Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy
A patient with renal glucosuria due to a congenital knock-out of the sodium-glucose cotransporter 2 (SGLT-2) protein because of a compound heterozygous mutation in the SLC5A2 gene may provide a natural model mimicking the effects of long-term SGLT-2 inhibitor therapy, which has been shown to exert k...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Kidney Medicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259005951930175X |
| _version_ | 1818315188735049728 |
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| author | Hannes Neuwirt Andrea Burtscher David Cherney Gert Mayer Christoph Ebenbichler |
| author_facet | Hannes Neuwirt Andrea Burtscher David Cherney Gert Mayer Christoph Ebenbichler |
| author_sort | Hannes Neuwirt |
| collection | DOAJ |
| description | A patient with renal glucosuria due to a congenital knock-out of the sodium-glucose cotransporter 2 (SGLT-2) protein because of a compound heterozygous mutation in the SLC5A2 gene may provide a natural model mimicking the effects of long-term SGLT-2 inhibitor therapy, which has been shown to exert kidney-protective effects beyond its antidiabetic properties. One possible mechanism for the protective effects of SGLT-2 inhibitor therapy might be the activation of tubuloglomerular feedback by increased outflow of sodium, chloride, and glucose to distal parts of the nephron, including the macula densa. Subsequently, afferent arteriolar vasoconstriction is induced and blood flow, intraglomerular filtration pressure, and glomerular filtration rate (GFR) all decline. However, prolonged tubuloglomerular feedback activation could change the sensitivity of tubuloglomerular feedback and hence decrease the beneficial effects of SGLT-2 inhibition on kidney function. Tubuloglomerular feedback is mediated by the Na+/K+/2Cl− cotransporter. Hence furosemide, which blocks this cotransporter, is a medical option to test tubuloglomerular feedback because GFR should increase after administration of this loop diuretic. In our patient with long-term activated tubuloglomerular feedback due to SGLT-2 mutations, we show that the sensitivity of tubuloglomerular feedback is maintained, demonstrated by an increase in GFR measured using iohexol clearance following furosemide administration. This observation supports the idea that long-term SGLT-2 inhibitor therapy is kidney protective through a functional tubuloglomerular feedback. Index Words: SGLT-2 Inhibitor, glomerular filtration rate, tubuloglomerular feedback, kidney protection, iohexol clearance |
| first_indexed | 2024-12-13T09:01:34Z |
| format | Article |
| id | doaj.art-3f9d62b0c3904ad492b5fa9cb06551e4 |
| institution | Directory Open Access Journal |
| issn | 2590-0595 |
| language | English |
| last_indexed | 2024-12-13T09:01:34Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney Medicine |
| spelling | doaj.art-3f9d62b0c3904ad492b5fa9cb06551e42022-12-21T23:53:09ZengElsevierKidney Medicine2590-05952020-01-01217679Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor TherapyHannes Neuwirt0Andrea Burtscher1David Cherney2Gert Mayer3Christoph Ebenbichler4Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine I (Gastroenterology, Hepatology, and Endocrinology), Medical University Innsbruck, Innsbruck, AustriaDivision of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada; Department of Physiology, University Health Network, University of Toronto, Toronto, CanadaDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria; Address for Correspondence: Gert Mayer, MD, Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.Department of Internal Medicine I (Gastroenterology, Hepatology, and Endocrinology), Medical University Innsbruck, Innsbruck, AustriaA patient with renal glucosuria due to a congenital knock-out of the sodium-glucose cotransporter 2 (SGLT-2) protein because of a compound heterozygous mutation in the SLC5A2 gene may provide a natural model mimicking the effects of long-term SGLT-2 inhibitor therapy, which has been shown to exert kidney-protective effects beyond its antidiabetic properties. One possible mechanism for the protective effects of SGLT-2 inhibitor therapy might be the activation of tubuloglomerular feedback by increased outflow of sodium, chloride, and glucose to distal parts of the nephron, including the macula densa. Subsequently, afferent arteriolar vasoconstriction is induced and blood flow, intraglomerular filtration pressure, and glomerular filtration rate (GFR) all decline. However, prolonged tubuloglomerular feedback activation could change the sensitivity of tubuloglomerular feedback and hence decrease the beneficial effects of SGLT-2 inhibition on kidney function. Tubuloglomerular feedback is mediated by the Na+/K+/2Cl− cotransporter. Hence furosemide, which blocks this cotransporter, is a medical option to test tubuloglomerular feedback because GFR should increase after administration of this loop diuretic. In our patient with long-term activated tubuloglomerular feedback due to SGLT-2 mutations, we show that the sensitivity of tubuloglomerular feedback is maintained, demonstrated by an increase in GFR measured using iohexol clearance following furosemide administration. This observation supports the idea that long-term SGLT-2 inhibitor therapy is kidney protective through a functional tubuloglomerular feedback. Index Words: SGLT-2 Inhibitor, glomerular filtration rate, tubuloglomerular feedback, kidney protection, iohexol clearancehttp://www.sciencedirect.com/science/article/pii/S259005951930175X |
| spellingShingle | Hannes Neuwirt Andrea Burtscher David Cherney Gert Mayer Christoph Ebenbichler Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy Kidney Medicine |
| title | Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy |
| title_full | Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy |
| title_fullStr | Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy |
| title_full_unstemmed | Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy |
| title_short | Tubuloglomerular Feedback in Renal Glucosuria: Mimicking Long-term SGLT-2 Inhibitor Therapy |
| title_sort | tubuloglomerular feedback in renal glucosuria mimicking long term sglt 2 inhibitor therapy |
| url | http://www.sciencedirect.com/science/article/pii/S259005951930175X |
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