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. 2023 Apr 7;15(4):276.
doi: 10.3390/toxins15040276.

Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients with Chronic Kidney Disease

Carolla El Chamieh  1 , Islam Amine Larabi  2   3 , Solène M Laville  4   5 , Christian Jacquelinet  1   6 , Christian Combe  7   8 , Denis Fouque  9   10 , Maurice Laville  10 , Luc Frimat  11   12 , Roberto Pecoits-Filho  13   14 , Céline Lange  1 , Bénédicte Stengel  1 , Natalia Alencar De Pinho  1 , Jean-Claude Alvarez  2   3 , Ziad A Massy  1   15 , Sophie Liabeuf  4   5 ; Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group
Affiliations

Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients with Chronic Kidney Disease

Carolla El Chamieh et al. Toxins (Basel). .

Abstract

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m2), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, 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 UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies.

Trial registration: ClinicalTrials.gov NCT03381950.

Keywords: chronic kidney disease; indoxyl sulfate; proton-pump inhibitor; uremic toxins.

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Conflict of interest statement

C.E.C., I.A.L., S.M.L., C.J., C.C., D.F., M.L., L.F., R.P.-F, C.L., N.A.D.P., J.-C.A. and S.L., declare no conflict of interest. B.S. coordinates the CKD-REIN cohort study, funded by the Agence Nationale de la Recherche through the 2010 “Cohortes-Investissements d’Avenir” program and by the 2010 national Programme Hospitalier de Recherche Clinique. CKD-REIN has also been supported through a public–private partnership with Amgen, Fresenius Medical Care, and GlaxoSmithKline (GSK), since 2012, Lilly France since 2013, Otsuka Pharmaceutical since 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Sanofi-Genzyme from 2012 to 2015, and Vifor Fresenius and AstraZeneca since 2018. INSERM Transfert set up and has managed this partnership since 2011. Z.A.M. reports having received grants for CKD-REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp & Dohme-Chibret, Sanofi-Genzyme, Lilly, Otsuka, AstraZeneca, Vifor and the French government, as well as fees and grants to charities from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. The sponsors had no role in the design, execution, interpretation, or writing of the study.

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