Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease
Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2) leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin sys...
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| description | Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2) leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally) nephrectomised rats, a model of progressive chronic kidney disease (CKD) that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD. |
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As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally) nephrectomised rats, a model of progressive chronic kidney disease (CKD) that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0144640</identifier><identifier>PMID: 26741142</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiotensin ; Animals ; Barotrauma ; Benzhydryl Compounds - pharmacology ; Care and treatment ; Causes of ; Chronic kidney failure ; Diabetes ; Diabetes mellitus ; Disease Models, Animal ; Disease Progression ; Enzyme inhibitors ; Enzymes ; Fibrosis ; Gene Expression ; Glomerular Filtration Rate ; Glucose ; Glucosides - pharmacology ; Glycosuria - drug therapy ; Glycosuria - etiology ; Glycosuria - metabolism ; Glycosuria - pathology ; Growth factors ; Humans ; Hyperfiltration ; Hypertension ; Hypertension, Renal - drug therapy ; Hypertension, Renal - etiology ; Hypertension, Renal - metabolism ; Hypertension, Renal - pathology ; Hypertrophy ; Hypoglycemic Agents - pharmacology ; Hypotheses ; Inhibition ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Kidney diseases ; Kidneys ; Laboratory animals ; Laboratory rats ; Male ; mRNA ; Nephrectomy - adverse effects ; Peptidyl-dipeptidase A ; Pharmacology ; Proteinuria ; Proteinuria - drug therapy ; Proteinuria - etiology ; Proteinuria - metabolism ; Proteinuria - pathology ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic - drug therapy ; Renal Insufficiency, Chronic - etiology ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - pathology ; Renin ; Risk factors ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Sodium ; Sodium-Glucose Transporter 2 - genetics ; Sodium-Glucose Transporter 2 - metabolism ; Sodium-Glucose Transporter 2 Inhibitors ; Surgery ; Transforming growth factor ; Transforming Growth Factor beta1 - genetics ; Transforming Growth Factor beta1 - metabolism ; Treatment Failure ; Urine</subject><ispartof>PloS one, 2016-01, Vol.11 (1), p.e0144640-e0144640</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally) nephrectomised rats, a model of progressive chronic kidney disease (CKD) that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.</description><subject>Angiotensin</subject><subject>Animals</subject><subject>Barotrauma</subject><subject>Benzhydryl Compounds - pharmacology</subject><subject>Care and treatment</subject><subject>Causes of</subject><subject>Chronic kidney failure</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Enzyme inhibitors</subject><subject>Enzymes</subject><subject>Fibrosis</subject><subject>Gene Expression</subject><subject>Glomerular Filtration Rate</subject><subject>Glucose</subject><subject>Glucosides - pharmacology</subject><subject>Glycosuria - drug therapy</subject><subject>Glycosuria - etiology</subject><subject>Glycosuria - metabolism</subject><subject>Glycosuria - pathology</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hyperfiltration</subject><subject>Hypertension</subject><subject>Hypertension, Renal - drug therapy</subject><subject>Hypertension, Renal - etiology</subject><subject>Hypertension, Renal - metabolism</subject><subject>Hypertension, Renal - pathology</subject><subject>Hypertrophy</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Hypotheses</subject><subject>Inhibition</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Laboratory animals</subject><subject>Laboratory rats</subject><subject>Male</subject><subject>mRNA</subject><subject>Nephrectomy - adverse effects</subject><subject>Peptidyl-dipeptidase A</subject><subject>Pharmacology</subject><subject>Proteinuria</subject><subject>Proteinuria - drug therapy</subject><subject>Proteinuria - etiology</subject><subject>Proteinuria - metabolism</subject><subject>Proteinuria - pathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Renal Insufficiency, Chronic - drug therapy</subject><subject>Renal Insufficiency, Chronic - etiology</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Renin</subject><subject>Risk factors</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Sodium</subject><subject>Sodium-Glucose Transporter 2 - genetics</subject><subject>Sodium-Glucose Transporter 2 - metabolism</subject><subject>Sodium-Glucose Transporter 2 Inhibitors</subject><subject>Surgery</subject><subject>Transforming growth factor</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Treatment Failure</subject><subject>Urine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk81u1DAUhSMEolB4AwSWkBAsZvBfnGSDVE2hjCgUtcDWcpzrGZeMPdgOoo_BG-PQtOqgLlAWjq6_c2wf-xbFE4LnhFXk9bkfglP9fOsdzDHhXHB8p3hAGkZngmJ298b_XvEwxnOMS1YLcb_Yo6LihHD6oPh95js7bGZH_aB9BHRs3Xfo0MKnoFzc-pAgzChaurVtbbLeoUMPEX3yCR2kBG5QCdChjaCy-HPwqwAxjph1KK0BnaqETmHjlEvog-0cXKCPvoMeeYMW6-Cd1Vf1yeVRcc-oPsLjadwvvr57-2XxfnZ8crRcHBzPtGhomgnSKqy6thREG8IrY3RrOKlpjkHUba24FkZz02LcYANAOqJ0WWtMoW4MKdl-8ezSd9v7KKc0oyRVyUtKWM5uv1heEp1X53Ib7EaFC-mVlX8LPqykCsnqHiThqqF1p6sKgNNWNIorXpeMqhw6LUX2ejOtNrQb6DS4HHC_Y7o74-xarvxPyStCasyywcvJIPgfA8QkNzZq6HvlwA_jvgWua8ZpldHn_6C3n26iViofwDozXrkeTeUBZw1lVcPGfc9vofLXwcbq_PSMzfUdwasdQWYS_EorNcQol2en_8-efNtlX9xg16D6tI6-H8Y3GXdBfgnq4GMMYK5DJliOnXOVhhw7R06dk2VPb17QteiqVdgfd7sUKQ</recordid><startdate>20160107</startdate><enddate>20160107</enddate><creator>Zhang, Yanling</creator><creator>Thai, Kerri</creator><creator>Kepecs, David