{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:47:34Z","timestamp":1774673254587,"version":"3.50.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Steroidal mineralocorticoid receptor antagonists (MRAs) form a cornerstone of the management of heart failure (HF), but little is known about the long\u2010term effects of MRA therapy on kidney function. We evaluated acute and chronic estimated glomerular function (eGFR) slopes in the two largest completed trials testing steroidal MRAs in chronic HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We conducted parallel\n                      <jats:italic>post hoc<\/jats:italic>\n                      eGFR slope analyses in two multinational, double\u2010blind randomized, placebo\u2010controlled trials of steroidal MRAs in chronic HF with reduced ejection fraction (EMPHASIS\u2010HF) and preserved ejection fraction (TOPCAT Americas region). GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Annual slopes of eGFR were assessed by generalized random coefficient models. Least square mean differences in eGFR slopes between steroidal MRA and placebo arms were assessed. Median follow\u2010up was 1.8\u2009years (EMPHASIS\u2010HF) and 3.3\u2009years (TOPCAT Americas). From baseline to month 4\u20136 (\u2018acute eGFR slope\u2019), compared to placebo, MRA treatment led to an acute decline in eGFR of \u22122.4\u00a0ml\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      (95% confidence interval [CI] \u22123.4 to \u22121.4;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and \u22122.0\u00a0ml\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      (95% CI \u22123.0 to \u22121.8;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) in EMPHASIS\u2010HF and TOPCAT Americas, respectively. From month 4\u20136 to end of study, there was no difference in \u2018chronic eGFR slope\u2019 between MRA and placebo arms (\u22120.3\u00a0ml\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      \/year [95% CI \u22121.3 to 0.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.53] and 0.1\u00a0ml\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      \/year [95% CI \u22121.4 to 1.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.86]) in EMPHASIS\u2010HF and TOPCAT Americas, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Steroidal MRAs result in acute declines in eGFR but do not modify long\u2010term kidney disease trajectories in chronic HF with reduced or preserved ejection fraction.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: EMPHASIS\u2010HF (ClinicalTrials.gov NCT00232180) and TOPCAT (ClinicalTrials.gov NCT00094302).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2635","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T14:33:17Z","timestamp":1658500397000},"page":"1586-1590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Effects of steroidal mineralocorticoid receptor antagonists on acute and chronic estimated glomerular filtration rate slopes in patients with chronic heart failure"],"prefix":"10.1093","volume":"24","author":[{"given":"Muthiah","family":"Vaduganathan","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm 1433 CIC\u2010P CHRU de Nancy, Inserm U1116 and FCRIN INI\u2010CRCT  Nancy France"},{"name":"UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto  Porto Portugal"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm 1433 CIC\u2010P CHRU de Nancy, Inserm U1116 and FCRIN INI\u2010CRCT  Nancy France"},{"name":"Department of Medical specialties and Nephrology\u2010Hemodialysis, Princess Grace Hospital, Monaco, and Centre d'H\u00e9modialyse Priv\u00e9 de Monaco  Monaco"}]},{"given":"Brendon L.","family":"Neuen","sequence":"additional","affiliation":[{"name":"George Institute for Global Health and University of New South Wales  Sydney New South Wales Australia"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre University of Glasgow  Glasgow UK"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"University of Michigan School of Medicine  Ann Arbor MI USA"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm 1433 CIC\u2010P CHRU de Nancy, Inserm U1116 and FCRIN INI\u2010CRCT  Nancy France"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}]}],"member":"286","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.12.057"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.07.048"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.04.086"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003588"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.028282"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000792"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.06.009"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013255"},{"key":"e_1_2_5_10_1","first-page":"S1","article-title":"KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease\u2010mineral and bone disorder (CKD\u2010MBD)","volume":"113","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD\u2010MBD Work Group","year":"2009","journal-title":"Kidney Int Suppl"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1909"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1400"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002187"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.01.087"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.609"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2036175"}],"container-title":["European Journal of Heart 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