{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:17:56Z","timestamp":1792041476984,"version":"4.4.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2017,8]]},"abstract":"\n Background and objectives<\/jats:title>\n We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN).<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml\/min per 1.73 m\n 2<\/jats:sup>\n were included. Patients with BK virus active nephritis, recurrence of renal disease, GFR decline in previous 3 months, or treated with calcium antagonists or antifungal drugs were excluded. They were randomized to receive placebo (\n n<\/jats:italic>\n =10) or eplerenone 25 mg\/d for 24 months (\n n<\/jats:italic>\n =13). Visits were scheduled at baseline, 6, 12, and 24 months. At each period, a complete clinical examination was performed and blood and urine samples were taken. Urine creatinine, 8-hydroxylated-guanosine, heat shock protein 72 (HSP72), and kidney injury molecule (KIM-1) levels were also assessed. In kidney biopsy samples, the tubulo-interstitial area affected by fibrosis (TIF) and glomerulosclerosis were measured at baseline and after 24 months.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The baseline eGFR was 80\u00b16 in the placebo and 86\u00b16 ml\/min per 1.73 m\n 2<\/jats:sup>\n in the eplerenone group; at 24 months it was 66\u00b18 and 81\u00b17 ml\/min per 1.73 m\n 2<\/jats:sup>\n , respectively (\n P<\/jats:italic>\n =0.33; 95% confidence intervals, \u221218 to 33 at baseline, and \u221211 to 40 after 24 months). The albumin-to-creatinine ratio was 110\u00b174 in the placebo, and 265\u00b1140 mg\/g in the eplerenone group; and after 24 months it was 276\u00b1140 and 228\u00b188 mg\/g, respectively (\n P<\/jats:italic>\n =0.15; 95% confidence intervals, \u2212283 to 593, and \u2212485 to 391, respectively). In addition, the placebo exhibited a greater TIF, glomerulosclerosis, and urinary HSP72 compared with the eplerenone group.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Although this study was underpowered to provide definitive evidence that long-term eplerenone administration attenuates the progression of CAN in pediatric transplant patients, it encourages testing the potential benefit of MRB in this pediatric population.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.05300516","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T20:25:33Z","timestamp":1495571133000},"page":"1291-1300","source":"Crossref","is-referenced-by-count":32,"title":["Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft Nephropathy"],"prefix":"10.2215","volume":"12","author":[{"given":"Mara","family":"Medeiros","sequence":"first","affiliation":[{"name":"Nephrology and Mineral Metabolism Research Unit,"},{"name":"Department of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Vel\u00e1squez-Jones","sequence":"additional","affiliation":[{"name":"Department of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Nephrology and Mineral Metabolism Research Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Ram\u00f3n-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Infantil de M\u00e9xico, Mexico City, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00fal","family":"Valverde","sequence":"additional","affiliation":[{"name":"Department of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Nephrology and Mineral Metabolism Research Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindal","family":"Vargas","sequence":"additional","affiliation":[{"name":"Nephrology and Mineral Metabolism Research Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Pati\u00f1o","sequence":"additional","affiliation":[{"name":"Nephrology and Mineral Metabolism Research Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"P\u00e9rez-Villalva","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico; and"},{"name":"Department of Nephrology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Ortega-Trejo","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico; and"},{"name":"Department of Nephrology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatan","family":"Barrera-Chimal","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico; and"},{"name":"Department of Nephrology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma A.","family":"Bobadilla","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico; and"},{"name":"Department of Nephrology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,5,23]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1056\/NEJMoa020009","article-title":"The natural history of chronic allograft nephropathy.","volume":"349","author":"Nankivell","year":"2003","journal-title":"N Engl J Med"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/01.mnh.0000444811.26884.2d","article-title":"Chronic allograft nephropathy or interstitial fibrosis and tubular atrophy: What is in a name?","volume":"23","author":"Haas","year":"2014","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B3-20230813","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1600-6143.2010.03312.x","article-title":"The histology of solitary renal allografts at 1 and 5 years after transplantation.","volume":"11","author":"Stegall","year":"2011","journal-title":"Am J Transplant"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3109\/0886022X.2015.1024563","article-title":"The role of renin-angiotensin system in the chronic allograft nephropathy: An immunohistochemical study.","volume":"37","author":"Viero","year":"2015","journal-title":"Ren Fail"},{"issue":"1A Suppl","key":"B5-20230813","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1016\/S0041-1345(00)00807-1","article-title":"Nephrotoxicity of calcineurin inhibitors: New therapeutic approaches.","volume":"32","author":"Abramowicz","year":"2000","journal-title":"Transplant 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(Berl)"},{"key":"B12-20230813","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1161\/HYPERTENSIONAHA.107.102640","article-title":"Osteopontin in rat renal fibroblasts: Functional properties and transcriptional regulation by aldosterone.","volume":"51","author":"Irita","year":"2008","journal-title":"Hypertension"},{"key":"B13-20230813","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.1096\/fj.15-271734","article-title":"Excess aldosterone is a critical danger signal for inflammasome activation in the development of renal fibrosis in mice.","volume":"29","author":"Kadoya","year":"2015","journal-title":"FASEB J"},{"key":"B14-20230813","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000225379","article-title":"Direct aldosterone action as a profibrotic factor via ROS-mediated SGK1 in peritoneal fibroblasts.","volume":"32","author":"Yamahara","year":"2009","journal-title":"Kidney Blood Press 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