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

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Title: SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.
Authors: van der Pluijm, Loïs A. K. (AUTHOR), Koudijs, Angela (AUTHOR), Stam, Wendy (AUTHOR), Roelofs, Joris J. T. H. (AUTHOR), Danser, A. H. Jan (AUTHOR), Rotmans, Joris I. (AUTHOR), Gross, Kenneth W. (AUTHOR), Pieper, Michael P. (AUTHOR), van Zonneveld, Anton Jan (AUTHOR), Bijkerk, Roel (AUTHOR)
Source: Acta Physiologica. Mar2024, Vol. 240 Issue 3, p1-14. 14p.
Subjects: Empagliflozin, Kidney diseases, Renin, Sodium-glucose cotransporter 2 inhibitors, Acute kidney failure, Chronic kidney failure
Abstract: Aim: Sodium 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. Methods: Experiments 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. Results: Both 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. Conclusion: We 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. [ABSTRACT FROM AUTHOR]
Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.
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  Data: <searchLink fieldCode="AR" term="%22van+der+Pluijm%2C+Loïs+A%2E+K%2E%22">van der Pluijm, Loïs A. K.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Koudijs%2C+Angela%22">Koudijs, Angela</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stam%2C+Wendy%22">Stam, Wendy</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roelofs%2C+Joris+J%2E+T%2E+H%2E%22">Roelofs, Joris J. T. H.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Danser%2C+A%2E+H%2E+Jan%22">Danser, A. H. Jan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rotmans%2C+Joris+I%2E%22">Rotmans, Joris I.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gross%2C+Kenneth+W%2E%22">Gross, Kenneth W.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pieper%2C+Michael+P%2E%22">Pieper, Michael P.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22van+Zonneveld%2C+Anton+Jan%22">van Zonneveld, Anton Jan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bijkerk%2C+Roel%22">Bijkerk, Roel</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Physiologica%22">Acta Physiologica</searchLink>. Mar2024, Vol. 240 Issue 3, p1-14. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Empagliflozin%22">Empagliflozin</searchLink><br /><searchLink fieldCode="DE" term="%22Kidney+diseases%22">Kidney diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Renin%22">Renin</searchLink><br /><searchLink fieldCode="DE" term="%22Sodium-glucose+cotransporter+2+inhibitors%22">Sodium-glucose cotransporter 2 inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22Acute+kidney+failure%22">Acute kidney failure</searchLink><br /><searchLink fieldCode="DE" term="%22Chronic+kidney+failure%22">Chronic kidney failure</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Aim: Sodium 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. Methods: Experiments 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. Results: Both 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. Conclusion: We 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1111/apha.14108
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      – Code: eng
        Text: English
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        PageCount: 14
        StartPage: 1
    Subjects:
      – SubjectFull: Empagliflozin
        Type: general
      – SubjectFull: Kidney diseases
        Type: general
      – SubjectFull: Renin
        Type: general
      – SubjectFull: Sodium-glucose cotransporter 2 inhibitors
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      – SubjectFull: Acute kidney failure
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      – SubjectFull: Chronic kidney failure
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      – TitleFull: SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.
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              Text: Mar2024
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