Sodium thiosulfate delays the progression of coronary artery calcification in haemodialysis patients

Adirekkiat, Surawat; Sumethkul, V.; Ingsathit, Atiporn; Domrongkitchaiporn, Somnuek; Phakdeekitcharoen, Bunyong; Kantachuvesiri, Surasak; Kitiyakara, Chagriya; Klyprayong, Pinkaew; Disthabanchong, Sinee

doi:10.1093/ndt/gfp755

Cited by 68 publications

(64 citation statements)

References 35 publications

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“…Although no large, prospective, randomized trials examining the role of STS in reducing vascular calcification have been published, one small nonrandomized study has studied this in HD patients [15]. In this study, 49 patients with a CAC Agatston score ≥300 were enrolled; of these, 16 were selected to receive STS and another 15 comprised a concurrent nonrandomized control group.…”

Section: Discussionmentioning

confidence: 99%

Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy

et al. 2011

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Background and Objectives: Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients. Methods: Chronic hemodialysis patients underwent a battery of cardiovascular tests. Those with coronary artery calcium (Agatston scores >50) received intravenous STS after each dialysis for 5 months (n = 22) and the tests were repeated. Changes in MDCT-determined calcification were assessed as the mean annualized rate of change in 3 vascular beds (coronary, thoracic and carotid arteries) and in L1-L2 vertebral bone density. Results: Although individual analyses showed coronary artery calcification progression in 14/22 subjects, there was no progression in the mean annualized rate of change of vascular calcification in the entire group. The L1-L2 vertebral bone density showed no changes. There were no correlations between rates of progression of vascular calcification and phosphorus, fetuin or C-reactive protein levels. Changes in coronary artery calcification scores correlated with those of the thoracic aorta. Conclusion: STS treatment is feasible, appears safe and may decrease the rate of progression of vascular calcification in hemodialysis patients. A large, randomized, controlled trial is warranted.

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Section: Discussionmentioning

confidence: 99%

Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy

et al. 2011

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“…Intravenous infusion of 25% STS solution immediately after hemodialysis for 60 times during 5 months was well tolerated in most patients [126], and calcific uremic arteriolopathy improved in a large observational study [127]. In one study which evaluated the effect of STS on CAC, twice weekly STS infusion post-hemodialysis for 4 months delayed the progression of CAC compared with non-treated control (p = 0.03) [130]. CACS was unchanged in the STS-treated group but increased significantly in the non-treated control group.…”

Section: Sodium Thiosulfatementioning

confidence: 99%

Impact of vascular calcification on cardiovascular mortality in hemodialysis patients: clinical significance, mechanisms and possible strategies for treatment

Ohtake

Kobayashi

2017

Ren Replace Ther

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Vascular calcification has now been recognized as a major problem in dialysis patients because of its strong influence on the prognosis. Along with the regulatory failure of calcification-inhibitory system, active phenotypic change of vascular smooth muscle cells (VSMCs) to osteoblast-like cells is also involved in the progression of vascular calcification. Delaying or improving the vascular calcification is thought to be very important to improve the cardiovascular mortality in dialysis patients. Several interventional trials against vascular calcification using non-calcium-containing phosphate binders, low-dose active vitamin D plus cinacalcet, modification of dialysate calcium concentration, and sodium thiosulfate have been done, and some trials including non-calcium-containing phosphate binders showed beneficial effect on delaying vascular calcification in dialysis patients. However, delaying or improving vascular calcification has not been clearly proved to result in improved cardiovascular event and/or mortality rate by prospective interventional randomized controlled trials in dialysis patients. Whether the improvement of vascular calcification could directly lead to the improvement of survival is an urgent issue of clinical trials in dialysis patients.

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“…Recently, STS has been prescribed for the treatment of soft-tissue calcifications in patients with calciphylaxis (7)(8)(9)(10)(11)(12). Furthermore, systematic studies in rats (13) and humans (14) have investigated the effect of STS on aortic and coronary artery calcifications. These studies support the notion of vascular calcification, slowing or even preventing properties of STS.…”

Section: Introductionmentioning

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

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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.

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Sodium thiosulfate delays the progression of coronary artery calcification in haemodialysis patients

Abstract: The effect of sodium thiosulfate in delaying the progression of CAC is encouraging and will require a larger study. Determination of the safe therapeutic window is necessary in order to avoid bone demineralization.

Cited by 68 publications

References 35 publications

Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy

Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy

Impact of vascular calcification on cardiovascular mortality in hemodialysis patients: clinical significance, mechanisms and possible strategies for treatment

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

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