Are Ras (Renin-Angiotensin System) inhibitors contraindicated in patients with Acute Kidney Injury (AKI)?

RAS Inhibitors in Acute Kidney Injury

RAS inhibitors (ACE inhibitors and ARBs) should be temporarily discontinued in patients with acute kidney injury (AKI) until renal function has returned to baseline or stabilized.

Pathophysiology of RAS Inhibitors in AKI

RAS inhibitors affect renal hemodynamics by:

• Causing efferent arteriolar dilation
• Decreasing transglomerular hydrostatic pressure
• Reducing glomerular filtration rate (GFR)
• Decreasing filtration fraction

In patients with AKI, these hemodynamic changes can worsen kidney function by further reducing already compromised glomerular filtration. This is particularly problematic in conditions of renal hypoperfusion.

Evidence-Based Recommendations for RAS Inhibitors in AKI

When to Discontinue RAS Inhibitors

• During active AKI episodes 1
• When serum creatinine increases >30% from baseline within the first 2 months of therapy 1
• In conditions of acute renal hypoperfusion 1
• In volume-depleted states (dehydration, diuretics, diarrhea, vomiting) 1
• In hemodynamic compromise (systemic hypotension with MAP <65 mmHg) 1
• During sepsis (which can worsen AKI severity when RAS inhibitors are continued) 2

High-Risk Scenarios Requiring Caution

• Bilateral renal artery stenosis or stenosis in a solitary kidney 3
• Concurrent use of nephrotoxic medications (NSAIDs, radiocontrast) 1
• Severe heart failure with reduced cardiac output 1
• Patients receiving contrast media for imaging studies 4

Management Algorithm for RAS Inhibitors in AKI

1. Assess AKI severity and cause

   • Determine if AKI is related to volume depletion, hemodynamic changes, or nephrotoxicity
   • Check baseline and current creatinine levels

2. Discontinue RAS inhibitors if:

   • Active AKI is present
   • Serum creatinine has increased >30% from baseline 1
   • Patient is volume depleted or hemodynamically unstable
   • Hyperkalemia is present (K+ >5.6 mmol/L) 1

3. Supportive care during AKI:

   • Correct volume status
   • Optimize blood pressure (maintain MAP >65 mmHg)
   • Discontinue other nephrotoxic medications
   • Monitor electrolytes, particularly potassium

4. Restarting RAS inhibitors after AKI resolution:

   • Wait until renal function has returned to baseline or stabilized 1
   • Ensure adequate volume status is achieved
   • Verify blood pressure is adequate (MAP >65 mmHg)
   • Consider starting at a lower dose and titrating up

Special Considerations

Expected Changes in Renal Function with RAS Inhibitors

• A 10-20% increase in serum creatinine after starting RAS inhibitors is expected and acceptable 1
• Do not discontinue RAS inhibitors for this expected mild increase in creatinine

Long-Term Benefits Despite Initial Creatinine Rise

• RAS inhibitors provide long-term renoprotection in chronic kidney disease 1
• Restarting RAS inhibitors after AKI resolution is associated with lower long-term mortality (adjusted HR of 0.85,95% CI 0.81-0.89) 1

Common Pitfalls to Avoid

• Inappropriate discontinuation for small (10-20%) rises in creatinine 1
• Substituting ARBs for ACE inhibitors during AKI recovery, as both exert similar effects on renal hemodynamics 1
• Overlooking the need to restart RAS inhibitors after AKI resolution, which can provide long-term benefits 5
• Continuing RAS inhibitors during sepsis-associated AKI, which can lead to more severe kidney injury (RRR 2.32,95% CI 1.50-3.59 for stage 3 AKI) 2

Monitoring Recommendations

• Regular assessment of renal function and potassium levels
• Vigilant monitoring when restarting RAS inhibitors after AKI resolution
• Avoid concurrent nephrotoxic medications
• Reassess medication regimen as renal function changes

By following these evidence-based recommendations, clinicians can appropriately manage RAS inhibitors in patients with AKI to optimize outcomes while minimizing risks of worsening kidney function.