Evidence map›Paper›PMID 40381485›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2025

The impact of progressive chronic kidney disease on hepatic drug metabolism.

Emily D Hartjes, Yong Jin Lim, Thomas J Velenosi, Kait F Al, Jean M Macklaim, Andrew S Kucey, Gregor Reid, Jeremy P Burton, Gregory B Gloor, Bradley L Urquhart

Abstract read
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In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Emily D HartjesDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Yong Jin LimDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Thomas J VelenosiFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Kait F AlDepartment of Microbiology & Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics, London, Ontario, Canada.
Jean M MacklaimDepartment of Microbiology & Immunology, Western University, London, Ontario, Canada.
Andrew S KuceyDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Gregor ReidDepartment of Microbiology & Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics, London, Ontario, Canada.
Jeremy P BurtonDepartment of Microbiology & Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics, London, Ontario, Canada.
Gregory B GloorDepartment of Biochemistry, University of Western Ontario, London, Ontario, Canada.
Bradley L UrquhartDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address: Brad.Urquhart@schulich.uwo.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nonrenal clearance pathways such as drug metabolism are decreased in severe chronic kidney disease (CKD). The impact of progression of CKD on hepatic drug metabolism is unknown. We characterized the effect of progressive CKD on hepatic cytochrome P450 expression and evaluated dysbiosis and uremia as kidney function declined. Rats fed control or CKD-inducing adenine diet were studied at 5 time points over 42 days. Cytochrome P450 expression and activity were compared with alterations in the (1) plasma and liver metabolome and (2) gut bacterial microbiota. CYP3A2 and CYP2C11 were downregulated in CKD by ≥76% (P < .001) concurrently with or slightly prior to CKD onset as defined by serum creatinine. Metabolite profiles were altered prior to changes in the gut microbiota, and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate, and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11 expression. Bacterial genera Turicibacter and Parabacteroides were identified as being characteristic of CKD. In conclusion, CYP3A2 and CYP2C11 are downregulated before dysbiosis and uremia. SIGNIFICANCE STATEMENT: This study describes the effect of progressive kidney disease on hepatic CYP2C11 and CYP3A2 enzyme expression and activity in a rat model of CKD. Expression and activity of drug metabolizing enzymes occurs prior to uremia or dysbiosis.

Indexed as

LiverRenal Insufficiency, ChronicAdenineAnimalsAryl Hydrocarbon HydroxylasesCytochrome P-450 Enzyme SystemCytochrome P450 Family 2Disease ProgressionDysbiosisGastrointestinal MicrobiomeMaleMetabolomeRatsRats, Sprague-DawleySteroid 16-alpha-HydroxylaseUremiaAdenineAryl Hydrocarbon HydroxylasesCYP2C11 protein, ratCytochrome P-450 Enzyme SystemCytochrome P450 Family 2Steroid 16-alpha-HydroxylaseUremic ToxinsChronic kidney diseaseDrug metabolismGut microbiomeMetabolomics

Identifiers

PMID40381485
PMCPMC12264556

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Registered trials

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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.