ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2022
Potential interactions between uraemic toxins and drugs: an application in kidney transplant recipients treated with calcineurin inhibitors.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- Drug-induced hyperuricemia: multi-pathway regulation, causative drugs, and individualized management strategies.Frontiers in pharmacology · 2026Review
- Clinical Pharmacokinetic-Pharmacodynamic Relationships of Pharmacological Strategies for Attenuating p-Cresyl Sulfate in Patients with Kidney Disease.Clinical pharmacokinetics · 2025Article
- Serum Trimethylamine N-Oxide Levels as a Predictor of Peripheral Arterial Disease in Kidney Transplant Recipients.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Impact of High Tacrolimus Exposure on Graft Function and Development of a Prediction Model in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.Drug design, development and therapy · 2025Article
- Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation ofPharmaceutics · 2024Review
- A simple and accurate LC‑MS/MS method for monitoring cyclosporin A that is suitable for high throughput analysis.Experimental and therapeutic medicine · 2023Article
- Significant Correlations between p-Cresol Sulfate and Mycophenolic Acid Plasma Concentrations in Adult Kidney Transplant Recipients.Clinical drug investigation · 2022Observational
- The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction.Toxins · 2022Review
- Article
- Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight.International journal of molecular sciences · 2021Review
- Trimethylamine N-oxide and kidney diseases: what do we know?Jornal brasileiro de nefrologiaReview
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8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe uraemic toxins that accumulate as renal function deteriorates can potentially affect drug pharmacokinetics. This study's objective was to determine whether plasma concentrations of certain uraemic toxins are correlated with blood concentrations of two immunosuppressants.
methodsDRUGTOX was a cross-sectional study of 403 adult patients followed up after kidney transplantation and who had undergone therapeutic drug monitoring (TDM) of calcineurin inhibitors (tacrolimus or cyclosporin) between August 2019 and March 2020. For each patient, immunosuppressant trough concentrations (C0) were measured in whole blood samples and then normalized against the total daily dose (C0:D ratio). The sample was assayed for five uraemic toxins [urea, trimethylamine N-oxide (TMAO), indole acetic acid (IAA), p-cresylsulphate (PCS) and indoxylsulphate (IxS)] using liquid chromatography-tandem mass spectrometry.
resultsThe median age was 56 years [interquartile range (IQR) 48-66] and the median estimated glomerular filtration rate was 41 mL/min/1.73 m2 (IQR 30-57). Age, sex, body mass index (BMI), urea, IxS and PCS were significantly associated with an increment in the tacrolimus C0:D ratio. A multivariate analysis revealed an independent association with IxS [odds ratio 1.36 (95% confidence interval 1.00-1.85)] after adjustment for sex, age and BMI, whereas adjustment for age weakened the association for PCS and urea. In a univariate logistic analysis, age, sex, BMI and the TMAO level (but not PCS, IxS, IAA or urea) were significantly associated with an increment in the cyclosporine C0:D ratio.
conclusionsEven though TDM and dose adaptation of immunosuppressants keep levels within the therapeutic window, increased exposure to tacrolimus (but not cyclosporine) is associated with an accumulation of PCS, IxS and urea.
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