{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T22:53:56Z","timestamp":1794092036833,"version":"4.8.0"},"reference-count":126,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CSL Vifor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Uremic secondary hyperparathyroidism (SHP) refers to the biochemical abnormalities that characterize CKD-MBD. However, historically parathyroid hormone (PTH) is identified as the key culprit hormone and the essential biomarker of secondary hyperparathyroidism. SHP represents the adaptive response to several mineral abnormalities that initiate and maintain increased PTH secretion through classical mineral derangements and more recently elucidated hormonal dysregulations. Among classic factors involved in the pathogenesis of SHP, phosphate, calcium, and calcitriol have a prominent role. The discovery of new pathogenetic factors involved in the development of SHP (and the eventual CKD-MBD) including fibroblast growth factor-23 (FGF23) and klotho provides new hypothesis and perspectives to our understanding of this complex metabolic disturbance. Recently more than serum phosphate a critical role in regulating FGF23 synthesis and the progression of CKD is ascribed to phosphate pool, reflected by production of glycerol-3-phosphate and the formation of excessive CPP-2. Finally, also skeletal resistance to PTH action, due to dysregulation of the Wnt\u2013\u03b2-catenin system and intestinal dysbiosis, affecting the PTH actions on bone are causal factor of SHP. Identifying all the actors at play is mandatory to allow the most precise therapeutic prescription in the individual patient. This paper aims to review, in particular, the pathophysiology of SHP, which is essential to envisage the eventual therapeutic options for the associated MBD.<\/jats:p>","DOI":"10.1093\/ckj\/sfae423","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T15:33:44Z","timestamp":1734536024000},"page":"i15-i26","source":"Crossref","is-referenced-by-count":22,"title":["Pathophysiology and therapies of CKD-associated secondary hyperparathyroidism"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3071-1893","authenticated-orcid":false,"given":"Sandro","family":"Mazzaferro","sequence":"first","affiliation":[{"name":"Department of Translation and Precision Medicine, Sapienza University of Rome , Rome ,","place":["Italy"]},{"name":"Nephrology Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I Hospital , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Tartaglione","sequence":"additional","affiliation":[{"name":"UOSD Dialysis, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I Hospital , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-8258","authenticated-orcid":false,"given":"Martine","family":"Cohen-Solal","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Reference Center for Rare Bone Disease in Adults, Lariboisi\u00e8re Hospital , APHP. Nord ,","place":["France"]},{"name":"Inserm U1132, BIOSCAR, Paris, Universit\u00e9 Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Hoang Tran","sequence":"additional","affiliation":[{"name":"NTT Hi-Tech Institute, Nguyen Tat Thanh University , Ho Chi Minh City ,","place":["Vietnam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I Hospital , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silverio","family":"Rotondi","sequence":"additional","affiliation":[{"name":"Department of Translation and Precision Medicine, Sapienza University of Rome , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6757-1906","authenticated-orcid":false,"given":"Pablo","family":"Ure\u00f1a Torres","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Dialysis, AURA Saint Ouen-sur-Seine , Paris ,","place":["France"]},{"name":"Department of Renal Physiology, Necker Hospital, University of Paris Descartes , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"2025031300030386500_bib1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1038\/sj.ki.5000414","article-title":"Kidney Disease: Improving Global Outcomes (KDIGO). 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