M</creator><creator>Gilbert, Richard E</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160107</creationdate><title>Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease</title><author>Zhang, Yanling ; Thai, Kerri ; Kepecs, David M ; Gilbert, Richard E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-61ba0adb561cf147ffcbf418264068b8a4c6fc4fb0090fee1d1ac58c02e89f153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Angiotensin</topic><topic>Animals</topic><topic>Barotrauma</topic><topic>Benzhydryl Compounds - pharmacology</topic><topic>Care and treatment</topic><topic>Causes of</topic><topic>Chronic kidney failure</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Enzyme inhibitors</topic><topic>Enzymes</topic><topic>Fibrosis</topic><topic>Gene Expression</topic><topic>Glomerular Filtration Rate</topic><topic>Glucose</topic><topic>Glucosides - pharmacology</topic><topic>Glycosuria - drug therapy</topic><topic>Glycosuria - etiology</topic><topic>Glycosuria - metabolism</topic><topic>Glycosuria - pathology</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hyperfiltration</topic><topic>Hypertension</topic><topic>Hypertension, Renal - drug therapy</topic><topic>Hypertension, Renal - etiology</topic><topic>Hypertension, Renal - metabolism</topic><topic>Hypertension, Renal - pathology</topic><topic>Hypertrophy</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Hypotheses</topic><topic>Inhibition</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Laboratory animals</topic><topic>Laboratory rats</topic><topic>Male</topic><topic>mRNA</topic><topic>Nephrectomy - adverse effects</topic><topic>Peptidyl-dipeptidase A</topic><topic>Pharmacology</topic><topic>Proteinuria</topic><topic>Proteinuria - drug therapy</topic><topic>Proteinuria - etiology</topic><topic>Proteinuria - metabolism</topic><topic>Proteinuria - pathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Renal Insufficiency, Chronic - drug therapy</topic><topic>Renal Insufficiency, Chronic - etiology</topic><topic>Renal Insufficiency, Chronic - metabolism</topic><topic>Renal Insufficiency, Chronic - pathology</topic><topic>Renin</topic><topic>Risk factors</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Sodium</topic><topic>Sodium-Glucose Transporter 2 - genetics</topic><topic>Sodium-Glucose Transporter 2 - metabolism</topic><topic>Sodium-Glucose Transporter 2 Inhibitors</topic><topic>Surgery</topic><topic>Transforming growth factor</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Treatment Failure</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yanling</creatorcontrib><creatorcontrib>Thai, Kerri</creatorcontrib><creatorcontrib>Kepecs, David M</creatorcontrib><creatorcontrib>Gilbert, Richard E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yanling</au><au>Thai, Kerri</au><au>Kepecs, David M</au><au>Gilbert, Richard E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-01-07</date><risdate>2016</risdate><volume>11</volume><issue>1</issue><spage>e0144640</spage><epage>e0144640</epage><pages>e0144640-e0144640</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2) leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally) nephrectomised rats, a model of progressive chronic kidney disease (CKD) that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26741142</pmid><doi>10.1371/journal.pone.0144640</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1754521319 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Angiotensin Animals Barotrauma Benzhydryl Compounds - pharmacology Care and treatment Causes of Chronic kidney failure Diabetes Diabetes mellitus Disease Models, Animal Disease Progression Enzyme inhibitors Enzymes Fibrosis Gene Expression Glomerular Filtration Rate Glucose Glucosides - pharmacology Glycosuria - drug therapy Glycosuria - etiology Glycosuria - metabolism Glycosuria - pathology Growth factors Humans Hyperfiltration Hypertension Hypertension, Renal - drug therapy Hypertension, Renal - etiology Hypertension, Renal - metabolism Hypertension, Renal - pathology Hypertrophy Hypoglycemic Agents - pharmacology Hypotheses Inhibition Kidney - drug effects Kidney - metabolism Kidney - pathology Kidney diseases Kidneys Laboratory animals Laboratory rats Male mRNA Nephrectomy - adverse effects Peptidyl-dipeptidase A Pharmacology Proteinuria Proteinuria - drug therapy Proteinuria - etiology Proteinuria - metabolism Proteinuria - pathology Rats Rats, Sprague-Dawley Renal Insufficiency, Chronic - drug therapy Renal Insufficiency, Chronic - etiology Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - pathology Renin Risk factors RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Sodium Sodium-Glucose Transporter 2 - genetics Sodium-Glucose Transporter 2 - metabolism Sodium-Glucose Transporter 2 Inhibitors Surgery Transforming growth factor Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - metabolism Treatment Failure Urine |
| title | Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T00%3A42%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sodium-Glucose%20Linked%20Cotransporter-2%20Inhibition%20Does%20Not%20Attenuate%20Disease%20Progression%20in%20the%20Rat%20Remnant%20Kidney%20Model%20of%20Chronic%20Kidney%20Disease&rft.jtitle=PloS%20one&rft.au=Zhang,%20Yanling&rft.date=2016-01-07&rft.volume=11&rft.issue=1&rft.spage=e0144640&rft.epage=e0144640&rft.pages=e0144640-e0144640&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0144640&rft_dat=%3Cgale_plos_%3EA439237936%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1754521319&rft_id=info:pmid/26741142&rft_galeid=A439237936&rft_doaj_id=oai_doaj_org_article_14a928dc77ee42b69a4a48532a005256&rfr_iscdi=true |