Long-term PPI use was significantly associated with higher serum indoxyl sulfate concentrations in Japanese CKD patients, with multiple regression analysis linking PPI prescription and lower eGFR to elevated serum IS levels.
Key Findings
Results
Serum indoxyl sulfate concentrations were significantly higher in patients receiving long-term PPI prescriptions compared to non-PPI patients.
PPI group median serum IS: 15.37 (IQR 9.69–19.80) µM
Non-PPI group median serum IS: 10.66 (IQR 6.97–14.19) µM
Difference was statistically significant at p = 0.03
Serum IS was measured by HPLC
Results
Multiple regression analysis identified PPI prescription and lower eGFR as independent predictors of higher serum indoxyl sulfate levels.
Both PPI use and lower eGFR were linked to higher serum IS in multiple regression analysis
The study design was single-center and cross-sectional
The analysis included 29 patients in the PPI group and 28 in the non-PPI group
Methods
The study population consisted of Japanese CKD patients with moderately to severely reduced kidney function.
Patients had an estimated glomerular filtration rate (eGFR) of 15 to 44 mL/min/1.73 m²
Patients attended outpatient visits at a nephrology and/or diabetes department
The study period was between October 2022 and December 2023
Total analyzed sample: 57 patients (29 PPI group, 28 non-PPI group)
Background
PPIs are implicated in CKD progression potentially through inhibition of organic anion transporters and effects on intestinal microbiota, which may influence indoxyl sulfate levels.
PPIs are known to inhibit organic anion transporters (OATs)
PPIs are known to affect intestinal microbiota
Indoxyl sulfate is described as a uremic toxin that contributes to CKD progression
The mechanism behind PPI-related CKD progression was described as unclear prior to this study
Conclusions
The authors concluded that more detailed studies are required to evaluate the contribution of intestinal microbiota and diet to the observed association between PPI use and elevated indoxyl sulfate.
The study highlights 'an apparent association of long-term prescriptions of PPIs with high serum IS concentrations'
The authors called for studies evaluating contributions of intestinal microbiota and diet
The study was limited by its cross-sectional, single-center design
Kawamoto K, Kadomura S, Nabeki M, Sasaki H, Yamada K, Noda M, et al.. (2026). Long-Term Use of Proton Pump Inhibitors Affects Blood Levels of Indoxyl Sulfate in Japanese Patients with Chronic Kidney Disease.. Biological & pharmaceutical bulletin. https://doi.org/10.1248/bpb.b25-00465