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BioMed Research International 2017The high prevalence of arterial calcification in end-stage renal disease (ESRD) is far beyond the explanation by common cardiovascular risk factors such as aging,... (Review)
Review
The high prevalence of arterial calcification in end-stage renal disease (ESRD) is far beyond the explanation by common cardiovascular risk factors such as aging, diabetes, hypertension, and dyslipidemia. The finding relies on the fact that vascular and valvular calcifications are predictors of cardiovascular diseases and mortality in persons with chronic renal failure. In addition to traditional cardiovascular risk factors such as diabetes mellitus and blood pressure control, other ESRD-related risks such as phosphate retention, excess calcium, and prolonged dialysis time also contribute to the development of vascular calcification. The strategies are to reverse "calcium paradox" and lower vascular calcification by decreasing procalcific factors including minimization of inflammation (through adequate dialysis and by avoiding malnutrition, intravenous labile iron, and positive calcium and phosphate balance), correction of high and low bone turnover, and restoration of anticalcification factor balance such as correction of vitamin D and K deficiency; parathyroid intervention is reserved for severe hyperparathyroidism. The role of bone antiresorption therapy such as bisphosphonates and denosumab in vascular calcification in high-bone-turnover disease remains unclear. The limited data on sodium thiosulfate are promising. However, if calcification is to be targeted, ensure that bone health is not compromised by the treatments.
Topics: Humans; Kidney Failure, Chronic; Phosphates; Renal Dialysis; Risk Factors; Vascular Calcification; Vitamin D Deficiency; Vitamin K Deficiency
PubMed: 28286773
DOI: 10.1155/2017/9035193 -
PloS One 2019The purpose of this study was to evaluate the impact of hemodialysis on the concentrations of sodium and potassium in the blood when a 25 g dose of sodium thiosulfate...
INTRODUCTION
The purpose of this study was to evaluate the impact of hemodialysis on the concentrations of sodium and potassium in the blood when a 25 g dose of sodium thiosulfate injection is infused over 60 minutes in combination with hemodialysis.
METHODS
Sodium thiosulfate (25 g) was prepared by diluting 100 mL of 250 mg/mL Sodium Thiosulfate Injection with 800 mL of 5% dextrose. This was added to the circulating blood surrogate solution at a rate of 15 mL/minute using an infusion pump of an in vitro model of dialysis machine. Serial samples were collected before the administration of the sodium thiosulfate solution, after 15 minutes, 30 minutes, and 60 minutes of infusion from pre-and post-dialyzer ports in both the dialysate circuit and the extracorporeal circuit.
FINDINGS
The concentration of sodium thiosulfate in pre-dialyzer and post-dialyzer samples of the circulating blood surrogate solution peaked at 30 minutes and 15 minutes, respectively and then remained relatively unchanged during the remainder of the infusion. Mean sodium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 103.2 ± 12.2, 114.2 ± 18.8, 117.2 ± 7.5, 93.5 ± 5.9 at 0, 15, 30, and 60 minutes, respectively (p = 0.248). Mean potassium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 1.4 ± 0.3, 1.6 ± 0.3, 1.5 ± 0.1, 1.2 ± 0.1 at 0, 15, 30, and 60 minutes, respectively (p = 0.365). Sodium and potassium concentrations in dialysate increased marginally after exposure to the dialyzer.
DISCUSSION
Our study demonstrates that neither potassium nor sodium accumulated in circulating blood surrogate solution when a dose of sodium thiosulfate was infused in conjunction with hemodialysis.
Topics: Blood Substitutes; Dialysis Solutions; In Vitro Techniques; Potassium; Renal Dialysis; Sodium; Thiosulfates
PubMed: 31721800
DOI: 10.1371/journal.pone.0224767 -
Colombia Medica (Cali, Colombia) Dec 2018Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal...
INTRODUCTION
Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required.
CLINICAL CASE
A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis.
TREATMENT AND OUTCOME
Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment.
CONCLUSION
The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.
Topics: Administration, Intravenous; Aged; Calciphylaxis; Chelating Agents; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Pamidronate; Renal Dialysis; Thiosulfates; Treatment Outcome
PubMed: 30700922
DOI: 10.25100/cm.v49i3.4134 -
PloS One 2015Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS,...
BACKGROUND
Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS, Na2S2O3) is an anti-oxidant, which has been used in human medicine for decades. The effect of STS on hyperoxaluria-induced renal damage is not known.
