Evidence map›Paper›PMID 27274832›Full record

ArticleClinical kidney journal2016

Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling.

Vibha Bhatnagar, Erin L Richard, Wei Wu, Caroline M Nievergelt, Michael S Lipkowitz, Janina Jeff, Adam X Maihofer, Sanjay K Nigam

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical kidney journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 3 pooled it
8.5field-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.

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

73 citing papers in PubMed, 3 syntheses or guidelines pooled it, 107 citations in OpenAlex.

  1. Pooled it
  2. Uremic Toxins in Organ Crosstalk.Frontiers in medicine · 2021
    Pooled it
  3. Pooled it
  4. Review
  5. Article
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  8. Review
  9. Article
  10. A guide to uraemic toxicity.Nature reviews. Nephrology · 2026
    Review
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13 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

8 authors at 3 institutions in 1 country.

Vibha BhatnagarDepartment of Family Medicine and Public Health , School of Medicine, University of California San Diego , La Jolla, CA , USA.
Erin L RichardDepartment of Family Medicine and Public Health , School of Medicine, University of California San Diego , La Jolla, CA , USA.
Wei WuDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA; Department of Medicine (Nephrology), University of California San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Caroline M NievergeltDepartment of Psychiatry , School of Medicine, University of California San Diego , La Jolla, CA , USA.
Michael S LipkowitzDivision of Nephrology and Hypertension , Georgetown University Medical Center , Washington, DC , USA.
Janina JeffThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai , New York, NY , USA.
Adam X MaihoferDepartment of Psychiatry , School of Medicine, University of California San Diego , La Jolla, CA , USA.
Sanjay K NigamDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA; Department of Medicine (Nephrology), University of California San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
University of California, San Diego · USGeorgetown University Medical Center · USIcahn School of Medicine at Mount Sinai · US

Funding

UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AGARWAL, ANUPAM · 2008 to 2022
$18.3M
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
NIDDK NIH HHS P30 DK079337NIGMS NIH HHS R01 GM098449NIGMS NIH HHS R01 GM104098
6 · The paper itself

Abstract

backgroundIn the setting of chronic kidney disease (CKD), altered extra-renal urate handling may be necessary to regulate plasma uric acid. The Remote Sensing and Signaling Hypothesis (Nigam S. What do drug transporters really do? Nat Rev Drug Discov 2015; 14: 29-44) suggests that multispecific solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters in different tissues are part of an inter-organ communication system that maintains levels of urate and other metabolites after organ injury.

methodsData from the Chronic Renal Insufficiency Cohort (CRIC; n = 3598) were used to study associations between serum uric acid and single nucleotide polymorphisms (SNPs) on the following uric acid transporters: ABCG2 (BRCP), SLC22A6 (OAT1), SLC22A8 (OAT3), SLC22A10 (OAT5), SLC22A11 (OAT4), SLC22A12 (URAT1), SLC22A13 (OAT10), SLC17A1-A3 (NPTs), SLC2A9 (GLUT9), ABCC2 (MRP2) and ABCC4 (MRP4). Regression models, controlling for principal components age, gender and renal function, were run separately for those of European (EA) and African ancestry (AA), and P-values corrected for multiple comparisons. A twin cohort with participants of EA and normal renal function was used for comparison.

resultsAmong those of EA in CRIC, statistically significant signals were observed for SNPs in ABCG2 (rs4148157; beta-coefficient = 0.68; P = 4.78E-13) and SNPs in SLC2A9 (rs13125646; beta-coefficient = -0.30; P = 1.06E-5). Among those of AA, the strongest (but not statistically significant) signals were observed for SNPs in SLC2A9, followed by SNPs in ABCG2. In the twin study (normal renal function), only SNPs in SLC2A9 were significant (rs4481233; beta-coefficient=-0.45; P = 7.0E-6). In CRIC, weaker associations were also found for SLC17A3 (NPT4) and gender-specific associations found for SLC22A8 (OAT3), SLC22A11 (OAT4), and ABCC4 (MRP4).

conclusionsIn patients of EA with CKD (CRIC cohort), we found striking associations between uric acid and SNPs on ABCG2, a key transporter of uric acid by intestine. Compared with ABCG2, SLC2A9 played a much less significant role in this subset of patients with CKD. SNPs in other SLC (e.g. SLC22A8 or OAT3) and ABC (e.g. ABCC4 or MRP4) genes appear to make a weak gender-dependent contribution to uric acid homeostasis in CKD. As renal urate transport is affected in the setting of declining kidney function, extra-renal ABCG2 appears to play a compensatory role-a notion consistent with animal studies and the Remote Sensing and Signaling Hypothesis. Overall, the data indicate how different urate transporters become more or less important depending on renal function, ethnicity and gender. Therapies focused on enhancing ABCG2 urate handling may be helpful in the setting of CKD and hyperuricemia.

Indexed as

ABCG2CKDgastrointestinal transportsex interactionSLC2A9

Identifiers

PMID27274832
PMCPMC4886906
OpenAlexW2337785552

What OpenQuestion holds

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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.