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Open AccessArticle

Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion

1
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3854 CG Utrecht, The Netherlands
2
Department of Nephrology and Hypertension, University Medical Center Utrecht, 3582 CX Utrecht, The Netherlands
3
(Bio)artificial Organs, Department of Biomaterials Science and Technology, University of Twente, 7522 LW Enschede, The Netherlands
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(6), 391; https://doi.org/10.3390/toxins12060391
Received: 10 May 2020 / Revised: 5 June 2020 / Accepted: 9 June 2020 / Published: 12 June 2020
(This article belongs to the Section Uremic Toxins)
In chronic kidney disease (CKD), the secretion of uremic toxins is compromised leading to their accumulation in blood, which contributes to uremic complications, in particular cardiovascular disease. Organic anion transporters (OATs) are involved in the tubular secretion of protein-bound uremic toxins (PBUTs). However, OATs also handle a wide range of drugs, including those used for treatment of cardiovascular complications and their interaction with PBUTs is unknown. The aim of this study was to investigate the interaction between commonly prescribed drugs in CKD and endogenous PBUTs with respect to OAT1-mediated uptake. We exposed a unique conditionally immortalized proximal tubule cell line (ciPTEC) equipped with OAT1 to a panel of selected drugs, including angiotensin-converting enzyme inhibitors (ACEIs: captopril, enalaprilate, lisinopril), angiotensin receptor blockers (ARBs: losartan and valsartan), furosemide and statins (pravastatin and simvastatin), and evaluated the drug-interactions using an OAT1-mediated fluorescein assay. We show that selected ARBs and furosemide significantly reduced fluorescein uptake, with the highest potency for ARBs. This was exaggerated in presence of some PBUTs. Selected ACEIs and statins had either no or a slight effect at supratherapeutic concentrations on OAT1-mediated fluorescein uptake. In conclusion, we demonstrate that PBUTs may compete with co-administrated drugs commonly used in CKD management for renal OAT1 mediated secretion, thus potentially compromising the residual renal function. View Full-Text
Keywords: protein-bound uremic toxins; chronic kidney disease management; drug-toxin interaction; OAT1-mediated transport protein-bound uremic toxins; chronic kidney disease management; drug-toxin interaction; OAT1-mediated transport
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Mihaila, S.M.; Faria, J.; Stefens, M.F.J.; Stamatialis, D.; Verhaar, M.C.; Gerritsen, K.G.F.; Masereeuw, R. Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion. Toxins 2020, 12, 391.

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