{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:10:45Z","timestamp":1791274245406,"version":"4.1.0"},"reference-count":90,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":37,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Colorado Clinical and Translational Sciences Institute MicroGrant and CO-Pilot award","award":["NIH\/NCATS TR002535"],"award-info":[{"award-number":["NIH\/NCATS TR002535"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Men with chronic kidney disease (CKD) experience faster kidney function decline than women. Studies in individuals undergoing sex hormone therapy suggest a role for sex hormones, as estimated glomerular filtration rate (eGFR) increases with feminizing therapy and decreases with masculinizing therapy. However, effects on measured GFR (mGFR), glomerular and tubular function, and involved molecular mechanisms remain unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      This prospective, observational study included individuals initiating feminizing (estradiol and antiandrogens;\n                      <jats:italic>n<\/jats:italic>\n                      = 23) or masculinizing (testosterone;\n                      <jats:italic>n<\/jats:italic>\n                      = 21) therapy. Baseline and 3-month assessments included mGFR (iohexol clearance), kidney perfusion (para-aminohippuric acid clearance), tubular injury biomarkers, and plasma proteomics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      During feminizing therapy, mGFR and kidney perfusion increased (+3.6% and +9.1%, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) without increased glomerular pressure. Tubular injury biomarkers, including urine neutrophil gelatinase-associated lipocalin, epidermal growth factor (EGF), monocyte chemoattractant protein-1, and chitinase 3-like protein 1 (YKL-40), decreased significantly (\u201353%, \u201342%, \u201345%, and \u201358%, respectively). During masculinizing therapy, mGFR and kidney perfusion remained unchanged, but urine YKL-40 and plasma tumor necrosis factor receptor 1 (TNFR-1) increased (+134% and +8%, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Proteomic analysis revealed differential expression of 49 proteins during feminizing and 356 proteins during masculinizing therapy. Many kidney-protective proteins were positively associated with estradiol and negatively associated with testosterone, including proteins involved in endothelial function (SFRP4, SOD3), inflammation reduction (TSG-6), and maintaining kidney tissue structure (agrin).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Sex hormones influence kidney physiology, with estradiol showing protective effects on glomerular and tubular function, while testosterone predominantly exerts opposing effects. These findings emphasize the role of sex hormones in sexual dimorphism observed in kidney function and physiology and suggest new approaches for sex-specific precision medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>Dutch Trial Register (ID: NL9517); ClinicalTrials.gov (ID: NCT04482920).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci190850","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T15:48:17Z","timestamp":1744040897000},"source":"Crossref","is-referenced-by-count":31,"title":["Unveiling mechanisms underlying kidney function changes during sex hormone therapy"],"prefix":"10.1172","volume":"135","author":[{"given":"Sarah A.","family":"van Eeghen","sequence":"first","affiliation":[{"name":"Center of Expertise on Gender Dysphoria, Department of Internal Medicine, Amsterdam UMC, Location VU University, Amsterdam, Netherlands."},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands."},{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Location VU University, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pyle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA."},{"name":"Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoom","family":"Narongkiatikhun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA."},{"name":"Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Ji","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA."},{"name":"Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6054-411X","authenticated-orcid":true,"given":"Wassim","family":"Obeid","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-7385","authenticated-orcid":true,"given":"Chirag R.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn G.","family":"Vosters","sequence":"additional","affiliation":[{"name":"Department of Public and Occupational Health, Amsterdam University Medical Centre, Universiteit van Amsterdam, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene G.M.","family":"van Valkengoed","sequence":"additional","affiliation":[{"name":"Department of Public and Occupational Health, Amsterdam University Medical Centre, Universiteit van Amsterdam, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merle M.","family":"Krebber","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"den Heijer","sequence":"additional","affiliation":[{"name":"Center of Expertise on Gender Dysphoria, Department of Internal Medicine, Amsterdam UMC, Location VU University, Amsterdam, Netherlands."},{"name":"Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands."},{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Location VU University, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petter","family":"Bjornstad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of 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