{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:41:43Z","timestamp":1773121303702,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nephrol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Renal failure associated aortic valve calcification (AVC) is the result of hyperphosphatemia and hyperparathyroidism. Calcimimetics is an effective tool for management of secondary hyperparathyroidism. Our goal was to evaluate the effect of the medical intervention with calcimimetic R568 on the AVC process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The experimental design consisted of administering a uremia-inducing phosphate-enriched diet to rats for six weeks. Rats received a daily R568 injection at different times. Biochemical analysis demonstrated increased urea (34.72 \u00b1 3.57 <jats:italic>vs<\/jats:italic>. 5.18 \u00b1 0.15 mmol\/L, <jats:italic>p<\/jats:italic>&amp;lt;0.05) and creatinine (293.93 \u00b1 79.6 <jats:italic>vs<\/jats:italic>. 12.82 \u00b1 1.56 \u00b5mol\/L, <jats:italic>p<\/jats:italic>&amp;lt;0.05). R568 treatment markedly reduced parathyroid hormone (PTH) levels in both treated groups (192.63 \u00b1 26.85, 301.23 \u00b1 101.79 <jats:italic>vs<\/jats:italic>. 3570 \u00b1 986.63 pg\/mL, <jats:italic>p<\/jats:italic>&amp;lt;0.05), with no impact on serum calcium and phosphate. von Kossa staining showed increase in AVC in uremic rats compared to control (1409 \u00b1 159.5 <jats:italic>vs<\/jats:italic>. 27.33 \u00b1 25.83, <jats:italic>p<\/jats:italic>&amp;lt;0.05). AVC was not affected by R568 in both groups (3343 \u00b1 2462, 1593 \u00b1 792 <jats:italic>vs<\/jats:italic>. 1409 \u00b1 159.5, NS). Similarly, the inflammatory marker CD68 was elevated in uremic rats (15592 \u00b1 3792 <jats:italic>vs<\/jats:italic>. 181.8 \u00b1 15.29, <jats:italic>p<\/jats:italic>&amp;lt;0.01), and was not influenced by R568 treatment (8453 \u00b1 818.5, 9318 \u00b1 2232 <jats:italic>vs<\/jats:italic>. 15592 \u00b1 3792, NS). Runt-related transcription factor 2 (Runx2), the regulator of osteoblast differentiation, was upregulated in uremic rats (23186 \u00b1 9226 <jats:italic>vs<\/jats:italic>. 3184 \u00b1 2495), that accompanied by elevated levels of Osteopontin (158395 \u00b1 45911 <jats:italic>vs<\/jats:italic>. 237.7 \u00b1 81.5, <jats:italic>p<\/jats:italic>&amp;lt;0.05) and Osteocalcin (22203 \u00b1 8525 <jats:italic>vs<\/jats:italic>. 489.7 \u00b1 200.6, <jats:italic>p<\/jats:italic>&amp;lt;0.05). R568 had no impact on osteoblastic markers (Runx2: 21743 \u00b1 3193, 23004 \u00b1 10871 <jats:italic>vs<\/jats:italic>. 23186 \u00b1 9226, NS; osteopontin: 57680 \u00b1 19522, 137116 \u00b1 60103 <jats:italic>vs<\/jats:italic>. 158395 \u00b1 45911, NS; osteocalcin: 10496 \u00b1 5429, 8522 \u00b1 5031 <jats:italic>vs<\/jats:italic>. 22203 \u00b1 8525, NS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In an adenine-induced uremic rat model, we showed that short-term R568 therapy had no effect on AVC. Treatment with R568 decreased PTH levels but had no effect on high phosphate levels. Regression of AVC necessitates not only a decrease in PTH levels, but also a decline in phosphate levels. To achieve improved outcomes, it is advisable to consider administering a combination of R568 with other medications, such as calcium supplements or phosphate binders. Additional studies are required for further evaluation of the potential treatment of chronic kidney disease (CKD)-associated AVC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneph.2024.1385705","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T10:26:03Z","timestamp":1722939963000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Short-term therapy with R568 ameliorated secondary hyperparathyroidism but does not prevent aortic valve calcification in uremic 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