% from the new baseline as expected hemodynamic effects 3
• Hold if potassium rises above 5.5 mEq/L 1

Critical Contraindications to Restarting

Do not restart irbesartan if:

• Serum potassium >5.5 mEq/L 1
• Mean arterial pressure <65 mm Hg 1
• Bilateral renal artery stenosis or stenosis in solitary kidney 3, 5
• Ongoing volume depletion 2, 4

Common Pitfalls to Avoid

Never combine irbesartan with ACE inhibitors or direct renin inhibitors after AKI, as this substantially increases hyperkalemia and hypotension risk 1.

Avoid potassium supplements or potassium-sparing diuretics when restarting irbesartan, as hyperkalemia requiring discontinuation occurred in patients with renal impairment 1, 6.

Do not confuse hemodynamic creatinine rises with true kidney injury. Creatinine increases up to 30% represent altered renal hemodynamics rather than tubular damage and do not show positive injury biomarkers like NGAL or KIM-1 3. However, during active AKI, this distinction is irrelevant—irbesartan should still be held.

Important Exception

KDOQI guidelines state that RAAS antagonists should not be routinely discontinued in stable patients with GFR <30 mL/min/1.73 m² as they remain nephroprotective 1. This applies to chronic kidney disease, not acute kidney injury. The distinction is critical: hold during AKI episodes, but maintain in stable advanced CKD.