Department of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China.
Ren Fail. 2023 Dec;45(1):2228920. doi: 10.1080/0886022X.2023.2228920.
Ectopic calcification (EC) involves multiple organ systems in chronic kidney disease (CKD). Previous CKD-animal models primarily focused on a certain histological abnormality but did not show the correlation with calcified development among various tissues. This study compared calcified deposition in various tissues during CKD progression in mice.
Male 8-week-old C57BL/6J mice were randomly allocated to the seven groups: a basic, adenine, high-phosphorus, or adenine and high-phosphorus diet for 12-16 weeks (Ctl16, A12, P16, or AP16, respectively); an adenine diet for 4-6 weeks; and a high-phosphorus or adenine and high-phosphorus diet for 10-12 weeks (A6 + P10, A4 + P12, or A4 + AP12, respectively).
Compared to the Ctl16 mice, the P16 mice only displayed a slight abnormality in serum calcium and phosphorus; the A12 mice had the most serious kidney impairment; the A4 + P12 and A6 + P10 mice had similar conditions of CKD, mineral abnormalities, and mild calcification in the kidney and aortic valves; the A4 + AP12 and AP16 groups had severe kidney impairment, mineral abnormalities and calcification in the kidneys, aortic valves and aortas. Furthermore, calcium-phosphate particles were deposited not only in the tubulointerstitial compartment but in the glomerular and tubular basement membrane. The elemental composition of EC in various tissues matched the calcification of human cardiovascular tissue as determined by energy dispersive spectroscopy.
The severity of CKD was unparalleled with the progression of mineral metabolism disorder and EC. Calcification was closely related in different tissues and observed in the glomerular and tubular basement membranes.
慢性肾脏病（CKD）患者的异位钙化（EC）涉及多个器官系统。之前的 CKD 动物模型主要集中在某种组织学异常上，但并未显示出与各种组织之间钙化发展的相关性。本研究比较了 CKD 进展过程中不同组织中的钙化沉积。
雄性 8 周龄 C57BL/6J 小鼠被随机分配到七个组：基础组、腺嘌呤组、高磷组或腺嘌呤和高磷组喂养 12-16 周（分别为 Ctl16、A12、P16 和 AP16）；腺嘌呤喂养 4-6 周；以及高磷或腺嘌呤和高磷喂养 10-12 周（分别为 A6+P10、A4+P12 和 A4+AP12）。
与 Ctl16 小鼠相比，P16 小鼠仅表现出血清钙磷轻度异常；A12 小鼠肾脏损伤最严重；A4+P12 和 A6+P10 小鼠具有相似的 CKD 状态、矿物质异常和肾脏、主动脉瓣的轻度钙化；A4+AP12 和 AP16 组具有严重的肾脏损伤、矿物质异常和肾脏、主动脉瓣和主动脉的钙化。此外，钙磷颗粒不仅沉积在肾小管间质区，还沉积在肾小球和肾小管基底膜。通过能量色散光谱分析，发现各组织中 EC 的元素组成与心血管组织的钙化相匹配。
CKD 的严重程度与矿物质代谢紊乱和 EC 的进展不成比例。钙化在不同组织中密切相关，并在肾小球和肾小管基底膜中观察到。
