Evidence map›Paper›PMID 28694431›Full record

ArticleScientific reports2017

Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes.

Wei Wu, Kevin T Bush, Sanjay K Nigam

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05105009 (Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function), which is not on this map. Cited by 132 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 2% of its field
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.

NCT05105009 phase1completednot on this mapstarted 2020, after this paper: background citation

Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function: is It Better Than GFR?

TypeinterventionalSponsorInstituto Nacional de Cardiologia Ignacio ChavezRan2020 to 2024Enrolled50ConditionsChronic Kidney FailureArmsFurosemide Injection, Creatinine Powder, Iohexol
3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.

  1. Uremic Toxins in Organ Crosstalk.Frontiers in medicine · 2021
    Pooled it
  2. Article
  3. Review
  4. Pharmaceutics · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. ACS pharmacology & translational science · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Article

72 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Wei WuDepartment of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Kevin T BushDepartment of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Sanjay K NigamDepartment of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA. snigam@ucsd.edu.
University of California, San Diego · US

Funding

The Role of OAT1 in UremiaR01DK109392 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2017 to 2025
$3.8M
Safety and Dose Optimization of High-Dose Anakinra in Kawasaki DiseaseU54HD090259 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2016 to 2018
$2.2M
Safety and Dose Optimization of High-Dose Anakinra in Kawasaki DiseaseP50HD090259 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2019 to 2020
$1.4M
NICHD NIH HHS P50 HD090259NICHD NIH HHS U54 HD090259NIDDK NIH HHS R01 DK109392
6 · The paper itself

Abstract

In vitro data indicates that the kidney proximal tubule (PT) transporters of uremic toxins and solutes (e.g., indoxyl sulfate, p-cresol sulfate, kynurenine, creatinine, urate) include two "drug" transporters of the organic anion transporter (OAT) family: OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Here, we have examined new and prior metabolomics data from the Oat1KO and Oat3KO, as well as newly obtained metabolomics data from a "chemical double" knockout (Oat3KO plus probenecid). This gives a picture of the in vivo roles of OAT1 and OAT3 in the regulation of the uremic solutes and supports the centrality of these "drug" transporters in independently and synergistically regulating uremic metabolism. We demonstrate a key in vivo role for OAT1 and/or OAT3 in the handling of over 35 uremic toxins and solutes, including those derived from the gut microbiome (e.g., CMPF, phenylsulfate, indole-3-acetic acid). Although it is not clear whether trimethylamine-N-oxide (TMAO) is directly transported, the Oat3KO had elevated plasma levels of TMAO, which is associated with cardiovascular morbidity in chronic kidney disease (CKD). As described in the Remote Sensing and Signaling (RSS) Hypothesis, many of these molecules are involved in interorgan and interorganismal communication, suggesting that uremia is, at least in part, a disorder of RSS.

Indexed as

AnimalsBiomarkersGene Knockdown TechniquesKidney Tubules, ProximalMetabolomeMetabolomicsMiceOrganic Anion TransportersOrganic Anion Transport Protein 1Renal Insufficiency, ChronicToxins, BiologicalUremiaBiomarkersOrganic Anion TransportersOrganic Anion Transport Protein 1Toxins, Biologicaluremia middle molecule toxins

Identifiers

PMID28694431
PMCPMC5504054
OpenAlexW2730312060

What OpenQuestion holds

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LicenceCC BY
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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.