Thiosulfate Reduces Calcium Phosphate Nephrolithiasis

Asplin, John R.; Donahue, S.; Lindeman, Christina; Michalenka, Anne; Strutz, Kelly Laplante; Bushinsky, David A.

doi:10.1681/asn.2008070754

Cited by 53 publications

(66 citation statements)

References 36 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alternatively, the low and variable bioavailability may be due to STS degradation by intestinal bacteria (26) and/or different expression levels of a putative TS transporter in the gut mucosa, which might exist in analogy to a sulfate-inhibitable TS transporter in the dog renal tubule (27). Interestingly, despite the very low oral bioavailability of STS, the successful prevention of renal stones in humans (28), and rats (29), and of the progression of calciphylaxis (30) and nephrocalcinosis (31) has been reported by comparable oral STS doses as those used in our investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we showed for the first time that the nonrenal clearance of TS is similar in hemodialysis patients and in HV ( Table 4). The vast proportion of TS cleared by nonrenal mechanisms appears to be metabolized to sulfate (4,29,38) possibly predominantly in the liver but also in other tissues (39). TS is considered to be the principal, rapidly disappearing precursor of sulfate in mammalians (40).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Farese¹,

Stauffer²,

Kalicki³

et al. 2011

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground and objectives Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.Design, setting, participants, & measurements STS was given intravenously to 10 hemodialysis patients onand off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. ResultsIn volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 Ϯ 1.82 versus 7.1 Ϯ 2.7 mol/L. Renal clearance was high in volunteers (1.86 Ϯ 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 Ϯ 0.32 ml/min per kg) than in anuric patients (2.04 Ϯ 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 Ϯ 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). ConclusionsGiven the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Farese¹,

Stauffer²,

Kalicki³

et al. 2011

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…The drug, approved only for treatment of cyanide poisoning and calcific uremic arteriolopathy, causes metabolic acidosis and reduces urine pH. It was effective in preventing calcium phosphate stones in the genetic hypercalciuric stone-forming rat (30). It has similar effects on urine chemistry in healthy controls and people with hypercalciuria in our own recent study (ClinicalTrials.…”

Section: Therapeutic Optionsmentioning

confidence: 97%

A Woman with Recurrent Calcium Phosphate Kidney Stones

Goldfarb

2012

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryKidney stones composed predominantly (50% or more) of calcium phosphate constitute up to 10% of all stones and 15%-20% of calcium stones, 80% of which are composed of calcium oxalate. Calcium phosphate is a minor component of up to 30% of calcium oxalate stones as well. The cause of calcium phosphate stones is often obscure but most often related to a high urine pH. Some patients with calcium phosphate stones may have incomplete renal tubular acidosis. Others have distal renal tubular acidosis characterized by hyperchloremic acidosis, hypocitraturia, and high urine pH. The use of carbonic anhydrase inhibitors such as acetazolamide, topiramate, and zonisamide leads to a similar picture. Treatment options to specifically prevent calcium phosphate stone recurrence have not been tested in clinical trials. Increases in urine volume and restriction of sodium intake to limit calcium excretion are important. Citrate supplementation is probably effective, although the concomitant increase in urine pH may increase calcium phosphate supersaturation and partially offset the inhibition of crystallization resulting from the increased urine citrate excretion and the alkali-associated reduction in urine calcium excretion. Thiazides lower urine calcium excretion and may help ensure the safety of citrate supplementation.

show abstract

“…The upper limit of metastability (ULM) of CaOx and calcium phosphate (CaP) in human urine was measured using a modification of the method of Asplin and colleagues (10). Sequential aliquots of calcium chloride (CaP ULM) or 5 ml oxalic acid solution (CaOx ULM) were added to urine in a temperature-controlled cuvette under constant stirring, and the point of precipitation was assessed at a wavelength of 620 nm using a Cary Bio 50 UV-Visible spectrophotometer (Agilent Technologies, Inc., Santa Clara, CA).…”

Section: Crystal Growth Inhibition Assaymentioning

confidence: 99%

Heritability of Urinary Traits That Contribute to Nephrolithiasis

Lieske

Turner

Edeh

et al. 2014

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives Kidney stones and their risk factors aggregate in families, yet few studies have systematically estimated heritabilities and genetic correlations of the numerous urinary traits associated with risk of kidney stones.Design, setting, participants, & measurements Twenty-four-hour urine samples were collected from the Genetic Epidemiology Network of Arteriopathy cohort of families in Rochester, Minnesota, to measure urinary determinants of supersaturation. Diet was assessed using the Viocare food frequency questionnaire. Heritabilities and genetic correlations among the urinary traits were estimated using variance components methods.Results Samples were available from 811 individuals (344 men, 467 women; mean age 6669 years). Age, sex, and weight were significantly correlated with the majority of urinary traits. Many urine excretions (calcium, magnesium, citrate excretion) had strong evidence for heritability (P,0.01) both before and after adjusting for the identified covariates. Among significantly heritable urinary traits, genetic factors explained 20%-36% of interindividual variation after adjustment for covariates. Urinary calcium excretion was significantly genetically correlated with urinary magnesium and with urinary citrate excretion (P,0.05). Although eGFR influenced many urinary traits, controlling for eGFR did not greatly affect estimated heritabilities.Conclusions Evidence from this cohort suggests a strong heritable component to many urinary nephrolithiasis risk factors. Further study of genetic influences on urinary traits relevant for kidney stone pathogenesis is warranted.Clin J Am Soc Nephrol 9: 943-950, 2014.

show abstract

Thiosulfate Reduces Calcium Phosphate Nephrolithiasis

Cited by 53 publications

References 36 publications

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

A Woman with Recurrent Calcium Phosphate Kidney Stones

Heritability of Urinary Traits That Contribute to Nephrolithiasis

Contact Info

Product

Resources

About