Chandu Avinash, Arana Carolt, Díaz-García Juan Daniel, Cozzolino Mario, Ciceri Paola, Torregrosa José-Vicente
Nephrology and Renal Transplant Department, Hospital Clínic, 08036 Barcelona, Spain.
Department of Health Sciences, University of Milan, 20142 Milan, Italy.
Toxins (Basel). 2025 Jun 12;17(6):297. doi: 10.3390/toxins17060297.
In patients with chronic kidney disease (CKD), cardiovascular events (CVA) are the main cause of morbidity and mortality. Vascular calcification, linked to bone mineral metabolism disorders such as elevated serum phosphate, parathyroid hormone (PTH), and FGF23, well-known uremic toxins, aggravate this risk. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR), a G protein-coupled receptor that regulates PTH secretion and synthesis in response to changes in extracellular calcium in the parathyroid glands. Through direct and indirect mechanisms, they have demonstrated their efficacy in reducing the progression of vascular, valvular, and soft tissue calcification in experimental studies. Although clinical studies in dialysis patients did not achieve statistical significance in their primary objectives, positive results in subgroup analyses suggest that the lack of significance may be attributable to the short follow-up period. This finding highlights the need to consider early treatment strategies, especially in advanced stages of chronic kidney disease, to more effectively address the progression of vascular calcification through serum uremic toxins control.
在慢性肾脏病(CKD)患者中,心血管事件(CVA)是发病和死亡的主要原因。血管钙化与骨矿物质代谢紊乱相关,如血清磷酸盐、甲状旁腺激素(PTH)升高以及成纤维细胞生长因子23(FGF23)(众所周知的尿毒症毒素),会加剧这种风险。拟钙剂是钙敏感受体(CaSR)的变构激活剂,CaSR是一种G蛋白偶联受体,可根据甲状旁腺细胞外钙的变化调节PTH的分泌和合成。在实验研究中,通过直接和间接机制,它们已证明在减少血管、瓣膜和软组织钙化进展方面的有效性。尽管针对透析患者的临床研究在其主要目标上未达到统计学意义,但亚组分析中的阳性结果表明,缺乏显著性可能归因于随访期较短。这一发现凸显了需要考虑早期治疗策略,尤其是在慢性肾脏病的晚期阶段,以通过控制血清尿毒症毒素更有效地应对血管钙化的进展。