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

Autor: El Chamieh C; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, 94807 Villejuif, France., Larabi IA; Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, 92380 Garches, France.; UVSQ, Université Paris-Saclay, Inserm U1018, CESP, Équipe MOODS, MasSpecLab, 78180 Montigny-le-Bretonneux, France., Laville SM; Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, 80054 Amiens, France.; MP3CV Laboratory, Jules Verne University of Picardie, F-80054 Amiens, France., Jacquelinet C; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, 94807 Villejuif, France.; Biomedecine Agency, 93210 Saint Denis La Plaine, France., Combe C; Service de Néphrologie Transplantation Dialyse Aphérèse, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux, France.; INSERM, U1026, Univ. Bordeaux, 33076 Bordeaux, France., Fouque D; Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, 69495 Pierre-Bénite, France.; Université de Lyon, CarMeN INSERM 1060, 69008 Lyon, France., Laville M; Université de Lyon, CarMeN INSERM 1060, 69008 Lyon, France., Frimat L; Nephrology Department, CHRU de Nancy, 54000 Vandoeuvre-lès-Nancy, France.; Lorraine University, APEMAC, 54000 Vandoeuvre-lès-Nancy, France., Pecoits-Filho R; Arbor Research Collaborative for Health, Ann Arbor, MI 48108, USA.; School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba 80215-901, Brazil., Lange C; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, 94807 Villejuif, France., Stengel B; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, 94807 Villejuif, France., Alencar De Pinho N; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, 94807 Villejuif, France., Alvarez JC; Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, 92380 Garches, France.; UVSQ, Université Paris-Saclay, Inserm U1018, CESP, Équipe MOODS, MasSpecLab, 78180 Montigny-le-Bretonneux, France., Massy ZA; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, 94807 Villejuif, France.; Department of Nephrology, Ambroise Paré University Hospital, APHP, 92104 Boulogne-Billancourt, France., Liabeuf S; Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, 80054 Amiens, France.; MP3CV Laboratory, Jules Verne University of Picardie, F-80054 Amiens, France.
Jazyk: angličtina
Zdroj: Toxins [Toxins (Basel)] 2023 Apr 07; Vol. 15 (4). Date of Electronic Publication: 2023 Apr 07.
DOI: 10.3390/toxins15040276
Abstrakt: 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 m 2 ) 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 m 2 ), 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.
Databáze: MEDLINE
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