Abstract: TH-PO0831
Pantoprazole-Associated Increases in Plasma Creatinine Are Due to Inhibition of Tubular Secretion and Not Kidney Injury
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Karel, Isaac Z., The Ohio State University, Columbus, Ohio, United States
- Pabla, Navjot, The Ohio State University, Columbus, Ohio, United States
Background
Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders and have been associated with reduced estimated glomerular filtration rate (eGFR), acute kidney injury (AKI), and chronic kidney disease in some patient populations. However, the mechanisms underlying these kidney-related effects remain poorly defined. Because serum creatinine is influenced not only by glomerular filtration but also by proximal tubular secretion, we investigated whether pantoprazole increases serum creatinine through inhibition of organic cation transporter 2 (OCT2)-mediated creatinine secretion independent of structural kidney injury.
Methods
Male CD-1 mice received pantoprazole (1, 10, or 100 mg/kg) by oral gavage for seven days under exposure conditions designed to approximate human pharmacologic concentrations. Cisplatin-treated mice served as positive controls for tubular injury. Serum creatinine, transdermal GFR (tGFR), cystatin C, blood urea nitrogen (BUN), kidney injury markers, and histology were evaluated. Human proximal tubular HK-2 cells were used to assess direct cytotoxicity, and transporter assays were performed to determine OCT2 inhibition.
Results
Pantoprazole caused dose-dependent increases in serum creatinine without changes in tGFR, cystatin C, or BUN. Kidney NGAL expression and histology showed no evidence of tubular injury or inflammation. In contrast, cisplatin caused severe tubular injury with reduced tGFR and elevated injury markers. Pantoprazole did not reduce HK-2 cell viability, indicating lack of direct tubular toxicity. Transporter assays demonstrated OCT2 inhibition within clinically relevant concentration ranges. Serum creatinine elevations were rapidly reversible following drug withdrawal.
Conclusion
Pantoprazole elevates serum creatinine through inhibition of OCT2-dependent tubular creatinine secretion independent of reduced glomerular filtration or structural kidney injury. These findings provide a mechanistic explanation for mild and reversible eGFR declines observed during PPI therapy and highlight the importance of distinguishing transporter-mediated changes in creatinine handling from true nephrotoxicity.
Funding
- NIDDK Support