Evidence map›Paper›PMID 30921791›Full record

ArticleAmerican journal of nephrology2019

Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus.

T Cooper Woods, Ryousuke Satou, Kayoko Miyata, Akemi Katsurada, Courtney M Dugas, Natasha C Klingenberg, Vivian A Fonseca, L Gabriel Navar

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

Article in American journal of nephrology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
13.4field-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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
  2. How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Trial
  3. Trial
  4. Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022
    Trial
  5. GLP-1 receptor agonists-a potential therapy for chronic kidney disease?Clinical science (London, England : 1979) · 2026
    Review
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  7. Observational
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  16. SGLT2-Inhibition in Patients With Alport Syndrome.Kidney international reports · 2024
    Article
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  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

T Cooper WoodsDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA, twoods3@tulane.edu.
Ryousuke SatouDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Kayoko MiyataDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Akemi KatsuradaDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Courtney M DugasDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Natasha C KlingenbergDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Vivian A FonsecaDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
L Gabriel NavarDepartments of Physiology and of Medicine and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Tulane University · US

Funding

Tracking & Evaluation CoreU54GM104940 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI Leigh Lamonica · 2012 to 2026
$69.1M
Translational Research in Hypertension and Renal BiologyP30GM103337 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI NAVAR, LUIS GABRIEL · 2012 to 2016
$5.8M
Role of VSMC-Derived Exosomes in the Cardiovascular Complications of DiabetesR01HL127092 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI WOODS, THOMAS COOPER · 2016 to 2019
$1.5M
Histone deacetylase 9 is an epigenetic suppressor of intrarenal angiotensinogen, serving as a key mechanism in angiotensinogen augmentation in hypertensionR01DK107694 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI SATO, RYOSUKE · 2016 to 2020
$1.4M
NHLBI NIH HHS R01 HL127092NIDDK NIH HHS R01 DK107694NIGMS NIH HHS P30 GM103337NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

backgroundHypertension and renal injury are common complications of type 2 diabetes mellitus (T2DM). Hyperglycemia stimulates renal proximal tubular angiotensinogen (AGT) expression via elevated oxidative stress contributing to the development of high blood pressure and diabetic nephropathy. The sodium glucose cotransporter 2 (SGLT2) in proximal tubules is responsible for the majority of glucose reabsorption by renal tubules. We tested the hypothesis that SGLT2 inhibition with canagliflozin (CANA) prevents intrarenal AGT augmentation and ameliorates kidney injury and hypertension in T2DM.

methodsWe induced T2DM in New Zealand obese mice with a high fat diet (DM, 30% fat) with control mice receiving regular fat diet (ND, 4% fat). When DM mice exhibited > 350 mg/dL blood glucose levels, both DM- and ND-fed mice were treated with 10 mg/kg/day CANA or vehicle by oral gavage for 6 weeks. We evaluated intrarenal AGT, blood pressure, and the development of kidney injury.

resultsSystolic blood pressure in DM mice (133.9 ± 2.0 mm Hg) was normalized by CANA (113.9 ± 4.0 mm Hg). CANA treatment ameliorated hyperglycemia-associated augmentation of renal AGT mRNA (148 ± 21 copies/ng RNA in DM, and 90 ± 16 copies/ng RNA in DM + CANA) and protein levels as well as elevation of urinary 8-isoprostane levels. Tubular fibrosis in DM mice (3.4 ± 0.9-fold, fibrotic score, ratio to ND) was suppressed by CANA (0.9 ± 0.3-fold). Furthermore, CANA attenuated DM associated increased macrophage infiltration and cell proliferation in kidneys of DM mice.

conclusionsCANA prevents intrarenal AGT upregulation and oxidative stress and which may mitigate high blood pressure, renal tubular fibrosis, and renal inflammation in T2DM.

Indexed as

AngiotensinogenAnimalsBlood GlucoseBlood PressureCanagliflozinDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Diabetic NephropathiesDiet, High-FatFibrosisHumansHypertensionKidney Tubules, ProximalMiceOxidative StressSodium-Glucose Transporter 2 InhibitorsAgt protein, mouseAngiotensinogenBlood GlucoseCanagliflozinSodium-Glucose Transporter 2 InhibitorsAngiotensinogenBlood pressureDiabetes mellitusKidneySodium glucose cotransporter 2 inhibition

Identifiers

PMID30921791
PMCPMC6475450
OpenAlexW2929005364

What OpenQuestion holds

Texttitle and abstract
LicenceTDM
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.