PPI Use and Uremic Toxins in Patients With CKD

By Victoria Socha - September 26, 2023

Patients with chronic kidney disease (CKD) are commonly treated with proton-pump inhibitors (PPIs). PPIs and uremic toxins are eliminated by a kidney tubular organic anion transporter system.

Carolla El Chamieh and colleagues conducted analysis designed to examine the association between PPI prescription and serum concentrations of various uremic toxins. Results were reported during the ERA 60th Congress in a presentation titled Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients With Chronic Kidney Disease.

The analysis included a randomly selected subgroup of participants in the CKDREIN prospective cohort with available frozen samples collected at baseline. The CKDREIN cohort included adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2.

The researchers used a validated liquid chromatography tandem mass spectrometry technique to measure serum concentrations of 10 uremic toxins. Using the log uremic toxin concentration as the dependent variable, the researchers conducted multiple linear regression models.

A total of 680 patients were included in the analysis; median age was 68 years, and median eGFR was 32 mL/min/1.73 m2. Thirty-one percent of the cohort had a prescription for a PPI at baseline.

Compared with patients not using a PPI, those in the PPI group had higher levels of certain uremic toxins, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free pcresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. Following adjustment for baseline comorbidities, the number of coprescribed drugs, and laboratory data including eGFR, the associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant.

“Our results indicate that PPI prescription is independently associated with serum uremic toxin retention,” the authors said. “These findings indicate a potential mechanism for side effect of PPIs in CKD patients that will need to be confirmed by longitudinal studies.”

Source: El Chamieh C, Larabi IS, Laville S, et al. Proton-pump inhibitors and serum concentrations of uremic toxins in patients with chronic kidney disease. Presentation #3386. Abstract of a presentation at the European Renal Association 60th Congress; June 15-18, 2023; Milan, Italy.

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