Influence of sodium thiosulfate on coronary artery calcification of patients on dialysis: a meta-analysis.

Coronary artery calcification (CAC) is common in dialysis patients and is associated with a higher risk of future cardiovascular events. Sodium thiosulfate (STS) is effective for calciphylaxis in dialysis patients; however, the influence of STS on CAC in dialysis patients remains unclear. This systematic review and meta-analysis were conducted to evaluate the effects of STS on CAC in patients undergoing dialysis. PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched from inception to 22 March 2023 for controlled studies comparing the influence of STS versus usual care without STS on CAC scores in dialysis patients. A random effects model incorporating the potential influence of heterogeneity was used to pool the results. Nine studies, including two non-randomized studies and seven randomized controlled trials, were included in the meta-analysis. Among these, 365 patients on dialysis were included in the study. Compared with usual care without STS, intravenous STS for 3-6 months was associated with significantly reduced CAC scores (mean difference [MD] = -180.17, 95% confidence interval [CI]: -276.64 to -83.70, p < 0.001, I2 = 0%). Sensitivity analysis limited to studies of patients on hemodialysis showed similar results (MD: -167.33, 95% CI: -266.57 to -68.09, p = 0.001; I2 = 0%). Subgroup analyses according to study design, sample size, mean age, sex, dialysis vintage of the patients, and treatment duration of STS also showed consistent results (p for subgroup differences all > 0.05). In conclusion, intravenous STS may be effective in attenuating CAC in dialysis patients.

Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial.

BACKGROUND: Ischemia and subsequent reperfusion cause myocardial injury in patients presenting with ST-segment elevation myocardial infarction (STEMI). Hydrogen sulfide (H2S) reduces "ischemia-reperfusion injury" in various experimental animal models, but has not been evaluated in humans. This trial will examine the efficacy and safety of the H2S-donor sodium thiosulfate (STS) in patients presenting with a STEMI. STUDY DESIGN: The Groningen Intervention study for the Preservation of cardiac function with STS after STEMI (GIPS-IV) trial (NCT02899364) is a double-blind, randomized, placebo-controlled, multicenter trial, which will enroll 380 patients with a first STEMI. Patients receive STS 12.5 grams intravenously or matching placebo in addition to standard care immediately at arrival at the catheterization laboratory after providing consent. A second dose is administered 6 hours later at the coronary care unit. The primary endpoint is myocardial infarct size as quantified by cardiac magnetic resonance imaging 4 months after randomization. Secondary endpoints include the effect of STS on peak CK-MB during admission and left ventricular ejection fraction and NT-proBNP levels at 4 months follow-up. Patients will be followed-up for 2 years to assess clinical endpoints. CONCLUSIONS: The GIPS-IV trial is the first study to determine the effect of a H2S-donor on myocardial infarct size in patients presenting with STEMI.

Improved microvascular reactivity after aged garlic extract intake is not mediated by hydrogen sulfide in older adults at risk for cardiovascular disease: a randomized clinical trial.

PURPOSE: This study aimed to investigate the effects of AGE on microvascular reactivity, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in older individuals at high risk for cardiovascular disease (CVD). Urinary thiosulfate was also investigated as an indirect marker of endogenous hydrogen sulfide (H2S) synthesis. The study was conducted in a randomized, double-blind, crossover, and placebo-controlled way. METHODS: Twenty-eight participants (14 male), 67 ± 6 years old with CVD risk factors, ingested 2.4 g of AGE or placebo (PLA). Near-infrared spectroscopy evaluated tissue oxygen saturation (StO2) during a vascular occlusion test (30 s baseline, 5 min occlusion, and 2 min reperfusion). The upslope of StO2 signal after cuff release was calculated to measure microvascular reactivity. Urinary thiosulfate levels were measured using a high-performance liquid chromatography system. RESULTS: The upslope of StO2 was significantly faster after AGE (1.01 ± 0.37% s-1) intake compared to PLA (0.83 ± 0.35% s-1; P < 0.001; d = 0.50). Relative changes in Δ% SBP from pre- to post-AGE intake (- 5.17 ± 5.77%) was significantly different compared to Δ% PLA (0.32 ± 5.99%; P = 0.001; d = 0.93). No significant changes in urinary thiosulfate concentrations were observed between interventions. Moreover, no significant gender effect in any parameter assessed was found. CONCLUSION: This study demonstrated that a single dose of AGE improved microvascular reactivity in older adults at risk of CVD despite such an effect was not linked with urinary thiosulfate levels. This trial was registered at clinicaltrials.gov as NCT04008693 (May 19, 2020).

Success of small-dose fractionated sodium thiosulfate in the treatment of calciphylaxis in a peritoneal dialysis patient.

