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

Proton Pump Inhibitors in Chronic Kidney Disease: Recommendations and Risks

Proton pump inhibitors (PPIs) should be used with caution in patients with chronic kidney disease (CKD), with careful consideration of indication, duration, and monitoring for adverse effects, as they are associated with increased risk of CKD progression.

Risk Assessment and Association with CKD

Recent evidence suggests a concerning relationship between PPI use and kidney disease:

• Observational studies have linked PPI use with increased risk of acute kidney injury, acute interstitial nephritis, incident CKD, CKD progression, and end-stage kidney disease 1, 2, 3
• Meta-analysis data shows PPI use is significantly associated with an increased risk of CKD (RR 1.72,95% CI: 1.02-2.87) 3
• CKD patients are prescribed PPIs for longer durations compared to non-CKD patients (median 120 days vs. 90 days) 4

Indications for PPI Use in CKD Patients

Despite risks, there are specific situations where PPI use is recommended in CKD patients:

• For liver transplant candidates on dual antiplatelet therapy (DAPT) to reduce gastrointestinal bleeding risk 5
• For patients with atrial fibrillation requiring anticoagulation, PPIs are recommended when managing bleeding risk 5
• For patients with established gastroesophageal reflux disease (GERD) requiring treatment 6

Monitoring and Management Recommendations

When PPIs are necessary for CKD patients:

1. Assess indication carefully:

   • Ensure there is a clear and appropriate indication for PPI therapy
   • Avoid inappropriate or unclear indications 1

2. Use lowest effective dose:

   • Prescribe the minimum effective dose needed to control symptoms 1
   • Consider dose adjustment based on CKD stage

3. Limit duration:

   • Implement regular reassessment of continued necessity 2
   • Consider deprescribing when appropriate

4. Monitor kidney function:

   • Regular monitoring of estimated glomerular filtration rate (eGFR)
   • Watch for signs of acute kidney injury or CKD progression 2

5. Monitor for other adverse effects:

   • Check magnesium levels periodically (hypomagnesemia is a known risk) 6
   • Monitor for Clostridium difficile infection 5, 6
   • Consider bone health (increased fracture risk with long-term use) 6

Deprescribing Considerations

For patients already on PPIs:

• Evaluate the risk-benefit ratio regularly
• Consider gradual tapering rather than abrupt discontinuation to prevent rebound acid hypersecretion 6
• One study showed no significant improvement in renal function after PPI discontinuation in CKD patients after one year, suggesting that damage may not be readily reversible 7

Special Populations

For elderly CKD patients:

• PPIs are considered potentially inappropriate medications (PIMs) in older people 5
• If used for >12 weeks, clinical rationale should support an underlying chronic disease (e.g., GERD) or risk factors (e.g., chronic NSAID use) 5

For patients on multiple medications:

• CKD patients often take more medications simultaneously (6.90±4.17 vs. 4.54±2.43 in non-CKD patients) 4
• Consider drug interactions and cumulative medication burden

Conclusion

While PPIs have important therapeutic roles in specific clinical scenarios for CKD patients, their use requires careful consideration of risks and benefits. The association between PPIs and kidney disease progression warrants a cautious approach with appropriate monitoring and regular reassessment of continued necessity.