Evidence map›Paper›PMID 26490509›Full record

ArticleClinical journal of the American Society of Nephrology : CJASN2015

Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters.

Sanjay K Nigam, Wei Wu, Kevin T Bush, Melanie P Hoenig, Roland C Blantz, Vibha Bhatnagar

Abstract read
In one paragraph

Article in Clinical journal of the American Society of Nephrology : CJASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed, 2 pooled it
10.5field-weighted citation impact, top 1% 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.

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

130 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.

  1. Pooled it
  2. Uremic Toxins in Organ Crosstalk.Frontiers in medicine · 2021
    Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Kidney Tubule Secretion and AKI After Cardiac Surgery.Kidney international reports · 2026
    Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Kidney Tubule Secretion Can Discriminate the Cause of Acute Kidney Injury in Cirrhosis.Clinical journal of the American Society of Nephrology : CJASN · 2025
    Article
  18. Article
  19. Article
  20. Article

70 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

6 authors at 3 institutions in 1 country.

Sanjay K NigamDepartment of Medicine, Department of Pediatrics, Department of Cell & Molecular Medicine, snigam@ucsd.edu.
Wei WuDepartment of Medicine.
Kevin T BushDepartment of Pediatrics.
Melanie P HoenigDivision of Nephrology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Roland C BlantzDivision of Nephrology-Hypertension, and Veterans Affairs San Diego Healthcare System, San Diego, California; and.
Vibha BhatnagarDivision of Family & Preventative Medicine, University of California-San Diego, La Jolla, California;
University of California, San Diego · USBeth Israel Deaconess Medical Center · USVA San Diego Healthcare System · US

Funding

TRAINING & OUTREACH COREU54HD071600 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRADLEY, JOHN S · 2011 to 2015
$3.6M
Substrate Specificity of the Choroid Plexus and Kidney Transporter Oat1R01GM098449 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2012 to 2015
$2.1M
Structure Function Analysis of the Multi-specific Drug Transporter OCT1R01GM104098 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2013 to 2016
$1.6M
NICHD NIH HHS U54 HD071600NIGMS NIH HHS GM098449NIGMS NIH HHS GM104098NIGMS NIH HHS R01 GM098449NIGMS NIH HHS R01 GM104098
6 · The paper itself

Abstract

The proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily. We review the basic physiology of these SLC and ABC transporters, many of which are often called drug transporters. With an emphasis on OAT1 (SLC22A6), the closely related OAT3 (SLC22A8), and OCT2 (SLC22A2), we explore the implications of recent in vitro, in vivo, and clinical data pertinent to the kidney. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liver-derived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. These transporters may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD.

Indexed as

Biological TransportHumansKidney Tubules, ProximalOrganic Anion TransportersPharmaceutical PreparationsSignal TransductionUremiaOrganic Anion TransportersPharmaceutical PreparationsAcute Kidney InjuryAnti-Bacterial AgentsATP-Binding Cassette TransportersCationsChronicDiureticsdrug transporternephrotoxicityOrganic Anion TransportersRenal Insufficiencyrenal physiology

Identifiers

PMID26490509
PMCPMC4633783
OpenAlexW1801619426

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.