{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:00:36Z","timestamp":1789617636810,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K11555"],"award-info":[{"award-number":["25K11555"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009158","name":"Kawasaki Medical School","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009158","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022274","name":"Daiichi Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heart and Stroke Richard Lewar Centre of Excellence"},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) is a major cause of chronic kidney disease, with glomerular hyperfiltration contributing to its progression. Esaxerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA), reduces albuminuria, but its precise mechanism remains unclear. Mineralocorticoid receptor (MR) activation is implicated in tubuloglomerular feedback (TGF) dysregulation, and we hypothesized that MR inhibition attenuates albuminuria by mitigating glomerular hyperfiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the effects of esaxerenone, we used aldosterone-induced MR activation rats and type 2 diabetic (db\/db) mice. In vivo multiphoton imaging was performed to assess the single-nephron glomerular filtration rate (SNGFR) and arteriolar diameters. Macula densa (MD) cells were used to examine MR activation\u2019s impact on TGF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In aldosterone-infused rats, MR activation induced glomerular hyperfiltration via afferent arteriolar dilation, which was attenuated by esaxerenone. In db\/db mice, esaxerenone reduced SNGFR and urinary albumin excretion while increasing urinary adenosine levels, effects reversed by A1aR blockade. In MD cells, MR activation increased nitric oxide (NO) production and reduced Na+-K+-2Cl\u2212 cotransporter membrane expression, both of which were mitigated by MRA or neuronal nitric oxide synthase inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that esaxerenone restores TGF function via adenosine signalling, attenuating glomerular hyperfiltration and reducing albuminuria. This study provides novel insights into the albuminuria-lowering effects of MR blockade in DKD and supports the therapeutic potential of esaxerenone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf232","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:02:33Z","timestamp":1762671753000},"page":"1069-1081","source":"Crossref","is-referenced-by-count":4,"title":["The non-steroidal mineralocorticoid receptor blocker esaxerenone reduces glomerular hyperfiltration and albuminuria"],"prefix":"10.1093","volume":"41","author":[{"given":"Rie","family":"Tatsugawa","sequence":"first","affiliation":[{"name":"Kawasaki Medical School Department of Nephrology and Hypertension, , Kurashiki, Okayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Kidokoro","sequence":"additional","affiliation":[{"name":"Kawasaki Medical School Department of Nephrology and Hypertension, , Kurashiki, Okayama 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