Department of Medicine, New York Harbor VA Healthcare System and NYU School of Medicine, New York, New York, United States of America.
PLoS One. 2013 Apr 8;8(4):e60380. doi: 10.1371/journal.pone.0060380. Print 2013.
Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. DESIGN SETTING PARTICIPANTS MEASUREMENTS: STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry.
STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate.
The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO3 did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.
硫代硫酸钠(STS)可减少人和遗传性高钙尿结石形成(GHS)大鼠的钙结石形成。我们试图测量 STS 给药后尿液化学变化。
设计、设定、参与者、测量:STS 给予健康和高钙尿结石形成的成年人。5 名正常非结石形成的成年人(平均年龄 33 岁)和 5 名特发性高钙尿和钙肾结石患者(平均年龄 66 岁)参与了研究。在 3 天的自我选择饮食中,第 2 天和第 3 天进行了 2 次基线 24 小时尿液收集。然后,受试者每天两次饮用 STS 10mmol,共 7 天,并在重复自我选择饮食时进行尿液收集。结果通过非参数 Wilcoxon 符号秩检验进行比较。主要结果是尿液化学的变化。
STS 给药在两组中均未导致尿钙排泄的显著变化。在两组中,24 小时尿铵(P=0.005)和硫酸盐排泄(P=0.007)增加,尿 pH 值下降(P=0.005);在高钙尿患者中,柠檬酸排泄减少(P<0.05),而非结石形成者则没有。在高钙尿结石形成者中,有 3 名患者在 STS 期间测量了血清 HCO3 浓度:它没有改变。总的结果是尿酸过饱和度增加,而草酸钙和磷酸钙过饱和度没有变化。
STS 预防大鼠和人类结石的研究依据并未反映在此处报告的尿液化学变化。尽管血清 HCO3 没有改变,但尿液测试提示非结石形成者和高钙尿结石形成者均存在酸负荷。在 STS 可用于人类长期预防结石复发之前,需要确定其长期安全性。