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ORIGINAL RESEARCH article

Front. Nephrol.
Sec. Cardionephrology
Volume 4 - 2024 | doi: 10.3389/fneph.2024.1385705

Short-Term Therapy with R568 Ameliorated secondary Hyperparathyroidism but Does not Prevent Aortic Valve Calcification in Uremic Rats

Provisionally accepted
Asmahan Abu-Snieneh Asmahan Abu-Snieneh 1Irina Gurt Irina Gurt 2Suzan Abedat Suzan Abedat 1Chaim Lotan Chaim Lotan 1Michael Glikson Michael Glikson 2Mony Shuvy Mony Shuvy 2*
  • 1 Department of Cardiology, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
  • 2 Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Jerusalem, Israel

The final, formatted version of the article will be published soon.

    Introduction: 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.The experimental design consisted of administering a uremiainducing phosphate-enriched diet to rats for six weeks. Rats received a daily R568 injection at different times. Biochemical analysis demonstrated increased urea (34.72 ± 3.57 vs. 5.18 ± 0.15 mmol/L, p<0.05) and creatinine (293.93 ± 79.6 vs. 12.82 ± 1.56 µmol/L, p<0.05). R568 treatment markedly reduced parathyroid hormone (PTH) levels in both treated groups (192.63 ± 26.85, 301.23 ± 101.79 vs. 3570 ±986.63 pg/mL, p<0.05), with no impact on serum calcium and phosphate. von Kossa staining showed increase in AVC in uremic rats compared to control (1409±159.5 vs. 27.33±25.83, p<0.05). AVC was not affected by R568 in both groups (3343±2462, 1593±792 vs. 1409±159.5, NS). Similarly, the inflammatory marker CD68 was elevated in uremic rats (15592±3792 vs. 181.8±15.29, p<0.01), and was not influenced by R568 treatment (8453±818.5, 9318±2232 vs. 15592±3792, NS). Runt-related transcription factor 2 (Runx2), the regulator of osteoblast differentiation, was upregulated in uremic rats (23186±9226 vs. 3184±2495), that accompanied by elevated levels of Osteopontin (158395±45911 vs. 237.7±81.5, p<0.05) and Osteocalcin (22203±8525 vs.

    Keywords: Aortic valve calcification, Chronic Kidney Disease, Phosphate, R568, animal model

    Received: 25 Feb 2024; Accepted: 19 Jul 2024.

    Copyright: © 2024 Abu-Snieneh, Gurt, Abedat, Lotan, Glikson and Shuvy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mony Shuvy, Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, 9103102, Jerusalem, Israel

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