Management of Proton Pump Inhibitors in Patients with Chronic Kidney Disease

Introduction to PPI Use in CKD Patients

The American Journal of Kidney Diseases recommends gastroprotection for CKD patients on multiple medications that increase bleeding risk, such as antiplatelet agents, anticoagulants, and NSAIDs 1

Patients with previous GI events on aspirin should be treated with NSAID + PPI or COX2 + PPI, as recommended by the American Gastroenterological Association, American Heart Association, and European Society of Cardiology 2, 3
Patients on multiple antithrombotics, anticoagulants plus aspirin, or NSAIDs with additional risk factors should be considered for gastroprotection with PPIs, as suggested by the European Society of Cardiology and American Gastroenterological Association 2, 4, 5
Patients with atrial fibrillation requiring anticoagulation should be considered for gastroprotection with PPIs, as recommended by the Kidney International guidelines 6
Long-term use of PPIs is recommended for patients with Barrett's esophagus, clinically significant erosive esophagitis, and gastroprotection in high-risk patients using ASA/NSAIDs, as recommended by the American Gastroenterological Association 4
PPIs are conditionally indicated for long-term use in patients with PPI-responsive endoscopy-negative reflux disease with recurrence on PPI cessation and esophageal strictures from GERD (peptic strictures) 4

The lowest effective dose of PPIs should be used, as high doses increase the risk of incident CKD, with a hazard ratio of 1.92 (95% CI 1.00-6.19) 2
Regular monitoring of renal function is necessary in CKD patients on PPIs, with baseline eGFR measurement and follow-up eGFR at least every 3-6 months, as recommended by the National Kidney Foundation and American Gastroenterological Association 2, 4

The risk-benefit ratio of PPI therapy should be assessed based on the severity of CKD, duration of intended therapy, and presence of other risk factors for CKD progression, as suggested by the American College of Cardiology 2
The risk of incident CKD increases after 3 months of PPI exposure, with a hazard ratio of 1.78 (95% CI 1.39-2.25), and periodic reassessment of need is recommended, according to the Kidney International guidelines 6
Clinicians should consider de-prescribing PPIs in all patients without a definitive indication for chronic PPI use and use a step-down approach for patients on twice-daily dosing 4

Discontinuing PPIs in CKD patients may not significantly improve renal function after one year, and should be done with caution, as recommended by the European Renal Association 2
Potential drug interactions with PPIs should be monitored, as CKD patients are often on multiple medications, with a mean of 6.90±4.17 medications, according to the American Society of Nephrology 2
Clinicians should not discontinue PPIs in patients with complicated GERD or high risk for GI bleeding on antithrombotics or anticoagulants 4, 5
Clinicians should warn patients about potential rebound acid hypersecretion upon discontinuation of PPIs and monitor for drug interactions as CKD patients are often on multiple medications 4
Regular monitoring for signs of worsening kidney function and education about potential renal risks are essential for CKD patients on PPIs 4

The American College of Cardiology notes that omeprazole has potential interactions with medications commonly used in CKD patients through CYP2C19 inhibition, which may affect metabolism of clopidogrel, reducing its antiplatelet effect 7
The American College of Cardiology suggests considering pantoprazole as an alternative when drug interactions are a concern 7