Gupta M, Tuncay O L, Valderrama E, Smith A D
Department of Urology, Long Island Jewish Medical Center, New Hyde Park, NY, USA.
J Endourol. 1997 Feb;11(1):1-4. doi: 10.1089/end.1997.11.1.
Bisphosphonates bind renal calculi and inhibit calcium oxalate crystal growth in vitro. We evaluated their ability to inhibit calcium oxalate urolithiasis in a lithogenic rat model. Male Sprague-Dawley rats (four groups, eight rats each) were fed 1.0% ethylene glycol in their drinking water for 6 weeks. All rats had implantation of a 50- to 60-mg zinc pellet in their urinary bladder at the beginning of the 6-week period. The control group received no treatment. The other three groups received six weekly intraperitoneal injections of one of three bisphosphonates: pamidronate (APD), clodronate (CLO), or methylene diphosphonate (MDP). At the end of 6 weeks, the zinc pellet was retrieved and weighed; the kidneys were sectioned and stained to evaluate inflammation, tubular dilation, and crystal deposition; and blood and urine samples were analyzed for calcium and creatinine. There were no detectable biochemical differences between the control and the treatment groups. Zinc pellets removed from control animals had a significantly greater increase in weight secondary to crystal deposition than those from the treatment groups (mean 28.4% for control v 18.9%, 15.3%, and 18.6%, respectively, for animals given APD, CLO, and MDP). The control animals also had significantly higher scores for inflammation, tubular dilation, and crystal deposition than animals treated with MDP and CLO. Older and newer-generation bisphosphonates have an inhibitory effect on calcium oxalate urolithiasis that is demonstrable at relatively infrequent dosing intervals in vivo. More frequent dosing or higher doses may allow greater inhibition of stone formation.
双膦酸盐可结合肾结石并在体外抑制草酸钙晶体生长。我们在致石性大鼠模型中评估了它们抑制草酸钙尿路结石形成的能力。雄性Sprague-Dawley大鼠（4组，每组8只）饮用含1.0%乙二醇的水6周。在这6周开始时，所有大鼠的膀胱内均植入了一枚50至60毫克的锌丸。对照组未接受任何治疗。其他三组每周接受一次腹腔注射三种双膦酸盐之一：帕米膦酸盐（APD）、氯膦酸盐（CLO）或亚甲基二膦酸盐（MDP），共注射6次。6周结束时，取出锌丸并称重；将肾脏切片并染色以评估炎症、肾小管扩张和晶体沉积；对血液和尿液样本进行钙和肌酐分析。对照组和治疗组之间未检测到生化差异。从对照动物取出的锌丸因晶体沉积导致的重量增加明显大于治疗组（对照组平均增加28.4%，而给予APD、CLO和MDP的动物分别为18.9%、15.3%和18.6%）。对照动物的炎症、肾小管扩张和晶体沉积评分也显著高于接受MDP和CLO治疗的动物。新一代和旧一代双膦酸盐对草酸钙尿路结石形成均有抑制作用，在体内以相对不频繁的给药间隔即可显现。更频繁给药或更高剂量可能会对结石形成产生更大的抑制作用。
