What are the guidelines for using Proton Pump Inhibitors (PPIs) in patients with Chronic Kidney Disease (CKD)?

Guidelines for Using Proton Pump Inhibitors in Patients with Chronic Kidney Disease

PPIs should be used in CKD patients only when there is a clear indication, with regular monitoring of renal function and consideration of the lowest effective dose for the shortest duration necessary.

Appropriate Indications for PPI Use in CKD Patients

The use of PPIs in CKD patients should be limited to specific evidence-based indications:

• Definitive indications 1:

  • Barrett's esophagus
  • Clinically significant erosive esophagitis
  • Gastroprotection in high-risk patients using ASA/NSAIDs
  • PPI-responsive endoscopy-negative reflux disease with recurrence on PPI cessation
  • Esophageal strictures from GERD

• Gastroprotection indications 1, 2:

  • Patients on multiple antithrombotics
  • Patients on anticoagulants plus aspirin
  • Patients on NSAIDs with additional risk factors
  • Patients with atrial fibrillation requiring anticoagulation 2

Risk Assessment and Monitoring

1. Document clear indication for PPI therapy in all CKD patients 1

2. Regular monitoring of renal function in CKD patients on PPIs 1

   • Baseline eGFR measurement
   • Follow-up eGFR at least every 3-6 months

3. Assess risk-benefit ratio based on:

   • Severity of CKD (stage)
   • Duration of intended therapy
   • Presence of other risk factors for CKD progression

Dosing Considerations

Evidence suggests higher risk with higher doses and longer duration:

• Use lowest effective dose as high doses increase risk of incident CKD (HR 1.92; 95% CI 1.00-6.19) 3

• Duration considerations:

  • Risk of incident CKD increases after 3 months of exposure (HR 1.78; 95% CI 1.39-2.25) 3
  • Consider periodic reassessment of need after 3 months

Special Situations

1. Patients requiring gastroprotection 2:

   • For patients with previous GI events on aspirin: NSAID + PPI or COX2 + PPI is appropriate 2
   • For liver transplant candidates on dual antiplatelet therapy: PPIs are recommended to reduce GI bleeding 2

2. Patients with established CKD:

   • CKD patients are often prescribed PPIs for longer durations than non-CKD patients (median 120 days vs. 90 days) 4
   • Consider de-prescribing PPIs in patients without definitive indications 1

Deprescribing Approach

When discontinuing PPIs in CKD patients:

• Use a step-down approach for patients on twice-daily dosing 1
• Warn patients about potential rebound acid hypersecretion 1
• Monitor for return of symptoms requiring PPI therapy

Important Caveats and Pitfalls

1. Association with CKD progression:

   • Regular PPI use is associated with a 37% higher risk of CKD incidence compared to non-users (HR 1.37,95% CI 1.28-1.47) 5
   • Signal strength is stronger for CKD (ROR = 8.80) than for AKI (ROR = 3.95) 6

2. Drug interactions:

   • CKD patients are often on multiple medications (6.90±4.17 vs 4.54±2.43 in non-CKD patients) 4
   • Monitor for potential drug interactions with PPIs

3. Discontinuation effects:

   • Discontinuing PPIs after prolonged use in CKD patients may not significantly improve renal function after one year 7
   • Do not discontinue PPIs in patients with complicated GERD or high risk for GI bleeding on antithrombotics/anticoagulants 1

By following these guidelines, clinicians can optimize the use of PPIs in CKD patients, balancing the necessary therapeutic benefits against potential risks to kidney function.