Can I give a Proton Pump Inhibitor (PPI) to someone with Acute Kidney Injury (AKI)?

Administering Proton Pump Inhibitors in Patients with Acute Kidney Injury

PPIs should be avoided in patients with AKI unless there is a compelling clinical indication with no suitable alternatives available, as they are associated with increased risk of worsening kidney function and progression to chronic kidney disease.

Risk Assessment for PPI Use in AKI

The decision to use PPIs in patients with AKI should follow this algorithm:

1. Evaluate necessity of PPI therapy:

   • Is there a clear, urgent indication (active GI bleeding, severe GERD, etc.)?
   • Are there less nephrotoxic alternatives available (H2 blockers)?

2. Assess AKI stage and trajectory:

   • Is the patient recovering, stable, or worsening?
   • What is the current eGFR and trend?

3. Consider risk factors for PPI-related kidney injury:

   • Pre-existing CKD
   • Multiple nephrotoxic medications
   • Advanced age
   • Hemodynamic instability

Evidence for Concern

Current evidence shows significant concerns with PPI use in patients with kidney injury:

• PPIs are associated with both acute kidney injury and chronic kidney disease, with stronger signals for progression to CKD (ROR = 8.80) than for AKI (ROR = 3.95) 1.

• PPI use increases the risk of ESRD in patients with renal disease (adjusted OR = 1.88) 2.

• Even in the absence of intervening AKI, PPI use is associated with increased risk of eGFR decline, incident CKD, and progression to ESRD 3.

• In patients who have recovered from AKI requiring dialysis, PPI use is associated with higher risk of ESRD (sHR 1.40) 4.

Specific Recommendations

When to Absolutely Avoid PPIs in AKI:

• Active or worsening AKI
• Multiple concurrent nephrotoxic medications
• History of PPI-associated interstitial nephritis
• AKI requiring dialysis

When PPIs Might Be Considered (with caution):

• Life-threatening GI bleeding
• Severe stress ulcer prophylaxis in critical illness when H2 blockers are contraindicated
• High-risk variceal bleeding in portal hypertension

Monitoring if PPI Must Be Used

If a PPI must be used in a patient with AKI:

1. Use the lowest effective dose for the shortest duration
2. Monitor renal function closely (daily in hospitalized patients)
3. Watch for signs of worsening kidney function
4. Consider switching to H2 blockers as soon as clinically appropriate

Differences Between PPI Agents

Different PPIs may carry varying risks:

• Lansoprazole shows the strongest association with AKI 5
• Dexlansoprazole demonstrates stronger associations for both CKD (ROR = 34.94) and AKI (ROR = 8.18) than other PPIs 1
• Rabeprazole has been associated with the shortest time to AKI onset (median 9 days) 5

Key Principles from Guidelines

The KDIGO guidelines emphasize that drug selection in AKI should be guided by:

• Renal versus non-renal excretion
• Potential for nephrotoxicity
• Effect of AKI on drug metabolism
• Availability of suitable alternatives 6

Common Pitfalls to Avoid

1. Assuming PPIs are universally safe: Despite their common use, PPIs have significant nephrotoxic potential.

2. Failing to recognize the long-term risks: PPI-associated kidney injury can occur without obvious acute symptoms, with a median time to CKD of 177 days 1.

3. Missing the connection: Not recognizing that new or worsening kidney dysfunction may be related to PPI use.

4. Inadequate monitoring: Failing to monitor renal function in patients on PPIs with risk factors for kidney disease.

5. Overlooking alternatives: Not considering H2 blockers or other acid-suppression strategies when appropriate.