Conclusion
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.
Results
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 ± 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. 489.7 ± 200.6, p<0.05). R568 had no impact on osteoblastic markers (Runx2: 21743 ± 3193, 23004 ± 10871 vs. 23186 ± 9226, NS; osteopontin: 57680 ± 19522, 137116 ± 60103 vs. 158395 ± 45911, NS; osteocalcin: 10496 ± 5429, 8522 ± 5031 vs. 22203 ± 8525, NS).