Two rapid, accurate liquid chromatography tandem mass spectrometry methods for the quantification of seven uremic toxins: An application for describing their accumulation kinetic profile in a context of acute kidney injury

André, Camille; Bennis, Youssef; Titeca-Beauport, Dimitri; Caillard, P.; Cluet, Yan; Kamel, Saı̈d; Choukroun, Gabriel; Maizel, Julien; Liabeuf, Sophie; Bodeau, Sandra

doi:10.1016/j.jchromb.2020.122234

Cited by 21 publications

(34 citation statements)

References 34 publications

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“…Plasma levels of IxS, pCS, IAA and TMAO were assayed using a liquid chromatography (Shimadzu, Marne-la-Vallée, France)-tandem mass spectrometry (3200 QTRAP™, Sciex, Les Ulis, France) technique [58]. Briefly, UTs were extracted from 50 µL of plasma by adding 200 µL of an ice-cold acetonitrile solution containing a mix of deuterated internal standards.…”

Section: Uremic Toxin Assaysmentioning

confidence: 99%

The Prescription of Drugs That Inhibit Organic Anion Transporters 1 or 3 Is Associated with the Plasma Accumulation of Uremic Toxins in Kidney Transplant Recipients

André

Mernissi

Choukroun

et al. 2021

Toxins

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The renal elimination of uremic toxins (UTs) can be potentially altered by drugs that inhibit organic anion transporters 1/3 (OAT1/OAT3). The objective of the present study was to determine whether the prescription of at least one OAT1/OAT3 inhibitor was associated with the plasma accumulation of certain UTs in kidney transplant recipients. We included 403 kidney transplant recipients. For each patient, we recorded all prescription drugs known to inhibit OAT1/OAT3. Plasma levels of four UTs (trimethylamine N-oxide (TMAO), indole acetic acid (IAA), para-cresylsulfate (pCS), and indoxylsulfate (IxS) were assayed using liquid chromatography-tandem mass spectrometry. Plasma UT levels were significantly higher among patients prescribed at least one OAT inhibitor (n = 311) than among patients not prescribed any OAT inhibitors (n = 92). Multivariate analysis revealed that after adjustment for age, estimated glomerular filtration rate (eGFR), plasma level of albumin and time since transplantation, prescription of an OAT1/OAT3 inhibitor was independently associated with the plasma accumulation of pCS (adjusted odds ratio (95% confidence interval): 2.11 (1.26; 3.61]). Our results emphasize the importance of understanding the interactions between drugs and UTs and those involving UT transporters in particular.

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Section: Uremic Toxin Assaysmentioning

confidence: 99%

The Prescription of Drugs That Inhibit Organic Anion Transporters 1 or 3 Is Associated with the Plasma Accumulation of Uremic Toxins in Kidney Transplant Recipients

André

Mernissi

Choukroun

et al. 2021

Toxins

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“…Therefore, quantitative assessment of the accumulation of indoxyl sulfate and CMPF may help predict the activities of drug-metabolizing enzymes and drug transporters in individual patients and contribute to optimizing the dosage of the substrate drugs. Assays for simultaneous quantification of indoxyl sulfate and CMPF concentrations in human serum using LC-MS/MS have been reported [21][22][23][24][25]. However, these methods have some weaknesses.…”

Section: Introductionmentioning

confidence: 99%

“…The calibration ranges may not be adequately wide to cover all the indoxyl sulfate and CMPF concentrations in human plasma. Samples pretreated by deproteinization method [21][22][23][24][25] may contain abundant residues from the plasma matrix, and pretreatment by ultrafiltration method [24] has a risk of non-specific absorption of solute to the ultrafiltration membrane. Furthermore, 50-160 μL of serum is used for measurement [22][23][24][25], and reducing the volume of blood sample required for measurement would facilitate measurements in pediatric, older, and critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

Highly sensitive simultaneous quantification of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid in human plasma using ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry

