Long-Term Use of Proton Pump Inhibitors Affects Blood Levels of Indoxyl Sulfate in Japanese Patients with Chronic Kidney Disease

Abstract

Proton pump inhibitors (PPIs) are implicated in the progression of chronic kidney disease (CKD), but the mechanism behind this is unclear. PPIs are known to inhibit organic anion transporters (OATs) and affect intestinal microbiota. PPI use may influence serum concentrations of indoxyl sulfate (IS), a uremic toxin that contributes to CKD. This study compares serum IS concentrations between Japanese patients receiving long-term PPI prescriptions and those receiving non-PPIs, evaluating the effect of long-term PPI therapies on serum IS concentrations. This single-center, cross-sectional study included patients with an estimated glomerular filtration rate (eGFR) of 15 to 44 mL/min/1.73 m,² who attended an outpatient visit at a nephrology and/or diabetes department between October 2022 and December 2023. Serum IS concentrations were measured by HPLC. The analysis included 29 patients in the PPI group and 28 in the non-PPI group; serum IS concentrations were significantly higher in the PPI group [median (interquartile range) 15.37 (9.69–19.80) µM] and non-PPI group [median (interquartile range) 10.66 (6.97–14.19) µM], p = 0.03. Multiple regression analysis was performed, linking prescription of PPIs and lower eGFR to higher serum IS levels. This study highlights an apparent association of long-term prescriptions of PPIs with high serum IS concentrations. However, more detailed studies are required to evaluate the contribution of intestinal microbiota and diet to this phenomenon.