Evidence map›Paper›PMID 25369239›Full record

ArticlePloS one2014

Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

Muralikrishna Gangadharan Komala, Simon Gross, Harshini Mudaliar, Chunling Huang, Katherine Pegg, Amanda Mather, Sylvie Shen, Carol A Pollock, Usha Panchapakesan

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
6.4field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

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  17. SGLT2 inhibition to address the unmet needs in diabetic nephropathy.Diabetes/metabolism research and reviews · 2019
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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

9 authors at 2 institutions in 1 country.

Muralikrishna Gangadharan KomalaRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Simon GrossRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Harshini MudaliarRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Chunling HuangRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Katherine PeggRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Amanda MatherRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Sylvie ShenRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Carol A PollockRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Usha PanchapakesanRenal Research Lab, Kolling Institute of Medical Research, Sydney University, Royal North Shore Hospital, St Leonards, Australia.
Royal North Shore Hospital · AUUniversity of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveSodium glucose cotransporter 2 (SGLT2) is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND

methodsWe induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS) synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice).

resultsDiabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1), transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the different groups.

conclusionHence SGLT2 inhibition does not have renoprotective benefits independent of glucose lowering.

Indexed as

AlbuminuriaAnimalsBenzhydryl CompoundsBenzimidazolesBenzoatesBlood GlucoseChemokine CCL2Diabetes Mellitus, ExperimentalDiabetic NephropathiesFibronectinsGlucose Transporter Type 1GlucosidesHypoglycemic AgentsKidney Tubules, ProximalMaleMiceBenzhydryl CompoundsBenzimidazolesBenzoatesBlood GlucoseCcl2 protein, mouseChemokine CCL2empagliflozinFibronectinsGlucose Transporter Type 1GlucosidesHypoglycemic AgentsNitric Oxide Synthase Type IIIRNA, MessengerSlc2a1 protein, mouseSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsStreptozocinTelmisartanToll-Like Receptor 2Transforming Growth Factor beta1

Identifiers

PMID25369239
PMCPMC4219667
OpenAlexW2021825265

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.