Oda

Suzuki

Sato

et al. 2022

J of Separation Science

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Indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid are uremic toxins that accumulate in renal failure and have been reported to decrease the activities of the drug‐metabolizing enzyme cytochrome P450 3A and the drug transporter organic anion transporting polypeptides 1B, respectively. In this study, we established and validated an assay for simultaneous quantification of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid in human plasma. The samples were pretreated by solid‐phase extraction, and measured by ultra‐high‐performance liquid chromatography–tandem mass spectrometry. The validation results for this assay were within the acceptable limits recommended by the US Food and Drug Administration, with a lower limit of quantitation of 0.05 μg/mL for both indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid. Recovery rates of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid corrected by internal standard were 100.7–101.9 and 100.2–101.3%, respectively. Matrix effects of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid corrected by internal standard were 101.1–105.5 and 97.0–103.8%, respectively. The validated assay was used to analyze indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid concentrations in the plasma samples of healthy volunteers and patients with chronic kidney disease. All the measured plasma indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid concentrations were within the calibration ranges. This novel method may contribute to predicting the activities of drug‐metabolizing enzymes and drug transporters in individual patients.

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“…Blood levels of UTs (CMPF, HA, IAA, IS, pCS, pCG, and TMAO) were determined by liquid chromatography (Shimadzu, Marne-la-Vallée, France) coupled to a tandem mass spectrometer (3200 QTRAP, Sciex, Les Ulis, France) [ 64 ]. Briefly, UTs were extracted from 50 µL of serum by adding 200 µL of an ice-cold acetonitrile solution containing the internal standards (d5-CMPF, (13C6)-1H-IAA, (13C6)-IxS, d4-pCS, and d9-TMAO) at a concentration of 500 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

Association between Uremic Toxin Concentrations and Bone Mineral Density after Kidney Transplantation

Batteux

Bodeau

André

et al. 2020

Toxins

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Although uremic osteoporosis is a component of mineral and bone disorder in chronic kidney disease, uremic toxin (UT) concentrations in patients with end-stage kidney disease and bone mineral density (BMD) changes after kidney transplantation have not previously been described. We hypothesized that elevated UT concentrations at the time of transplantation could have a negative impact on bone during the early post-transplantation period. Hence, we sought to determine whether concentrations of UTs (trimethylamine-N-oxide, indoxylsulfate, p-cresylsulfate, p-cresylglucuronide, indole-3-acetic acid, hippuric acid, and 3-carboxy-4-methyl-5-propyl-furanpropionic acid) upon transplantation are predictive markers for (i) osteoporosis one month after transplantation, and (ii) a BMD decrease and the occurrence of fractures 12 and 24 months after kidney transplantation. Between 2012 and 2018, 310 kidney transplant recipients were included, and dual-energy X-ray absorptiometry was performed 1, 12, and 24 months after transplantation. The UT concentrations upon transplantation were determined by reverse-phase high-performance liquid chromatography. Indoxylsulfate concentrations upon transplantation were positively correlated with BMD one month after transplantation for the femoral neck but were not associated with osteoporosis status upon transplantation. Concentrations of the other UTs upon transplantation were not associated with osteoporosis or BMD one month after transplantation. None of the UT concentrations were associated with BMD changes and the occurrence of osteoporotic fractures 12 and 24 months after transplantation. Hence, UT concentrations at the time of kidney transplantation were not predictive markers of osteoporosis or fractures.

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Two rapid, accurate liquid chromatography tandem mass spectrometry methods for the quantification of seven uremic toxins: An application for describing their accumulation kinetic profile in a context of acute kidney injury

Cited by 21 publications

References 34 publications

The Prescription of Drugs That Inhibit Organic Anion Transporters 1 or 3 Is Associated with the Plasma Accumulation of Uremic Toxins in Kidney Transplant Recipients

The Prescription of Drugs That Inhibit Organic Anion Transporters 1 or 3 Is Associated with the Plasma Accumulation of Uremic Toxins in Kidney Transplant Recipients

Highly sensitive simultaneous quantification of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid in human plasma using ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry

Association between Uremic Toxin Concentrations and Bone Mineral Density after Kidney Transplantation

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