Kawamura J, Nonomura M, Okada Y, Yoshida O, Takashima M, Itokawa Y
Hinyokika Kiyo. 1985 May;31(5):749-62.
Combination of 1 alpha(OH) D3(vit D) and ethylene glycol induced renal or ureteral stones or both consisting of calcium oxalate in male Wistar rats. This study investigates the effect of EHDP on calcium oxalate stone using the rat model. EHDP reduced the frequency of renal stone and calcium content in the kidney, and reduced the size of the stones in the renal pelvis and ureter. EHDP biochemically ameliorated renal injury induced by vit D and ethylene glycol. EHDP suppressed urinary excretion of calcium even though serum calcium slightly increased. EHDP had a phosphaturic action. EHDP elevated urinary excretion of magnesium. However, the severity of hypermagnesuria decreased in the rat which was not given EHDP concomitantly. Although EHDP slightly elevated urinary excretion of oxalate in the control rat, it did not affect the high level of urinary oxalate in the vit D/ethylene glycol rat. EHDP did not produce any histological change in the kidney or femoral bone. These data indicate that EHDP can suppress renal stone formation in the vit D/ethylene glycol rat. It is speculated that firstly, EHDP may physicochemically inhibit stone formation in the process of nidus, aggregation and crystal growth of calcium oxalate, under the supersaturated condition of calcium oxalate in the urine, and secondly, EHDP may endocrinologically inhibit production of 1,25 (OH)2 vit D in the kidney or inhibit 1, 25 (OH)2 vit D-mediated intestinal calcium absorption. It is suggested that in order to prevent stone recurrence, EHDP may be clinically applied not only to calcium phosphate stones but also to calcium oxalate stones and hypercalciuria mediated by an active form of vitamin D.
1α(OH)D3（维生素D）与乙二醇联合可诱导雄性Wistar大鼠形成肾或输尿管结石或两者皆有，结石成分为草酸钙。本研究使用大鼠模型探究依替膦酸二钠（EHDP）对草酸钙结石的影响。EHDP降低了肾结石的发生率以及肾脏中的钙含量，并减小了肾盂和输尿管中结石的尺寸。EHDP在生化方面改善了由维生素D和乙二醇诱导的肾损伤。尽管血清钙略有升高，但EHDP抑制了尿钙排泄。EHDP具有促尿磷排泄作用。EHDP增加了尿镁排泄。然而，未同时给予EHDP的大鼠高镁尿症的严重程度有所降低。尽管EHDP在对照大鼠中略微增加了草酸排泄，但它并未影响维生素D/乙二醇处理大鼠中高水平的尿草酸。EHDP未在肾脏或股骨中产生任何组织学变化。这些数据表明EHDP可抑制维生素D/乙二醇处理大鼠中的肾结石形成。据推测，首先，在尿液中草酸钙处于过饱和状态的情况下，EHDP可能在草酸钙的成核、聚集和晶体生长过程中通过物理化学方式抑制结石形成；其次，EHDP可能在内分泌方面抑制肾脏中1,25(OH)2维生素D的产生或抑制1,25(OH)2维生素D介导的肠道钙吸收。建议为预防结石复发，EHDP在临床上不仅可应用于磷酸钙结石，还可应用于草酸钙结石以及由活性形式的维生素D介导的高钙尿症。
