{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:32:34Z","timestamp":1793287954817,"version":"4.5.0"},"reference-count":55,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by progressive cyst development and renal dysfunction. While thyroid hormones (THs) are known to regulate key pathways in various kidney diseases, their role in ADPKD pathobiology and therapeutic potential remains unexplored. Here, we aimed to elucidate the role of THs in ADPKD and evaluate whether their pharmacological modulation could serve as a therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Patient-derived renal epithelial cells were used to engineer 3D polycystic tubules and to test the anti-cystogenic\u00a0effects of THs and their analogs. The therapeutic efficacy of thyroxine (T4) in reducing cyst formation and delaying disease progression was assessed\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      using PCK rats, an animal model of ADPKD. Lastly, serum THs levels were measured in 90 ADPKD patients enrolled in the REORIENTED clinical study and correlated with estimated glomerular filtration rate to explore their clinical relevance (Clinical Trial Gov NCT 05646420).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Mechanistically, thyroxine inhibits cyst growth by modulating proliferative, metabolic and ferroptotic pathways through \u03b1v\u03b23 integrin binding. In PCK rats, an animal model of ADPKD, T4 administration decreased kidney weight and significantly reduced macrocystic area (%, Vehicle 9.255 \u00b1 2.654 vs. T4 1.945 \u00b1 0.850,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.05). Clinical data from ADPKD patients showed that altered TH serum levels correlate with disease severity: in the overall population of the study reverse triiodothyronine (rT3, a T3\u2032s metabolite) levels inversely correlate with renal function\u00a0(\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      = 0.159,\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      = \u22120.397,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001), while free triiodothyronine (fT3) levels show a positive correlation (\n                      <jats:italic toggle=\"yes\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      = 0.110,\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      = 0.332,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study reveals that THs contribute to ADPKD progression and identifies them as potential prognostic and therapeutic agents. By modulating multiple pathogenic pathways, THs may offer a novel, multi-targeted approach to reduce cyst growth and preserve renal function. These findings further support the development of personalized, hormone-based treatments and more refined stratification in the clinical management of ADPKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256261460200","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T17:14:36Z","timestamp":1781543676000},"page":"840-852","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thyroid Hormones Exhibit Promising Prognostic and Therapeutic Potential in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1177","volume":"36","author":[{"given":"Angelo Michele","family":"Lavecchia","sequence":"first","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche 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