ArticleKidney international2014
Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.
Article in Kidney international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
98 citing papers in PubMed, 240 citations in OpenAlex.
- Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV.Kidney international · 2024Trial
- Evaluation of OCT2-mediated drug-drug interactions between ulotaront and metformin in subjects with schizophrenia.Pharmacology research & perspectives · 2024Trial
- Bioequivalence and Food Effect Assessment of 2 Fixed-Dose Combination Formulations of Dolutegravir and Lamivudine.Clinical pharmacology in drug development · 2020Trial
- Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial.International journal of antimicrobial agents · 2017Trial
- Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.Clinical pharmacology and therapeutics · 2016Trial
- The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin.Clinical pharmacokinetics · 2016Trial
- Telaprevir and ribavirin interaction: higher ribavirin levels are not only due to renal dysfunction during triple therapy.Antimicrobial agents and chemotherapy · 2015Trial
- N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction.European journal of clinical pharmacology · 2015Trial
- Overview of pseudo-acute kidney injury.Renal failure · 2026Review
- Superior Efficacy of Tenofovir Alafenamide Compared With Entecavir in Reducing Hepatitis B Surface Antigen: A Multicentre Propensity Score-Matched Study Using Linear Mixed-Effects Models.Alimentary pharmacology & therapeutics · 2026Article
- Extent and Incidence of Pseudo-Worsening of Kidney Function Due to Oral Antitumor Therapeutics in the AMBORA Cohort: An Analysis of Real-World Data.Clinical pharmacology and therapeutics · 2026Article
- Predicting OCT2/MATEs-Mediated Drug Interactions in Healthy Volunteers and Patients with Chronic Kidney Disease: Insights from Extended Clearance Concept, Endogenous Biomarkers, and In Vitro Inhibition Studies (Perspectives from the International Transporter Consortium).Clinical pharmacology and therapeutics · 2025Review
- In Vitro and In Silico Evaluation of the Anti-Aging Potential ofMolecules (Basel, Switzerland) · 2025Article
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- Stopping bosutinib reverses bosutinib-induced elevation of serum creatinine in patients with chronic myeloid leukemia.International journal of hematology · 2025Article
- Comprehensive management of MET tyrosine kinase inhibitor-induced peripheral edema in patients withTranslational lung cancer research · 2025Review
- Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.Precision clinical medicine · 2025Review
- Effects of Cimetidine and Dolutegravir on the Endogenous Drug-Drug Interaction Biomarkers for Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Protein 1 in Healthy Volunteers.Clinical pharmacology and therapeutics · 2025Article
- Transcriptional response to combination antiretroviral therapy predicts side effects and novel targets.Frontiers in pharmacology · 2025Article
- Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury.Advanced pharmaceutical bulletin · 2024Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.