Proton Pump Inhibitors May Speed Up Kidney Disease Progression in Pre-ESRD Patients: Study

"Our study highlights the heightened renal risk, particularly for patients with moderate to advanced CKD, when prescribing PPIs, emphasizing the need for careful consideration by clinicians managing pre-ESRD patients with PPIs and H2 blockers (H2Bs)," the researchers wrote in BMC Nephrology.

Although proton pump inhibitors are widely prescribed for gastrointestinal (GI) diseases, numerous studies have raised concerns about their potential adverse effects on kidney health. Most existing evidence has focused on evaluating the risks associated with PPI use in individuals with normal renal function, with limited data on their impact in patients with moderate to advanced chronic kidney disease. Ching-Lan Cheng, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan, and colleagues address this gap by examining the accelerated decline in renal function associated with PPI use and the heightened risk of acute kidney injury (AKI) in pre-end-stage renal disease patients.

For this purpose, the researchers conducted a retrospective cohort study, including adult patients with CKD stages 3b to 5 who initiated PPI or H2 blocker (H2B) therapy between 2011 and 2018. To evaluate the risk of renal events, they utilized the Cox proportional hazard model to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Additionally, sensitivity analyses were performed, incorporating propensity score matching, as-treated analysis, and subgroup analysis to ensure the robustness of the findings.

The following were the key findings of the study:

• The study analyzed a cohort of 83,432 pre-ESRD patients, including 5,138 treated with H2 blockers (H2B) and 1,051 with proton pump inhibitors (PPIs).
• Patients using PPIs had a significantly higher likelihood of progressing to ESRD compared to those on H2B (adjusted HR: 1.495).
• Omeprazole use was associated with an increased risk of ESRD and AKI (adjusted HR: 1.784).
• Esomeprazole use also showed a significantly higher risk of ESRD and AKI (adjusted HR: 1.847).

The study conducted in Taiwan highlights a significant association between PPI use and an increased risk of accelerated progression to ESRD and AKI in pre-ESRD patients compared to H2 blockers.

"These findings demonstrate a more pronounced renal risk than previous cohort studies, particularly in this vulnerable population. Subgroup analyses further revealed that PPIs like omeprazole and esomeprazole, which have auto-inhibition effects on CYP2C19, were linked to higher hazard ratios for ESRD development than other PPIs," the researchers wrote.

"Given Taiwan’s distinction as having the highest global incidence of ESRD, we emphasize the need for a more personalized approach to PPI use in pre-ESRD patients. This includes reconsidering prescription practices, especially for those in the late stages of CKD, and promoting de-prescription strategies to enhance renal safety," they concluded.

Reference:

Huang, CH., Tsai, CJ., Su, CC. et al. Accelerated risk of renal disease progression in pre-ESRD patients with proton pump inhibitors use: a nationwide population-based study. BMC Nephrol 25, 469 (2024). https://doi.org/10.1186/s12882-024-03867-6