{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:48:10Z","timestamp":1761536890559,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Erythropoiesis\u2010stimulating agents (ESAs) may be associated with inhibition of urinary protein; however, information from large\u2010scale real\u2010world clinical settings is insufficient. We aimed to investigate whether darbepoetin alfa (DA) was associated with reduced proteinuria in patients with chronic kidney disease (CKD) using data from the \u2018oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis\u2010stimulating agents, darbepoetiN alfa (BRIGHTEN)\u2019 observational study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 1161 patients treated with DA were analysed, including 307 with diabetic kidney disease (DKD), 286 with nephrosclerosis and 285 with chronic glomerulonephritis. We estimated the nonlinear relationship between DA dose and change in urinary protein\u2010creatinine ratio (UPCR) at 12\u2009weeks using a spline curve. We also explored the potential clinical relevance of the association between higher DA doses and changes in proteinuria by comparing the slope of DA dosage and UPCR reduction between patients with high and low ESA resistance, which is associated with CKD prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The UPCR appeared to decrease as the DA dose exceeded 50\u2009\u03bcg, particularly in the DKD group. The slopes of DA dosage and UPCR reduction significantly differed (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009) between the high\u2010 and low\u2010ESA resistance groups, especially in patients with DKD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). This difference was maintained after adjustment for factors such as the presence or absence of renin\u2010angiotensin\u2010aldosterone system inhibitors and blood pressure variability during the study period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DA administration was associated with reduced proteinuria in a dose\u2010dependent manner, particularly in patients with DKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.70140","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:09:30Z","timestamp":1761217770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential Association Between Darbepoetin Alfa Administration and Reduced Proteinuria in Real\u2010World Clinical Practice: A Post Hoc Analysis of the\n                    <scp>BRIGHTEN<\/scp>\n                    Study"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3741-5672","authenticated-orcid":false,"given":"Shuma","family":"Hirashio","sequence":"first","affiliation":[{"name":"Department of Nephrology National Hospital Organization Hiroshima\u2010Nishi Medical Center  Hiroshima Japan"},{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-9964","authenticated-orcid":false,"given":"Takao","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Kagimura","sequence":"additional","affiliation":[{"name":"Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiei","family":"Narita","sequence":"additional","affiliation":[{"name":"Division of Clinical Nephrology and Rheumatology Niigata University Graduate School of Medical and Dental Sciences  Niigata 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