Evidence mapPaperPMID 38314444Full record

ArticleActa physiologica (Oxford, England)2024

SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.

Loïs A K van der Pluijm, Angela Koudijs, Wendy Stam, Joris J T H Roelofs, A H Jan Danser, Joris I Rotmans, Kenneth W Gross, Michael P Pieper, Anton Jan van Zonneveld, Roel Bijkerk

Open access · hybridAbstract read
In one paragraph

Article in Acta physiologica (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. SGLT2 inhibitors and acute kidney injury.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Review
  5. Article
  6. Article
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

10 authors at 5 institutions in 3 countries.

Loïs A K van der PluijmDepartment of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Leiden, the Netherlands.ORCID 0000-0002-2111-3296
Angela KoudijsDepartment of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Wendy StamDepartment of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Joris J T H RoelofsDepartment of Pathology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
A H Jan DanserDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Joris I RotmansDepartment of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Kenneth W GrossDepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Michael P PieperCardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riss, Germany.
Anton Jan van ZonneveldDepartment of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Roel BijkerkDepartment of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Leiden, the Netherlands.
Leiden University Medical Center · NLAmsterdam University Medical Centers · NLBoehringer Ingelheim (Germany) · DEErasmus MC · NLRoswell Park Comprehensive Cancer Center · US

Funding

Tumor Immunology and ImmunotherapyP30CA016056 · ROSWELL PARK CANCER INSTITUTE CORP · 1985 to 2025
$19.4M
NCI NIH HHS P30 CA016056NCI NIH HHS P30CAO16056
6 · The paper itself

Abstract

aimSodium glucose co-transporter-2 (SGLT2) inhibitors stimulate renal excretion of sodium and glucose and exert renal protective effects in patients with (non-)diabetic chronic kidney disease (CKD) and may as well protect against acute kidney injury (AKI). The mechanism behind this kidney protective effect remains unclear. Juxtaglomerular cells of renin lineage (CoRL) have been demonstrated to function as progenitors for multiple adult glomerular cell types in kidney disease. This study assesses the impact of SGLT2 inhibition on the repopulation of glomerular cells by CoRL and examines their phenotypic commitment.

methodsExperiments were performed in Ren1cre-tdTomato lineage-trace mice. Either 5/6 nephrectomy (5/6NX) modeling CKD or bilateral ischaemia reperfusion injury (bIRI) mimicking AKI was applied, while the SGLT2 inhibitor empagliflozin (10 mg/kg) was administered daily via oral gavage for 14 days.

resultsBoth 5/6NX and bIRI-induced kidney injury increased the number of glomerular CoRL-derived cells. SGLT2 inhibition improved kidney function after 5/6NX, indicated by decreased blood creatinine and urea levels, but not after bIRI. In line with this, empagliflozin in 5/6NX animals resulted in less glomerulosclerosis, while it did not affect histopathological features in bIRI. Treatment with empagliflozin resulted in an increase in the number of CoRL-derived glomerular cells in both 5/6NX and bIRI conditions. Interestingly, SGLT2 inhibition led to more CoRL-derived podocytes in 5/6NX animals, whereas empagliflozin-treated bIRI mice presented with increased levels of parietal epithelial and mesangial cells derived from CoRL.

conclusionWe conclude that SGLT2 inhibition by empagliflozin promotes CoRL-mediated glomerular repopulation with selective CoRL-derived cell types depending on the type of experimental kidney injury. These findings suggest a previously unidentified mechanism that could contribute to the renoprotective effect of SGLT2 inhibitors.

Indexed as

Acute Kidney InjuryBenzhydryl CompoundsGlucosidesRed Fluorescent ProteinRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsAnimalsGlucoseHumansMiceReninSodiumSodium-Glucose Transporter 2Benzhydryl CompoundsempagliflozinGlucoseGlucosidesRed Fluorescent ProteinReninSodiumSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorstdTomatocells of renin lineagekidney repairprogenitorRAASregenerationSGLT2 inhibition

Identifiers

PMID38314444
PMCPMC10923162
OpenAlexW4391613211

What Socratic 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 Socratic graph.