METHODS
Hyperoxaluria and renal injury were induced in healthy male Wistar rats by chronic exposure to ethylene glycol (EG, 0.75%) in the drinking water for 4 weeks. The treatment effects of STS, NaCl or Na2SO4 were compared. Furthermore, the effects of STS on oxalate-induced oxidative stress were investigated in vitro in renal LLC-PK1 cells.
RESULTS
Chronic EG exposure led to hyperoxaluria, oxidative stress, calcium oxalate crystalluria and crystal deposition in the kidneys. Whereas all tested compounds significantly reduced crystal load, only STS-treatment maintained tissue superoxide dismutase activity and urine 8-isoprostaglandin levels in vivo and preserved renal function. In in vitro studies, STS showed the ability to scavenge oxalate-induced ROS accumulation dose dependently, reduced cell-released hydrogen peroxide and preserved superoxide dismutase activity. As a mechanism explaining this finding, STS was able to directly inactivate hydrogen peroxide in cell-free experiments.
CONCLUSIONS
STS is an antioxidant, which preserves renal function in a chronic EG rat model. Its therapeutic use in oxidative-stress induced renal-failure should be considered.
Topics: Animals; Antioxidants; Disease Models, Animal; Hyperoxaluria; Kidney; Kidney Function Tests; Male; Oxidation-Reduction; Oxidative Stress; Rats; Reactive Oxygen Species; Thiosulfates
PubMed: 25928142
DOI: 10.1371/journal.pone.0124881 -
Journal of Interventional Cardiology 2020In animal studies, hydrogen sulfide (HS) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the HS...
Safety and Tolerability of Sodium Thiosulfate in Patients with an Acute Coronary Syndrome Undergoing Coronary Angiography: A Dose-Escalation Safety Pilot Study (SAFE-ACS).
BACKGROUND
In animal studies, hydrogen sulfide (HS) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the HS donor sodium thiosulfate (STS) in patients with acute coronary syndrome (ACS).
METHODS
Eighteen patients, undergoing coronary angiography for ACS, received STS intravenously immediately after arrival at the catheterization laboratory according to a "3 + 3 dose-escalation design" with fixed dosing endpoint (0, 2.5, 5, 10, 12.5, and 15 grams). This first dose STS was combined with verapamil and nitroglycerin required for transradial procedures. A second dose STS was administered 6 hours later. Primary endpoint was dose-limiting toxicity, defined as significant hemodynamic instability or death up to 24 hours or before discharge from the coronary care unit. Secondary outcomes included the occurrence of anaphylaxis, nausea, vomiting, and systolic blood pressure (SBP) course.
RESULTS
Sixteen patients received two dosages of STS and two patients one dosage. None of the patients reached the primary endpoint, nor experienced a serious adverse event. We observed a clinically well-tolerated decline in SBP 1 hour after administration of the first STS dose and concomitant verapamil/nitroglycerin. SBP for all patients together reduced 16.8 (8.1-25.5) mmHg ( = 0.0008). No significant decline in SBP occurred after the second dose. Mild nausea was observed in one patient.
CONCLUSION
This is the first report on sodium thiosulfate administration in patients with acute coronary syndromes. Our data suggest that sodium thiosulfate was well tolerated in this setting. The potential benefit of this intervention has to be examined in larger studies.
Topics: Acute Coronary Syndrome; Adult; Coronary Angiography; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Myocardial Reperfusion Injury; Pilot Projects; Protective Agents; Thiosulfates
PubMed: 33041696
DOI: 10.1155/2020/6014915 -
Cardiovascular Diabetology Mar 2005Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the... (Review)
Review
Vascular ossification-calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis-calcific uremic arteriolopathy: the emerging role of sodium thiosulfate.
BACKGROUND
Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling). The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall.
RESULTS
The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician-researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare) is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisoning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication.
CONCLUSION
A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications.
Topics: Animals; Antioxidants; Arteries; Atherosclerosis; Calcinosis; Calciphylaxis; Chelating Agents; Chronic Disease; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Kidney Diseases; Metabolic Syndrome; Oxidation-Reduction; Pericytes; Reactive Oxygen Species; Thiosulfates; Vasa Vasorum; Vascular Diseases
PubMed: 15777477
DOI: 10.1186/1475-2840-4-4 -
The Journal of Clinical and Aesthetic... Oct 2021The use of sodium thiosulfate has emerged as a promising treatment for calciphylaxis, albeit inconclusively in terms of efficacy and variable outcomes. Research in this...
