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Parikh,<sup>3</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-6"> Taryn G. Vosters,<sup>4</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-7"> Irene GM van Valkengoed,<sup>4</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-8"> Merle M. Krebber,<sup>5</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-9"> Daan J. Touw,<sup>6</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-10"> Martin den Heijer,<sup>1</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-11"> Petter Bjornstad,<sup>2</sup> </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-12"> Dani毛l Raalte,<sup>7</sup> and </a> <a class="author-affiliation show-more" href="javascript:void(0);" data-dropdown="author-affiliation-13"> Natalie J. Nokoff<sup>8</sup> </a> </h4> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-0"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p class="affiliations"><sup>3</sup>Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, United States of America</p><p class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by van Eeghen, S. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Sarah A.%22+author.last_name%3A%22van Eeghen%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=van Eeghen+S[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AS+van Eeghen%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-1"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p class="affiliations"><sup>3</sup>Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, United States of America</p><p class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Pyle, L. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Laura%22+author.last_name%3A%22Pyle%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Pyle+L[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AL+Pyle%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-2"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p class="affiliations"><sup>3</sup>Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, United States of America</p><p class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Narongkiatikhun, P. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Phoom%22+author.last_name%3A%22Narongkiatikhun%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Narongkiatikhun+P[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AP+Narongkiatikhun%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-3"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p class="affiliations"><sup>3</sup>Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, United States of America</p><p class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Choi, Y. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Ye Ji%22+author.last_name%3A%22Choi%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Choi+Y[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AY+Choi%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-4"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p 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Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Parikh, C. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Chirag R.%22+author.last_name%3A%22Parikh%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Parikh+C[au]&dispmax=50" >PubMed </a> | <a target="_blank" 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Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Vosters, T. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Taryn G.%22+author.last_name%3A%22Vosters%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Vosters+T[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AT+Vosters%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-7"> <p><p 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class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Touw, D. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Daan J.%22+author.last_name%3A%22Touw%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Touw+D[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AD+Touw%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-10"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p class="affiliations"><sup>3</sup>Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, United States of America</p><p class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, 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class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Bjornstad, P. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Petter%22+author.last_name%3A%22Bjornstad%22&search_type=advanced" >JCI </a> | <a target="_blank" 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class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Raalte, D. