A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone Formers and Stone Formers with Hypercalciuria

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...

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Published inPloS one Vol. 8; no. 4; p. e60380
Main Authors Okonkwo, Onyeka W., Batwara, Ruchika, Granja, Ignacio, Asplin, John R., Goldfarb, David S.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 08.04.2013
Public Library of Science (PLoS)
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Summary: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.
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Conceived and designed the experiments: OO RB JA DG. Performed the experiments: OO RB IG JA DG. Analyzed the data: JA RB DG. Contributed reagents/materials/analysis tools: JA IG. Wrote the paper: OO DG RB JA.
Competing Interests: Ignacio Granja and John R. Asplin are employed by Litholink. John R. Asplin is a consultant to Oxthera Corp. David S. Goldfarb is a consultant for Takeda and Keryx and a speaker for CME Quintiles, Mission and owner, Ravine Group. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060380