{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:03:24Z","timestamp":1792029804638,"version":"4.4.0"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Sodium\u2010glucose co\u2010transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This post\u2010hoc analysis utilized data of the\n                      <jats:styled-content style=\"fixed-case\">ROTATE<\/jats:styled-content>\n                      \u20103 study, a randomized cross\u2010over study in 46 adults with chronic kidney disease and urinary albumin excretion \u2265100\u2009mg\/24\u2009h, who were treated for 4\u2009weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro\u2010hormonal markers and tubular sodium handling were assessed with mixed repeated measures models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean percentage change from baseline in heparan sulphate after 4\u2009weeks treatment with dapagliflozin, eplerenone or dapagliflozin\u2010eplerenone was \u221234.8% (95% CI \u221252.2, \u221210.9), \u22125.9% (95% CI \u221232.5, 31.3) and \u221228.1% (95% CI \u221248.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin\u2010eplerenone [32.2% (95% CI \u22121.5, 77.4)], compared with dapagliflozin [\u221212.5% (95% CI \u221235.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin\u2010eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI \u221210.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9\u2009mmol\/min (95% CI \u2212879.2, \u221232.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1\u2009mmol\/min (95% CI \u2212926.1, \u2212120.0). Dapagliflozin\u2010eplerenone decreased proximal absolute sodium reabsorption [\u2212971.0\u2009mmol\/min (95% CI \u22121411.0, \u2212531.0)], but did not affect distal absolute sodium reabsorption [\u22129.2\u2009mmol\/min (95% CI \u2212402.0, 383.6)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15346","type":"journal-article","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T23:36:11Z","timestamp":1699227371000},"page":"576-582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Glomerular and tubular effects of dapagliflozin, eplerenone and their combination in patients with chronic kidney disease: A post\u2010hoc analysis of the\n                    <scp>ROTATE<\/scp>\n                    \u20103 study"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6808-3198","authenticated-orcid":false,"given":"Tom T. G. F.","family":"Lieverse","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Puchades","sequence":"additional","affiliation":[{"name":"Department of Nephrology University Clinical Hospital Valencia, INCLIVA, University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo D. J.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Vascular Medicine University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Provenzano","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Renal Transplant Unit IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC) Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Krenning","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Jongs","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon E.","family":"Wink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riemer H. J. A.","family":"Slart","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Andreucci","sequence":"additional","affiliation":[{"name":"Department of Health Sciences 'Magna Graecia' University of Catanzaro  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-891X","authenticated-orcid":false,"given":"Luis","family":"D'Marco","sequence":"additional","affiliation":[{"name":"Universidad Cardenal Herrera\u2010CEU, CEU Universities  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Nicola","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University L. Vanvitelli  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Gorriz","sequence":"additional","affiliation":[{"name":"Department of Nephrology University Clinical Hospital Valencia, INCLIVA, University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020050723"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2022020207\/\u2010\/DCSUPPLEMENTAL"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/NRNEPH.2015.162"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/NDT\/GFT410"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.KINT.2018.08.024"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/BPH.15850"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11010\u2010019\u201003555\u20102"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41581\u2010020\u201000350\u2010X"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.33176\/AACB\u201020\u201000001"},{"key":"e_1_2_10_11_1","unstructured":"R Core Team.R: A Language and Enironment for Statistical Computing.2017https:\/\/www.R-project.org"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00533.2014"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/DIABETES.55.04.06.DB05\u20101619"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.DIABET.2019.11.006"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048739"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2024816\/SUPPL_FILE\/NEJMOA2024816_DATA\u2010SHARING.PDF"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/DC22\u20100866\/687934\/DC220866.PDF"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/DOM.14779"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04117"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010022\u201002321\u20103"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.15346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:47:28Z","timestamp":1761868048000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.15346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,5]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/dom.15346"],"URL":"https:\/\/doi.org\/10.1111\/dom.15346","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.15346\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15346\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15346\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15346\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15346\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,5]]},"assertion":[{"value":"2023-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}