ArticleToxins2013
Effects of decreased vitamin D and accumulated uremic toxin on human CYP3A4 activity in patients with end-stage renal disease.
Article in Toxins, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Effect of End-Stage Kidney Disease Factor on the Sedative Effects of Ciprofol.Drug design, development and therapy · 2026Article
- Gut microbiota in chronic kidney disease-mineral and bone disorder: shared mechanisms, disease-specific signatures, and therapeutic prospects.Frontiers in endocrinology · 2026Review
- Dietary Modulation of CYP3A4 and Its Impact on Statins and Antidiabetic Drugs: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dual effects of indoxyl sulfate on modulation of human hepatic CYP3A activity, with individual differences.PloS one · 2025Article
- The Potential Influence of Uremic Toxins on the Homeostasis of Bones and Muscles in Chronic Kidney Disease.Biomedicines · 2023Review
- The Impact of Suboptimal 25-Hydroxyvitamin D Levels and Cholecalciferol Replacement on the Pharmacokinetics of Oral Midazolam in Control Subjects and Patients With Chronic Kidney Disease.Journal of clinical pharmacology · 2022Article
- Development of an in silico prediction system of human renal excretion and clearance from chemical structure information incorporating fraction unbound in plasma as a descriptor.Scientific reports · 2019Article
- Role of vitamin D receptor in the regulation ofActa pharmaceutica Sinica. B · 2019Review
- Article
- Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.Expert review of clinical pharmacology · 2018Review
- The use of vitamin D analogs is independently associated with the favorable renal prognosis in chronic kidney disease stages 4-5: the CKD-ROUTE study.Clinical and experimental nephrology · 2017Observational
- Identification of potential candidate genes for hypertensive nephropathy based on gene expression profile.BMC nephrology · 2016Article
- Metabolomics analysis of serum 25-hydroxy-vitamin D in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.International journal of epidemiology · 2016Article
- Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5.Clinical pharmacology and therapeutics · 2016Article
- Consequences of renal failure on non-renal clearance of drugs.Clinical pharmacokinetics · 2014Review
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
In patients with end-stage renal disease, not only renal clearance but also hepatic clearance is known to be impaired. For instance, the concentration of erythromycin, a substrate of cytochrome P450 3A4 (CYP3A4), has been reported to be elevated in patients with end-stage renal disease. The purpose of this study is to elucidate the reason for the decrease in hepatic clearance in patients with end-stage renal disease. Deproteinized pooled sera were used to assess the effects of low-molecular-weight uremic toxins on CYP3A4 activity in human liver microsomes and human LS180 cells. Four uremic toxins (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) present at high concentrations in uremic serum were also studied. Simultaneous treatment of uremic serum (less than 10%) or uremic toxins did not affect testosterone 6β-hydroxylation in human liver microsomes. On the other hand, pretreatment of each serum activates CYP3A4 in LS180 cells, and the increased CYP3A4 activity in uremic serum-treated cells was smaller than normal serum-treated cells. In addition, CYP3A4 and CYP24A1 mRNA levels also increased in LS180 cells exposed to normal serum, and this effect was reduced in uremic serum-treated cells and in cells exposed to uremic serum added to normal serum. Furthermore, addition of 1,25-dihydroxyvitamin D to uremic serum partially restored the serum effect on CYP3A4 expression. The present study suggests that the decrease of 1,25-dihydroxyvitamin D and the accumulation of uremic toxins contributed to the decreased hepatic clearance of CYP3A4 substrates in patients with end-stage renal disease.
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Registered trials
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