What is the preferred Proton Pump Inhibitor (PPI) for patients with Chronic Kidney Disease (CKD)?

Preferred PPI in CKD Patients

No specific PPI is preferred over another in CKD patients based on current guideline evidence, but all PPIs should be used cautiously and only when clearly indicated due to their association with CKD progression and adverse renal outcomes. 1

Guideline Recommendations for PPI Use in CKD

The most recent KDIGO 2024 guidelines mention PPI use only in the context of gastrointestinal bleeding prophylaxis when patients are on antiplatelet therapy or anticoagulation, not as a general recommendation. 1 Specifically:

• PPIs are recommended for patients at high risk of gastrointestinal bleeding who are receiving aspirin monotherapy, dual antiplatelet therapy (DAPT), or oral anticoagulation monotherapy. 1
• The guidelines do not specify which PPI to use or provide dosing recommendations specific to CKD stages. 1

Critical Safety Concerns with PPIs in CKD

Evidence of Harm

Multiple studies demonstrate concerning associations between PPI use and renal outcomes:

• PPI use is associated with incident CKD, CKD progression, acute kidney injury, acute interstitial nephritis, and increased mortality in patients with kidney disease. 2, 3
• CKD patients are prescribed PPIs more frequently and for longer durations than non-CKD patients (median 120 days in CKD stage 3-4 vs 90 days in non-CKD patients). 4
• PPIs increase indoxyl sulfate synthesis (a uremic toxin) by inhibiting CYP2E1 protein degradation, which may mechanistically explain CKD progression. 5

Lack of Benefit from Discontinuation

• Discontinuing PPIs in established CKD patients does not improve renal function after 1 year of follow-up, suggesting the damage may be irreversible once established. 6

Practical Approach to PPI Selection in CKD

When PPIs Are Indicated

Use PPIs only for clear indications:

• Active gastrointestinal bleeding or high bleeding risk with antiplatelet/anticoagulation therapy 1
• Documented peptic ulcer disease
• Severe gastroesophageal reflux disease unresponsive to other measures
• Zollinger-Ellison syndrome

Choosing a Specific PPI

Since no PPI has proven superiority in CKD, selection should be based on:

• Standard dosing without need for renal adjustment: All PPIs (omeprazole, lansoprazole, pantoprazole, esomeprazole, rabeprazole) can be used at standard doses across all CKD stages, as they are primarily hepatically metabolized. 2
• Cost and formulary availability: Choose the most cost-effective option available
• Once-daily dosing preferred over twice-daily: Higher dosing frequency is associated with greater CKD risk (adjusted HR 1.46 for twice-daily vs 1.15 for once-daily). 3

Critical Pitfall to Avoid

The most important consideration is avoiding PPI-associated hypomagnesemia, which compounds the renal magnesium wasting already present in some CKD patients. 1 If hypomagnesemia develops on a PPI:

• Switch to H2 receptor antagonists (ranitidine alternatives like famotidine) 1
• Monitor magnesium levels regularly in CKD patients on PPIs 1

Deprescribing Strategy

Actively deprescribe PPIs when not clearly indicated:

• Review PPI necessity at every visit in CKD patients, as they are frequently used without medical indication and rarely deprescribed. 2
• Attempt step-down therapy: Reduce to lowest effective dose or transition to on-demand use 2
• Consider H2 receptor antagonists as alternatives when acid suppression is still needed but PPI risks outweigh benefits 1
• Do not expect renal function improvement from discontinuation in established CKD, but prevent further progression. 6

Monitoring Recommendations

For CKD patients requiring ongoing PPI therapy:

• Monitor serum magnesium levels every 3-6 months 1
• Reassess indication at each clinical encounter 2
• Limit duration to the shortest necessary period 4, 2
• Monitor for signs of acute interstitial nephritis: fever, rash, eosinophilia, acute kidney injury 2