ArticleActa physiologica (Oxford, England)2024
SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.
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.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Nanotechnology-mediated podocyte injury repair: mechanistic exploration and therapeutic prospects.Renal failure · 2026Review
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Post-nephrectomy outcomes in COVID-19 and non-COVID-19 Patients using ACEi, ARB and SGLT2i: a N3C database study.International urology and nephrology · 2026Article
- SGLT2 inhibitors and acute kidney injury.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- Effects of sotagliflozin on kidney and cardiac outcome in a hypertensive model of subtotal nephrectomy in male mice.Physiological reports · 2025Article
- Commentary: the perspectives of harnessing the power of scattered tubular-like cells for renal repair.Clinical science (London, England : 1979) · 2024Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
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.
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