P-CABs May Offer Renal Safety Advantage Over PPIs in Patients With CKD

Proton pump inhibitors (PPIs) are among the most widely prescribed medications in the world, and patients with chronic kidney disease (CKD) are particularly heavy users. Because CKD raises the risk of gastrointestinal disorders such as gastroesophageal reflux disease (GERD), and because many patients with CKD require gastroprotection alongside nonsteroidal anti-inflammatory drugs or anticoagulants, PPIs are a routine part of the pharmacologic landscape in this population.

However, accumulating evidence has linked PPIs to accelerated renal function decline, creating a genuine clinical dilemma for pharmacists and prescribers managing patients whose kidneys can least afford additional insult.^1,2

New study findings published in Kidney International Reports offer a potential path forward. Researchers from Jeonbuk National University and Ewha Woman’s University in South Korea used a target trial emulation framework and Korean National Health Insurance data to compare renal outcomes in patients with CKD who initiated potassium-competitive acid blockers (P-CABs) versus PPIs for GERD. Their findings suggest P-CABs—a newer class of acid-suppressive agents—may carry a meaningfully lower risk of kidney function deterioration in this high-risk group.³

A Familiar Drug Class Under Scrutiny

PPIs have long been the standard first-line pharmacologic therapy for GERD, and patients with CKD are prescribed them at disproportionately high rates. Prior research has raised red flags about this pattern. Studies have linked PPI use in patients with CKD to a significantly elevated risk of progression to end-stage kidney disease (ESKD) compared with H2 receptor antagonists. Proposed mechanisms include PPI-induced acute interstitial nephritis and accelerated endothelial cell senescence through impaired lysosomal acidification, a process that may amplify oxidative stress and vascular aging, ultimately contributing to kidney injury.^3,4

P-CABs have emerged as a promising alternative. Unlike PPIs, which require an acidic environment for activation, P-CABs act rapidly and maintain prolonged acid suppression.⁵

Study Design and Patient Population

The researchers drew on Korean National Health Insurance data, a database covering approximately 97% of the country's population, to identify adults aged 20 years or older with established CKD who were newly initiating P-CABs or PPIs for GERD between 2019 and 2022. Patients with a prior history of renal replacement therapy (RRT) or a recent cancer diagnosis were excluded. A total of 34,077 patients were included in the final cohort, with 4107 P-CAB users and 29,970 PPI users identified before propensity score matching.³

The primary outcome was the first initiation of composite RRT, which included hemodialysis, peritoneal dialysis, and kidney transplantation. The investigators employed Cox proportional hazards models and conducted an intention-to-treat analysis as a secondary approach.³

Key Findings: A Significant Risk Reduction

After propensity score matching and covariate adjustment, P-CAB use was associated with a 37% lower risk of composite RRT initiation compared with PPI use (hazard ratio [HR]: 0.63; 95% CI: 0.45–0.88; P = .0070). While HRs for the individual RRT components—hemodialysis, peritoneal dialysis, and kidney transplantation—all trended in favor of P-CABs, those individual comparisons did not reach statistical significance. The intention-to-treat analysis showed a consistent, though slightly attenuated, result (HR: 0.90; 95% CI: 0.82–0.99), which the authors attributed in part to the dilution of exposure-outcome associations over longer follow-up.³

Subgroup analyses revealed that the renal safety advantage of P-CABs was particularly pronounced in certain patient populations. Patients aged 65 years or older showed a significantly lower risk with P-CAB use (adjusted HR: 0.59; 95% CI: 0.36–0.95), as did patients with a history of diabetes (adjusted HR: 0.62; 95% CI: 0.41–0.94) and those with prior use of angiotensin-converting enzyme inhibitors (ACE) or angiotensin II receptor blockers (ARB) (adjusted HR: 0.60; 95% CI: 0.39–0.91). Longer treatment durations of 29 days or more and lower average daily doses were also associated with greater protective effects with P-CABs.³

Clinical Implications for Pharmacy Practice

For pharmacists involved in medication therapy management or transitions of care for patients with CKD, these findings carry practical weight. Patients with CKD are frequently co-prescribed PPIs for gastroprotection alongside nephrotoxic or gastrointestinal-irritating agents, and they often carry additional risk factors—older age, diabetes, and concurrent ACE inhibitor or ARB use—that this study identified as precisely the subgroups where P-CABs showed the most meaningful renal safety signal.^3,4

The authors note that phase 3 clinical trials of P-CABs have historically excluded patients with clinically significant renal disease, making real-world data of this kind especially valuable. To their knowledge, this is the first large-scale cohort study to directly compare RRT risk between P-CABs and PPIs in patients with CKD. The study was conducted exclusively in a South Korean population, where tegoprazan (K-CAB; Sebela Pharmaceuticals) accounted for 93.9% of P-CAB prescriptions, a limitation that warrants caution when extrapolating to other P-CAB agents or broader patient populations. Additionally, the claims-based nature of the data precluded inclusion of laboratory values such as serum creatinine or estimated glomerular filtration rate.³

Nonetheless, the study adds an important evidence-based dimension to the ongoing conversation about PPI safety in renally compromised patients, and positions P-CABs as a drug class pharmacists should be familiar with as availability in the United States expands.³

REFERENCES

1. Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Amer Journ Gastroen. 2022;117(1):27-56. doi:10.14309/ajg.0000000000001538

2. Kim SG, Cho JM, Han K, et al. Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study. BMJ Open. 2024;14(1):e078032. doi:10.1136/bmjopen-2023-078032

3. Kim SY, Lee H, Kim JS, Kim HJ, Jeon HL. Renal outcomes with potassium-competitive acid blockers versus proton pump inhibitors in CKD. KI Reports. 2026;11(6):106524. doi:10.1016/j.ekir.2026.106524

4. Parmar MP, Kaleem S, Samuganathan P, et al. Impact of proton pump inhibitors on kidney function and chronic kidney disease progression: A systematic review. Cureus. 2023;15(12):e49883. doi:10.7759/cureus.49883

5. Inatomi N, Matsukawa J, Sakurai Y, Otake K. Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases. Pharmacology & Therapeutics. 2016;168:12-22. doi:10.1016/j.pharmthera.2016.08.001