Evidence mapPaperPMID 23949796Full record

ArticleJournal of the American Society of Nephrology : JASN2013

Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease.

Kumar Sharma, Bethany Karl, Anna V Mathew, Jon A Gangoiti, Christina L Wassel, Rintaro Saito, Minya Pu, Shoba Sharma, Young-Hyun You, Lin Wang and 14 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03933956 (Metabolic Effects of the SGLT-2 Inhibitor Empagliflozin in Patients With Diabetic Nephropathy), which is not on this map. Cited by 323 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
323citing papers in PubMed, 3 pooled it
15.7field-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.

NCT03933956 phase3terminatedstarted 2020, after this paper: background citation

Metabolic Effects of the SGLT-2 Inhibitor Empagliflozin in Patients With Diabetic Nephropathy (MEDiaN)

Ran2020Enrolled2Registered outcomes3Posted comparisons0ConditionsDiabetic NephropathiesArmsempagliflozin 10 mg
Open the trial in the graph
3 · Its place in the literature

Who cites it

323 citing papers in PubMed, 3 syntheses or guidelines pooled it, 566 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
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  13. Urinary biomarkers of diabetic kidney disease.World journal of diabetes · 2026
    Review
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  16. Review
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263 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

24 authors at 5 institutions in 4 countries.

Kumar SharmaInstitute of Metabolomic Medicine.
Bethany Karl
Anna V Mathew
Jon A Gangoiti
Christina L Wassel
Rintaro Saito
Minya Pu
Shoba Sharma
Young-Hyun You
Lin Wang
Maggie Diamond-Stanic
Maja T Lindenmeyer
Carol Forsblom
Wei Wu
Joachim H Ix
Trey Ideker
Jeffrey B Kopp
Sanjay K Nigam
Clemens D Cohen
Per-Henrik Groop
Bruce A Barshop
Loki Natarajan
William L Nyhan
Robert K Naviaux
Center for Translational Molecular Medicine · NLMedical Genetics Center · DEVA San Diego Healthcare System · USPediatrics and Genetics · USGeneral Department of Preventive Medicine · VN

Funding

BLRD VA I01 BX000277NIDDK NIH HHS 1DP3DK094352NIDDK NIH HHS DP3 DK094352NIGMS NIH HHS P41 GM103504NIGMS NIH HHS P41GM103504NIGMS NIH HHS P50 GM085764NIGMS NIH HHS R01 GM098449
6 · The paper itself

Abstract

Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM-CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease.

Indexed as

AdultAgedDiabetic NephropathiesFemaleGlomerular Filtration RateHumansIon TransportMaleMetabolomicsMiddle AgedMitochondrial DiseasesOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaRenal Insufficiency, ChronicTranscription FactorsOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1organic anion transport protein 3Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanTranscription Factors

Identifiers

PMID23949796
PMCPMC3810086
OpenAlexW2108822380

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.