Does Angiotensin Receptor Blocker (ARB) worsen Acute Kidney Injury (AKI)?

Does ARB Worsen Acute Kidney Injury?

ARBs do not worsen true acute kidney injury (AKI), but they can cause hemodynamic changes that reduce glomerular filtration and increase serum creatinine up to 30% from baseline—this is NOT AKI and should not be confused with kidney injury. 1

Understanding the Critical Distinction

The most important concept is distinguishing between hemodynamic creatinine elevation and true AKI:

• Small creatinine increases (up to 30% from baseline) with ARBs are expected hemodynamic effects and do not represent actual kidney injury or damage 1
• Analysis of the ACCORD BP trial demonstrated that patients with up to 30% creatinine increases had no increase in mortality or progressive kidney disease 1
• Biomarkers of actual kidney injury showed no significant elevation despite creatinine rises, confirming these are hemodynamic rather than injurious changes 1

When ARBs Should NOT Be Discontinued

ARBs should not be stopped for creatinine increases <30% in the absence of volume depletion 1:

• The hemodynamic creatinine rise reflects reduced intraglomerular pressure, which is actually the mechanism of long-term kidney protection 1
• All clinical trials demonstrating ARB efficacy in slowing CKD progression used maximally tolerated doses, not low doses 1
• Underdosing ARBs due to fear of creatinine elevation is a common error that deprives patients of proven mortality and kidney protection benefits 1

When ARBs May Contribute to AKI Risk

ARBs can reduce intravascular volume, renal blood flow, and glomerular filtration, which may contribute to AKI in specific high-risk scenarios 1:

• During volume depletion states (diarrhea, vomiting, inadequate oral intake) 2
• Perioperative period when combined with other hemodynamic stressors 3
• Acute illness with reduced effective volume (sepsis, heart failure decompensation) 2
• When combined with other nephrotoxins (NSAIDs, contrast agents) 3

The American College of Cardiology and guideline societies recommend temporarily suspending ARBs during high-risk periods including intercurrent illness, IV radiocontrast administration, bowel preparation, and major surgery 4

Evidence on ARB Continuation During AKI

Recent research challenges traditional practice of routine ARB discontinuation:

• A multicenter prospective study found no association between acute ARB exposure and persistent acute kidney disease after AKI 5
• Meta-analysis of 70,801 patients showed ARB users after AKI had lower all-cause mortality (OR 0.69) and lower recurrent AKI risk (OR 0.78) compared to non-users 6
• Patients continuing ARBs after AKI had lower mortality risk than those who discontinued them 6, 7
• ARB continuation was associated with reduced progression to incident CKD 6

Practical Management Algorithm

During Active AKI:

1. Assess volume status first - if volume depleted, temporarily hold ARB and restore euvolemia 4
2. If euvolemic with creatinine rise <30%: continue ARB at current dose 1
3. If creatinine rise >30%: temporarily suspend ARB until stabilization 4
4. Monitor potassium - hold if K+ >5.5 mEq/L 4, 8

After AKI Resolution:

1. Wait for GFR stabilization and volume optimization before reintroducing 4, 8
2. Start with lower doses (e.g., candesartan 4-8 mg, valsartan 40 mg) 8
3. Recheck renal function and potassium within 1 week of restart 4, 8
4. Accept creatinine increases up to 30% without discontinuation if K+ remains <5.5 mEq/L 1

Critical Pitfalls to Avoid

• Do not confuse hemodynamic creatinine elevation with AKI - this leads to inappropriate ARB discontinuation and loss of proven benefits 1
• Do not underdose ARBs due to creatinine concerns - maximally tolerated doses are required for kidney protection 1
• Do not routinely discontinue ARBs in patients with eGFR <30 mL/min/1.73 m² - they remain nephroprotective even at advanced CKD stages 1
• Do not restart ARBs if hyperkalemia (K+ >5.5 mEq/L) persists 4, 8

Monitoring Requirements

For patients on ARBs with eGFR <60 mL/min/1.73 m²:

• Monitor serum potassium periodically 1
• Assess creatinine and eGFR annually at minimum 1
• After ARB restart post-AKI: check within 1 week 4, 8

The evidence strongly supports that ARBs themselves do not cause or worsen true AKI, though they require temporary suspension during volume-depleted states and careful monitoring during reintroduction.