Pasch Andreas, Schaffner Thomas, Huynh-Do Uyen, Frey Brigitte M, Frey Felix J, Farese Stefan
Department of Nephrology and Hypertension, Inselspital, University of Bern, Bern, Switzerland.
Kidney Int. 2008 Dec;74(11):1444-53. doi: 10.1038/ki.2008.455. Epub 2008 Sep 24.
Accelerated vascular calcification is a severe complication of chronic kidney disease contributing to high morbidity and mortality in patients undergoing renal replacement therapy. Sodium thiosulfate is increasingly used for the treatment of soft tissue calcifications in calciphylaxis. Therefore, we determined whether it also prevents development of vascular calcifications in chronic kidney disease. We found that uremic rats treated by thiosulfate had no histological evidence of calcification in the aortic wall whereas almost three-fourths of untreated uremic rats showed aortic calcification. Urinary calcium excretion was elevated and the calcium content of aortic, heart, and renal tissue was significantly reduced in the thiosulfate-treated compared to non-treated animals. Sodium thiosulfate treatment transiently lowered plasma ionized calcium and induced metabolic acidosis. It also lowered bone strength in the treated animals compared to their normal controls. Hence, sodium thiosulfate prevented vascular calcifications in uremic rats, likely by enhancing acid- and/or chelation-induced urinary calcium loss. The negative impact on rat bone integrity necessitates a careful risk-benefit analysis before sodium thiosulfate can be used in individual human patients.
血管钙化加速是慢性肾脏病的一种严重并发症,会导致接受肾脏替代治疗的患者出现高发病率和高死亡率。硫代硫酸钠越来越多地用于治疗钙化防御中的软组织钙化。因此,我们确定它是否也能预防慢性肾脏病中的血管钙化发展。我们发现,用硫代硫酸钠治疗的尿毒症大鼠主动脉壁没有钙化的组织学证据,而几乎四分之三未经治疗的尿毒症大鼠出现主动脉钙化。与未治疗的动物相比,硫代硫酸钠治疗的大鼠尿钙排泄增加,主动脉、心脏和肾脏组织的钙含量显著降低。硫代硫酸钠治疗可使血浆离子钙暂时降低并诱发代谢性酸中毒。与正常对照组相比,它还降低了治疗动物的骨强度。因此,硫代硫酸钠可能通过增强酸诱导和/或螯合诱导的尿钙流失来预防尿毒症大鼠的血管钙化。在将硫代硫酸钠用于个体人类患者之前,其对大鼠骨骼完整性的负面影响需要进行仔细的风险效益分析。