The use of sodium thiosulfate has emerged as a promising treatment for calciphylaxis, albeit inconclusively in terms of efficacy and variable outcomes. Research in this field has been limited by a paucity of samples due to the rarity of the disease. We herein discuss eight calciphylaxis patients' responses to STS, the potential predictive factors affecting outcomes and compare our results with previously published literature. We are able to show that lesion severity, concomitant drugs, and dialysis duration may be predictive factors of outcomes. Further, improvement of the wound site may be a clinically relevant prognostic determinant.
PubMed: 34976291
DOI: No ID Found -
Biomolecules Apr 2022Ever since the discovery of endogenous HS and the identification of its cytoprotective properties, efforts have been made to develop strategies to use HS as a... (Review)
Review
Ever since the discovery of endogenous HS and the identification of its cytoprotective properties, efforts have been made to develop strategies to use HS as a therapeutic agent. The ability of HS to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous HS, nor the administration of inorganic HS-releasing salts or slow-releasing HS-donors are feasible for clinical use. NaSO is a clinically approved compound with a good safety profile and is able to release HS, in particular under hypoxic conditions. Pre-clinical studies show promise for NaSO in the acute management of critical illness. A current clinical trial is investigating the therapeutic potential for NaSO in myocardial infarct. Pre-eclampsia and COVID-19 pneumonia might be relevant targets for future clinical trials.
Topics: Critical Illness; Humans; Hydrogen Sulfide; Thiosulfates; COVID-19 Drug Treatment
PubMed: 35454132
DOI: 10.3390/biom12040543 -
JCI Insight Dec 2023The widely used chemotherapy cisplatin causes permanent hearing loss in 40%-60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in...
The widely used chemotherapy cisplatin causes permanent hearing loss in 40%-60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in pediatric patients with localized solid tumors for preventing cisplatin-induced hearing loss, but more drugs are desperately needed. Here, we tested dabrafenib, an FDA-approved BRAF kinase inhibitor and anticancer drug, in a clinically relevant multidose cisplatin mouse model. The protective effects of dabrafenib, given orally twice daily with cisplatin, were determined by functional hearing tests and cochlear outer hair cell counts. Toxicity of the drug cotreatment was evaluated, and levels of phosphorylated ERK were measured. A dabrafenib dose of 3 mg/kg BW, twice daily, in mice, was determined to be the minimum effective dose, and it is equivalent to one-tenth of the daily FDA-approved dose for human cancer treatment. The levels of hearing protection acquired, 20-25 dB at the 3 frequencies tested, in both female and male mice, persisted for 4 months after completion of treatments. Moreover, dabrafenib exhibited a good in vivo therapeutic index (> 25), protected hearing in 2 mouse strains, and diminished cisplatin-induced weight loss. This study demonstrates that dabrafenib is a promising candidate drug for protection from cisplatin-induced hearing loss.
Topics: Humans; Male; Female; Child; Mice; Animals; Cisplatin; Hearing Loss; Antineoplastic Agents; Imidazoles; Neoplasms; Deafness
PubMed: 37934596
DOI: 10.1172/jci.insight.171140 -
Japanese Journal of Pharmacology Dec 1981The protective effect of sodium thiosulfate and thiourea on the lethal toxicity of the antitumor drug, cis-diamminedichloroplatinum (II) (cis-DDP), was investigated in...
The protective effect of sodium thiosulfate and thiourea on the lethal toxicity of the antitumor drug, cis-diamminedichloroplatinum (II) (cis-DDP), was investigated in bacteria and mice. Initially, the agents capable of antagonizing bactericidal activity of cis-DDP were screened using WP2 uvra, a strain of E. coli sensitive to this drug. Of the ten sulfur-containing compounds tested, thiourea and sodium thiosulfate exhibited potent protecting effects against cis-DDP cytotoxicity in bacteria. Propylthiouracil and methimazole showed intermediate levels of such protection, but the other 6 compounds had little or no protective effects. Thiourea and sodium thiosulfate were then subjected to the acute lethal toxicity test in mice to assess their protective activity in vivo. We found that cis-DDP i.v. lethality against mice can be blocked almost completely by excess amounts of thiourea or sodium thiosulfate. Thiourea protected against cis-DDP toxicity with a narrow range among the effective doses, while sodium thiosulfate was protective with a remarkably wide range of effective doses. The effectiveness of sodium thiosulfate was also indicated in experiments in which the LD50 dose of cis-DDP (16 mg/kg) i.p. increased over the level of greater than 200 mg/kg with concomitant administration of sodium thiosulfate i.p.
Topics: Animals; Bacteria; Cisplatin; Escherichia coli; Female; Lethal Dose 50; Mice; Mice, Inbred Strains; Thiosulfates; Thiourea
PubMed: 6801366
DOI: 10.1254/jjp.31.883