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

被引:2
作者
El Chamieh, Carolla [1 ]
Larabi, Islam Amine [2 ,3 ]
Laville, Solene M. [4 ,5 ]
Jacquelinet, Christian [1 ,6 ]
Combe, Christian [7 ,8 ]
Fouque, Denis [9 ,10 ]
Laville, Maurice [10 ]
Frimat, Luc [11 ,12 ]
Pecoits-Filho, Roberto [13 ,14 ]
Lange, Celine [1 ]
Stengel, Benedicte [1 ]
De Pinho, Natalia Alencar [1 ]
Alvarez, Jean-Claude [2 ,3 ]
Massy, Ziad A. [1 ,15 ]
Liabeuf, Sophie [4 ,5 ]
机构
[1] Univ Versailles St Quentin, Univ Paris Saclay, Ctr Res Epidemiol & Populat Hlth CESP, INSERM UMRS 1018, F-94807 Villejuif, France
[2] Hop Raymond Poincare, AP HP, Dept Pharmacol & Toxicol, F-92380 Garches, France
[3] Univ Paris Saclay, Equipe MOODS, UVSQ, Inserm U1018,MasSpecLab,CESP, F-78180 Montigny Le Bretonneux, France
[4] Amiens Picardie Univ, Dept Clin Pharmacol, Pharmacoepidemiol Unit, Med Ctr, F-80054 Amiens, France
[5] Jules Verne Univ Picardie, MP3CV Lab, F-80054 Amiens, France
[6] Biomed Agcy, F-93210 La Plaine St Denis, France
[7] Ctr Hosp Univ Bordeaux, Serv Nephrol Transplantat Dialyse Apherese, F-33076 Bordeaux, France
[8] Univ Bordeaux, INSERM, U1026, F-33076 Bordeaux, France
[9] Univ Lyon, Ctr Hosp Lyon Sud, Nephrol Dept, Carmen, F-69495 Pierre Benite, France
[10] Univ Lyon, CarMeN INSERM 1060, F-69008 Lyon, France
[11] CHRU Nancy, Nephrol Dept, F-54000 Vandoeuvre Les Nancy, France
[12] Lorraine Univ, APEMAC, F-54000 Vandoeuvre Les Nancy, France
[13] Arbor Res Collaborat Hlth, Ann Arbor, MI 48108 USA
[14] Pontificia Univ Catolica Parana, Sch Med, BR-80215901 Curitiba, Brazil
[15] Ambroise Pare Univ Hosp, APHP, Dept Nephrol, F-92104 Boulogne, France
关键词
uremic toxins; indoxyl sulfate; proton-pump inhibitor; chronic kidney disease; ORGANIC ANION TRANSPORTERS; DRUG-DRUG INTERACTIONS; ELIMINATION; SULFATE;
D O I
10.3390/toxins15040276
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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.
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页数:12
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