Are proton pump inhibitors (PPIs) bad for your kidneys?

Proton Pump Inhibitors and Kidney Health

PPIs are associated with an increased risk of kidney problems including acute interstitial nephritis and chronic kidney disease, but should not be discontinued if there is a valid medical indication for their use.

Kidney Risks Associated with PPIs

• PPIs have been linked to several kidney-related adverse effects including acute tubulointerstitial nephritis, which can occur at any time during treatment 1, 2
• Long-term PPI use is associated with increased risk of chronic kidney disease, kidney disease progression, and kidney failure 3, 4
• A meta-analysis of observational studies found PPI use was significantly associated with a 72% increased risk of chronic kidney disease compared to non-PPI users 4
• PPI use is associated with chronic renal outcomes even in the absence of intervening acute kidney injury 5

Mechanism of Kidney Damage

• Acute tubulointerstitial nephritis (TIN) is the most well-documented kidney complication of PPIs 1
• Patients with TIN may present with varying signs and symptoms from hypersensitivity reactions to non-specific symptoms of decreased renal function (malaise, nausea, anorexia) 1
• Some patients may be diagnosed on biopsy without extra-renal manifestations such as fever, rash, or arthralgia 1
• The mechanism appears to be a class effect as all PPIs have been documented to cause acute interstitial nephritis 6

Monitoring and Risk Mitigation

• Monitor for decreased urine output or blood in the urine, which may indicate kidney problems 1, 2
• Patients with pre-existing renal disease, congestive heart failure, or cirrhosis may be at higher risk for renal complications 7
• Consider periodic monitoring of renal function in high-risk patients, especially those taking other medications that might decrease renal function (such as ACE inhibitors or angiotensin receptor blockers) 7
• If signs or symptoms of kidney problems develop, discontinue the PPI and refer for appropriate evaluation 1

Recommendations for PPI Use

• All patients taking a PPI should have regular review of the ongoing indications for use 7, 8
• Primary care providers should be primarily responsible for reviewing the presence of ongoing indications for PPI use and identifying candidates for de-prescribing 7, 9
• Patients without a definitive indication for chronic PPI use should be considered for trial of de-prescribing 7, 9
• Most patients with twice-daily dosing should be considered for step-down to once-daily PPI 7, 9
• Use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated 1

When Not to Discontinue PPIs

• Patients with complicated GERD, such as those with severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation 7, 9
• Other definite indications for long-term use include Barrett's esophagus, gastroprotection in high-risk NSAID/aspirin users, and Zollinger-Ellison Syndrome 9
• The decision to discontinue PPIs should be based on lack of indication for use, not solely due to concerns about potential adverse events 8
• Discontinuing PPIs in patients with definite indications based on concerns about unproven risks may lead to recurrent symptoms and serious complications 8

Clinical Perspective

• While observational studies show associations between PPI use and kidney problems, randomized controlled trials comparing PPIs with placebo have not shown a higher rate of adverse events among PPI users 7, 8
• The benefits of PPIs in treating conditions like erosive esophagitis, peptic ulcer disease, and Barrett's esophagus may outweigh the potential risks in appropriate patients 9
• The risk-benefit assessment should be individualized based on the specific indication for PPI use, presence of risk factors for kidney disease, and availability of alternative treatments 7
• When deprescribing PPIs, either dose tapering or abrupt discontinuation can be considered 8