What is the relationship between Proton Pump Inhibitors (PPIs) and Chronic Kidney Disease (CKD)?

From the Guidelines

Proton pump inhibitors (PPIs) should be used with caution in patients with chronic kidney disease (CKD) due to potential risks of worsening kidney function, as highlighted in a recent expert review published in Gastroenterology in 2022 1. When considering the use of PPIs in CKD patients, it is essential to weigh the benefits against the potential risks, including chronic kidney disease, fracture, dementia, and COVID-19 [ 1 ]. While the current evidence is based on observational studies and cannot establish causality, it is crucial to exercise caution when prescribing PPIs to CKD patients. Some key points to consider when using PPIs in CKD patients include:

• Limiting PPI use to the lowest effective dose and only when clearly indicated
• Considering alternative acid suppression therapies, such as H2 blockers like famotidine, when appropriate
• Regular monitoring of kidney function, with assessment every 3-6 months depending on CKD stage
• Being aware of the potential mechanisms behind PPI-associated kidney injury, including acute interstitial nephritis, hypomagnesemia, and recurrent acute kidney injury leading to chronic damage
• Tapering PPIs gradually when discontinuing long-term therapy to prevent rebound acid hypersecretion, typically by reducing to the lowest dose for 1-2 weeks before stopping or switching to as-needed use [ 1 ].

From the FDA Drug Label

A type of kidney problem (acute tubulointerstitial nephritis) Some people who take proton pump inhibitor (PPI) medicines, including lansoprazole delayed-release capsules, may develop a kidney problem called acute tubulointerstitial nephritis, that can happen at any time during treatment with PPI medicines including lansoprazole delayed-release capsules A type of kidney problem (acute interstitial nephritis) Some people who take proton pump inhibitor (PPI) medicines, including pantoprazole sodium delayed-release tablets may develop a kidney problem called acute interstitial nephritis that can happen at any time during treatment with pantoprazole sodium delayed-release tablets.

PPIs and CKD: Proton pump inhibitors (PPIs) like lansoprazole and pantoprazole may cause a type of kidney problem called acute interstitial nephritis or acute tubulointerstitial nephritis.

• This kidney problem can happen at any time during treatment with PPI medicines.
• Patients should call their doctor right away if they have a decrease in the amount that they urinate or if they have blood in their urine 2 3. Key points:
• PPIs may increase the risk of kidney problems.
• Patients should be monitored for signs of kidney problems.
• The exact relationship between PPIs and chronic kidney disease (CKD) is not explicitly stated in the provided drug labels.

From the Research

Association between PPIs and CKD

• The use of proton pump inhibitors (PPIs) has been linked to an increased risk of chronic kidney disease (CKD) in several studies 4, 5, 6, 7, 8.
• A systematic review and meta-analysis found that PPI use was significantly associated with an increased risk of CKD (RR 1.72,95% CI: 1.02-2.87, p = 0.03) 5.
• Another study found that CKD patients are exposed to more PPIs compared to non-CKD patients, and that PPI use is associated with incident CKD, CKD progression, and end-stage renal disease 6.

Mechanisms and Risk Factors

• The exact mechanisms by which PPIs contribute to CKD are not fully understood, but it is thought that PPIs may induce acute interstitial nephritis (AIN), which can lead to CKD 7.
• Residual confounding and bias related to study design may have contributed to the controversy surrounding PPI safety 7.
• Patients with CKD are at higher risk of developing adverse renal effects from PPI use, and physicians should exercise caution when prescribing PPIs to these patients 6, 7.

Clinical Implications

• The use of PPIs should be carefully considered in patients with CKD, and alternative treatments should be explored when possible 4, 5, 7.
• Deprescribing initiatives and healthcare provider education may be necessary to reduce the risk of CKD associated with PPI use 8.
• Further research is needed to fully understand the relationship between PPI use and CKD, and to develop strategies for minimizing the risks associated with PPI use in patients with CKD 5, 7.