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Dani毛l%22+author.last_name%3A%22Raalte%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Raalte+D[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AD+Raalte%22" >Google Scholar </a> </p> </div> <div class="f-dropdown content large" data-dropdown-content id="author-affiliation-13"> <p><p class="affiliations"><sup>1</sup>Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>2</sup>Division of Endocrinology, University of Washington School of Medicine, Seattle, United States of America</p><p class="affiliations"><sup>3</sup>Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, United States of America</p><p class="affiliations"><sup>4</sup>Department of Public and Occupational Health, Universiteit van Amsterdam, Amsterdam, Netherlands</p><p class="affiliations"><sup>5</sup>Department of Nephrology and Hypertension, University Medical Center, Utrecht, Netherlands</p><p class="affiliations"><sup>6</sup>Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen, Netherlands</p><p class="affiliations"><sup>7</sup>Department of Internal Medicine, Endocrinology and Metabolism, Amsterdam UMC, Amsterdam, Netherlands</p><p class="affiliations"><sup>8</sup>Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America</p></p> <p> Find articles by Nokoff, N. in: <a target="_blank" href="/search/results?q=author.first_name%3A%22Natalie J.%22+author.last_name%3A%22Nokoff%22&search_type=advanced" >JCI </a> | <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pubmed&term=Nokoff+N[au]&dispmax=50" >PubMed </a> | <a target="_blank" href="http://scholar.google.com/scholar?q=%22author%3AN+Nokoff%22" >Google Scholar </a> </p> </div> <p class='publication_date'> Published April 7, 2025 - <a class='show-more' data-dropdown='full-publication-dropdown' href='javascript:void(0);'> More info </a> </p> <div class='f-dropdown content large' data-dropdown-content='' id='full-publication-dropdown'> <div class='copyright'> <i> J Clin Invest. </i> <a href="https://doi.org/10.1172/JCI190850">https://doi.org/10.1172/JCI190850</a>. <br> Copyright 漏 2025, van Eeghen et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. </div> <div class='publication_date'> Published April 7, 2025 - <a href="#version_history">Version history</a> </div> </div> <a href="/articles/view/190850/pdf">View PDF <img class="article-tools-icon" src="//dm5migu4zj3pb.cloudfront.net/images/adobe_pdf_file_icon.png" /></a> <div class="content_well"> <a class="in-page" name="ABS"></a><dl class="article-section" data-accordion=""><dd class="accordion-navigation active"> <a href="#section-abstract"><span class="toggle-icon"></span><span class="section-title">Abstract</span></a><div id="section-abstract" class="content active"><p>Background: 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. Methods: This prospective, observational study included individuals initiating feminizing (estradiol and antiandrogens; n=23) or masculinizing (testosterone; n=21) therapy. Baseline and three-month assessments included mGFR (Iohexol clearance), kidney perfusion (para-aminohippuric acid clearance), tubular injury biomarkers, and plasma proteomics. Results: During feminizing therapy, mGFR and kidney perfusion increased (+3.6% and +9.1%, respectively; p<0.05), without increased glomerular pressure. Tubular injury biomarkers, including urine neutrophil gelatinase-associated lipocalin, EGF, monocyte chemoattractant protein-1, and chitinase 3-like protein 1 (YKL-40), decreased significantly (-53%, -42%, -45%, and -58%, respectively). During masculinizing therapy, mGFR and kidney perfusion remained unchanged, but urine YKL-40 and plasma TNFR-1 increased (+134% and +8%, respectively; p<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). Conclusion: 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.</p></div> </dd></dl> <a class="in-page" name="sd"></a><dl class="article-section" data-accordion=""><dd class="accordion-navigation active"> <a href="#supplemental-material"><span class="toggle-icon"></span><span class="section-title">Supplemental material</span></a><div id="supplemental-material" class="content active"> <p><a href="/articles/view/190850/sd/1"> View </a></p> <p><a href="/articles/view/190850/sd/2"> View Appendix S14A</a></p> <p><a href="/articles/view/190850/sd/3"> View Appendix S14B</a></p> <p><a href="/articles/view/190850/sd/4"> View Appendix S14C</a></p> <p><a href="/articles/view/190850/sd/5"> View Appendix S14D</a></p> <p><a href="/articles/view/190850/sd/6"> View Appendix S14EFGH</a></p> <p><a href="/articles/view/190850/sd/7"> View Appendix S14I</a></p> <p><a href="/articles/view/190850/sd/8"> View Appendix S14J</a></p> <p><a href="/articles/view/190850/sd/9"> View Figure 1 revised</a></p> <p><a href="/articles/view/190850/sd/10"> View Figure 2 revised</a></p> <p><a href="/articles/view/190850/sd/11"> View Figure 4 revised</a></p> </div> </dd></dl> </div> <dl class='article-section' data-accordion> <dd class='accordion-navigation active'> <a href='#version_history'> <span class='toggle-icon'></span> <span class='section-title'>Version history</span> </a> <div class='content active' id='version_history'> <ul> <li> Version 1 (April 7, 2025): In-Press Preview </li> </ul> </div> </dd> </dl> </div> <div class="large-3 columns show-for-large-up"> <div id='sidebar-container'> <div id='sidebar'> <div class='non-sticky-content'> <h4 class='subheader'>Article tools</h4> <ul class='side-nav' id='article-tools'> <li class='hide-for-small'> <a href="/articles/view/190850/pdf">View PDF <img class="article-tools-icon" src="//dm5migu4zj3pb.cloudfront.net/images/adobe_pdf_file_icon.png" /></a> </li> <li><a href="/articles/view/190850/cite">Download citation information</a></li> <li><a href="/eletters/submit/190850">Send a comment</a></li> <li><a href="/kiosks/terms">Terms of use</a></li> <li><a href="/kiosks/publish/abbreviations">Standard abbreviations</a></li> <li><a href="/feedback?reference=190850">Need help? 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