BACKGROUND: Calciphylaxis, or calcific uremic arteriolopathy (CUA), is a rare, fatal disorder of microvascular calcification and thrombosis that typically affects patients with end-stage renal disease (ESRD) receiving long-term dialysis. Fewer reports describe calciphylaxis in peritoneal dialysis patients than hemodialysis patients as per a literature review. To date, there are no clear guidelines for CUA diagnosis and treatment. While sodium thiosulfate (STS) has been increasingly used for treatment in recent years, there have also been reports of severe side effects. There is no uniform standard for its usage and dosage, especially for peritoneal dialysis patients. CASE PRESENTATION: We present a case of a 40-year-old Chinese male patient with ESRD on peritoneal dialysis who developed calciphylaxis with severe painful cutaneous ulcers on the fingers and toes that were managed successfully for 6 months with comprehensive treatment composed mainly of small-dose fractionated sodium thiosulfate. CONCLUSIONS: Our experience suggests that the treatment of calciphylaxis requires timely and multi-angle intervention. Treatment with small-dose fractionated sodium thiosulfate has proven effective and tolerated in this patient.

Lack of response to intravenous sodium thiosulfate in three cases of extensive connective tissue disease-associated calcinosis cutis.

Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD-associated dystrophic calcinosis cutis. We report three patients with long-standing and extensive CTD-associated calcinosis cutis treated with IV STS after having failed multiple prior therapies. All three patients experienced fatigue and nausea with STS infusions, and none of the patients had notable clinical or symptomatic improvement of calcinosis. It remains to be seen whether the administration of IV STS earlier in the onset of calcinosis might be of benefit given that these patients all had long-standing and refractory CTD-associated calcinosis. Given the small number of patients in this series, further investigation into the use of IV STS in calcinosis cutis is warranted.

Systematic review of sodium thiosulfate in treating calciphylaxis in chronic kidney disease patients.

AIM: Calciphylaxis is a severe complication of advanced chronic kidney disease (CKD). Sodium thiosulphate (STS), an antioxidant and calcium chelating agent, has been used for the treatment of calciphylaxis. However, its efficacy and safety have not been systematically analysed and evaluated. METHODS: MEDLINE, EMBASE, and the Cochrane Library database were systematically searched for case report or cases series on use of STS for calciphylaxis published between July 1974 and October 2016. We extracted data on clinical characteristics, laboratory tests result and medication use. The effective treatment was defined as improvement in skin lesion cicatrisation or pain relief without death. Non-responding effects were defined as stable skin lesions without remission or exacerbation of the disease in patients who remained alive. All-cause mortality after STS treatment was defined as death due to exacerbations of calciphylaxis or other complications of advanced CKD. We compared the baseline parameters of the patients as well as the efficacy and mortality of the STS therapy between case report and multi-case reports. Statistical analyses were performed using SPSS 19. RESULTS: A total of 83 papers were screened, 45 of them (n = 358) met the inclusion criteria, including 36 case reports (n = 64) and nine multi-case reports (n = 294). The mean age of the patients with calciphylaxis was 58 ± 14 years (range 26-91 years). They were female predominant, accounting for 74.1%. Among the patients with calciphylaxis, 96.1% patients were on dialysis with median dialysis vintage of 44.5 months (range 24-84 months). STS was effective in 70.1% of patients, 37.6% patients died. The proportion of patients with sepsis was higher among those who received intravenous STS. There was no significant difference in efficacy between the different STS administration methods (P = 0.19). CONCLUSION: Although the study was unable to assess the efficacy of sodium thiosulphate alone in the treatment of calciphylaxis, it still reveals a promising role of STS as an effective therapy for calciphylaxis. Further prospective studies to define the optimal therapy for calciphylaxis are needed.

Treatment of Calciphylaxis: A Case for Oral Sodium Thiosulfate.

Calciphylaxis is a major cause of morbidity and mortality in end-stage renal disease (ESRD). Intravenous sodium thiosulfate (STS) is the mainstay of therapy for calciphylaxis. In peritoneal dialysis (PD) patients with calciphylaxis, intravenous STS poses logistic and financial challenges. Even though pharmacokinetic studies show poor bioavailability of oral STS, we report successful use of oral STS in 2 PD patients with calciphylaxis.A 55-year-old Latina American woman with diabetes was initiated on PD after access failure and chronic hypotension. She developed painful ischemic lesions in the left middle finger and left big toe 4 months later. The ischemia in the left hand progressed, requiring amputation of two fingers. She later developed extensive painful calcific areas in the abdominal wall. She was initially started on oral STS 1500 mg twice daily that was subsequently increased to 3750 mg daily, which resulted in substantial pain relief and a decrease in the size of the calcific plaques.Another diabetic patient with ESRD who was on PD presented with a painful ischemic finger for 2 years. He was treated with oral STS 1500 mg twice daily, resulting in prompt pain relief.Oral STS can be an effective treatment for calciphylaxis.

Sodium thiosulfate for the treatment of calcinosis secondary to juvenile dermatomyositis.

We report the successful use of sodium thiosulfate in a patient with juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This therapy may have a role in improving calcinosis, even if more studies are necessary to determine the safety and efficacy of this treatment in juvenile dermatomyositis-related calcinosis.

Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature.

PURPOSE: Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN: A comprehensive narrative review is presented. RESULTS: Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION: Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.

Multi-modal treatment of calciphylaxis with sodium-thiosulfate, cinacalcet and sevelamer including long-term data.

BACKGROUND: Calciphylaxis is a rare, yet life-threatening disease mainly occurring in dialysis patients. Traditional options of treatment remain unsatisfactory. METHODS: Here we present a novel, combined approach, treating calciphylaxis with IV sodium thiosulfate, cinacalcet and sevelamer. In a case series five hemodialysis patients, have been successfully treated with this regimen. Treatment and survival data were analyzed using descriptive statistics. RESULTS: In all patients, a rapid decrease in pain, improvement of general condition and wound healing within six months occurred. Side effects were low. Drug dosages: IV sodium thiosulfate initial dose 119.4 +/- 84.9 g/m(2)/week, maintenance dose 40.6 +/- 9 g/m(2)/week; cinacalcet: maintenance dose 36 +/- 32.9 mg/d and sevelamer maintenance dose 3320 +/-1671 mg/d. One and two year survivals were 100 % and 80 %, respectively. We also report on long-term application of IV sodium thiosulfate of up to 52 months. Patient survival after diagnosis was 52, 84, 21, 36 and 30 months, respectively. Survival since initiation of hemodialysis was 76, 136, 89, 36 and 35 months, respectively. CONCLUSION: This novel combined approach, a multi-modal treatment of calciphylaxis with persistent hyperparathyroidism, using IV sodium thiosulfate, cinacalcet and sevelamer seems to improve the outcome of this devastating disease.

Calcific uremic arteriolopathy in hemodialyzed patients.

In the present article, we discuss the case of 67-year-old female patient diagnosed with inferior limbs calciphylaxis and hemodialyzed since 2006. The clinical manifestations and pathological lab findings are typical for this rare and extremely severe complication in chronic hemodialyzed individuals. The favorable treatment response to sodium thiosulfate, not often used as elected therapy in international studies, represents the particularity of the case.

Maximal conservative therapy of calcific uremic ateriolopathy.

We present the case of a 61-year- old female patient in long-term hemodialysis who developed calcific uremic arteriolopathy (CUA) upon administration of the oral calcimimetic agent cinacalcet for treatment of secondary hyperparathyroidism. In May 2009, the baseline serum values were parathormone (PTH) 310 pg/ml, calcium 9.1 mg/dl and phosphorous 6.9 mg/dl. Necrotic wounds in the suprapubic fat tissue were successfully treated first, by correcting the calcium phosphorous product; second, through treatment with sodium thiosulfate and third, through intensive wound care with hyperbaric oxygen therapy and vacuum-assisted closure therapy, with no need for parathyroidectomy. Multiple factors have been described to play a role in the development of CUA. Based on the findings of this case, the treatment of CUA should be aimed at correcting different causes simultaneously.

Reactive films for mitigating methyl bromide emissions from fumigated soil.

Emissions of methyl bromide (MeBr) from agricultural fumigation can lead to depletion of the stratospheric ozone layer, and so its use is being phased out. However, as MeBr is still widely used under Critical Use Exemptions, strategies are still required to control such emissions. In this work, novel reactive films (RFs) were designed and their efficacy in limiting loss of MeBr from soil was tested. A reactive layer, containing dry ammonium thiosulfate (ATS), was sandwiched between two layers of plastic film, the lower layer being HDPE (high-density polyethylene film, which is permeable to MeBr) and the upper layer HDPE or VIF (virtually impermeable film). MeBr diffusion through, and transformation by, the RFs were tested in a stainless-steel permeability cell. Although ineffective when dry, the RFs substantially depleted MeBr when activated with water to produce ATS solution. MeBr half-life (t(1/2)) was around 9.0 h at 20 °C in the presence of activated RF, and was sensitive to temperature (t(1/2) 15.7 and 2.9 h at 10 and 40 °C, respectively). When the upper film layer was VIF, less than 0.15% of the added MeBr diffused through the film, with the remainder being transformed within the reactive layer. These findings indicate that such films have good potential to reduce MeBr loss from fumigated soils to the atmosphere.

A novel treatment for ulcerative calcinosis cutis.

BACKGROUND: Calcinosis cutis is a term used to describe a group of disorders which result in calcium deposits in the skin. These disorders can be separated based on etiology. OBJECTIVE AND METHODS: Sodium thiosulfate has been used to systemically treat calciphylaxis with little to no adverse effects. We report two cases of ulcerative calcinosis cutis which were refractory to multiple topical treatments and did not improve with correction of underlying electrolyte abnormalities. RESULTS: Both cases showed an excellent response to topical 25% sodium thiosulfate compounded in zinc oxide. LIMITATIONS: We are limited by a small sample size (n=2) in this case series. CONCLUSIONS: We recommend topical sodium thiosulfate 25% as an alternative treatment for dystrophic calcinosis cutis.