Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Oviedo, Spain.
Laboratory of Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
Nephrol Dial Transplant. 2021 Apr 26;36(5):793-803. doi: 10.1093/ndt/gfaa373.
In chronic kidney disease, the activation of the renin-angiotensin-aldosterone system (RAAS) and renal inflammation stimulates renal fibrosis and the progression to end-stage renal disease. The low levels of vitamin D receptor (VDR) and its activators (VDRAs) contribute to worsen secondary hyperparathyroidism and renal fibrosis.
The 7/8 nephrectomy model of experimental chronic renal failure (CRF) was used to examine the anti-fibrotic effects of treatment with two VDRAs, paricalcitol and calcitriol, at equivalent doses (3/1 dose ratio) during 4 weeks.
CRF increased the activation of the RAAS, renal inflammation and interstitial fibrosis. Paricalcitol treatment reduced renal collagen I and renal interstitial fibrosis by decreasing the activation of the RAAS through renal changes in renin, angiotensin receptor 1 (ATR1) and ATR2 mRNAs levels and renal inflammation by decreasing renal inflammatory leucocytes (CD45), a desintegrin and metaloproteinase mRNA, transforming growth factor beta mRNA and protein, and maintaining E-cadherin mRNA levels. Calcitriol showed similar trends without significant changes in most of these biomarkers.
Paricalcitol effectively attenuated the renal interstitial fibrosis induced by CRF through a combination of inhibitory actions on the RAAS, inflammation and epithelial/mesenchymal transition.
在慢性肾脏病中，肾素-血管紧张素-醛固酮系统（RAAS）的激活和肾脏炎症会刺激肾纤维化并导致终末期肾病进展。维生素 D 受体（VDR）及其激活剂（VDRAs）水平降低会加重继发性甲状旁腺功能亢进和肾纤维化。
使用 7/8 肾切除术模型研究了两种 VDRAs，帕立骨化醇和骨化三醇，以等效剂量（3/1 剂量比）治疗 4 周对实验性慢性肾衰竭（CRF）的抗纤维化作用。
CRF 增加了 RAAS 的激活、肾脏炎症和间质纤维化。帕立骨化醇通过降低肾素、血管紧张素受体 1（ATR1）和 ATR2 mRNA 水平以及肾炎症中白细胞（CD45）、去整合素和金属蛋白酶 mRNA、转化生长因子β mRNA 和蛋白的减少，减少了肾胶原 I 和肾间质纤维化，从而降低了 RAAS 的激活，并通过维持 E-钙粘蛋白 mRNA 水平来减少肾脏炎症。骨化三醇显示出类似的趋势，但大多数这些生物标志物没有显著变化。
帕立骨化醇通过对 RAAS、炎症和上皮/间充质转化的抑制作用，有效减轻了 CRF 引起的肾间质纤维化。
