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1.
J Physiol ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264236

ABSTRACT

Sodium thiosulfate (STS) is gaining increasing attention in research for its potential therapeutic applications across a spectrum of disease processes beyond its current uses. However, the precise mechanisms of action remain incompletely understood. We investigated the efficacy of STS in treating hyperglycaemia-induced pronephros damage in zebrafish to gain further insight into the underlying mechanisms. Hyperglycaemia was induced in zebrafish by suppressing the pdx1 transcription factor, which plays a crucial role in maintaining physiological pancreatic function. STS was administered by introducing it into the medium of zebrafish larvae. The pronephros structure was analysed at 48 h post-fertilization. Metabolomic profiling and RNA sequencing were conducted on groups exposed to various experimental conditions. Our findings reveal a downregulation of nitric oxide (NO) signalling in zebrafish with a knocked-down pdx1 gene, both metabolomically and transcriptionally. Notably, treatment with STS led to a compensatory upregulation of the NO signalling, ultimately resulting in the rescue of the pronephros structure. Our study provides compelling evidence that targeting NO metabolism by the administration of STS offers a promising strategy for addressing hyperglycaemia-induced organ damage. These findings underscore the potential of STS as a promising therapeutic agent for diabetic complications and warrant further investigation of its clinical applications. KEY POINTS: Sodium thiosulfate (STS) is increasingly drawing attention in research for its potential therapeutic applications across a spectrum of disease processes. Here, we demonstrate that STS treatment rescues hyperglycaemia-induced pronephros damage in zebrafish. We identified upregulation of nitric oxide signalling as the major driver behind STS-mediated rescue. Our data suggest that STS offers a promising strategy for addressing hyperglycaemia-induced organ damage, including diabetic nephropathy.

2.
Biol Reprod ; 110(4): 772-781, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38195246

ABSTRACT

Cisplatin, a platinum-containing alkylating agent, is used in the treatment of various tumors owing to its potent antitumor activity. However, it causes permanent and adverse effects, particularly hearing loss and depletion of ovarian reserve. Until recently, there were no clinically available protective agents to mitigate the adverse side effects of cisplatin-induced cytotoxicity. In 2022, sodium thiosulfate (STS) was approved by the Food and Drug Administration for mitigating hearing loss in children and adolescents undergoing cisplatin treatment. Consequently, our investigation aimed to determine if STS could protect ovarian reserve against cisplatin-induced gonadotoxicity. In an ex vivo culture, the cisplatin-only group exhibited a loss of primordial follicles, while post-STS administration after cisplatin exposure effectively protected primordial follicles. However, when post-STS was administrated either 6 or 4 h after cisplatin exposure, it did not confer protection against cisplatin-induced gonadotoxicity in postnatal day 7 or adolescent mouse models. Immunofluorescence assays using γH2AX and cPARP revealed that oocytes within primordial follicles exhibited DNA damage after cisplatin exposure, irrespective of post-STS administration. This underscores the rapid and heightened sensitivity of oocytes to gonadotoxicity. In addition, oocytes demonstrated an increased expression of pCHK2 rather than pERK, suggesting that the pathway leading to oocyte death differs from the pathway observed in the inner ear cell death following cisplatin exposure. These results imply that while the administration of STS after cisplatin is highly beneficial in preventing hearing loss, it does not confer a protective effect on the ovaries in mouse models.


Subject(s)
Antineoplastic Agents , Hearing Loss , Ovarian Reserve , Thiosulfates , Mice , Child , Female , Animals , Adolescent , Humans , Cisplatin/toxicity , Antineoplastic Agents/toxicity , Hearing Loss/chemically induced
3.
Nitric Oxide ; 149: 67-74, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38897561

ABSTRACT

Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.


Subject(s)
Hydrogen Sulfide , Signal Transduction , Thiosulfates , Thiosulfates/chemistry , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/chemistry , Humans , Animals , Signal Transduction/drug effects
4.
J Am Acad Dermatol ; 90(1): 45-51, 2024 01.
Article in English | MEDLINE | ID: mdl-37586460

ABSTRACT

BACKGROUND: Calciphylaxis is a thrombotic vasculopathy characterized by painful necrotic ulcerations. There are no Food and Drug Administration approved therapies despite high mortality. OBJECTIVE: To compare mortality and wound healing outcomes in patients treated with hyperbaric oxygen therapy (HBOT) in addition to intravenous sodium thiosulfate (IV STS) versus patients who received IV STS only. Findings were stratified by dialysis status and modality. METHODS: 93 patients were included, with 57 patients in the control group (IV STS) and 36 patients in the treatment group (HBOT + IV STS). Mortality data were analyzed with traditional survival analyses and Cox proportional hazard models. Longitudinal wound outcomes were analyzed with mixed effects modeling. RESULTS: Univariate survival analyses showed that full HBOT treatment was associated with significantly (P = .016) longer survival time. Increasing number of HBOT sessions was associated with improved mortality outcomes, with 1, 5, 10 and 20 sessions yielding decreasing hazard ratios. There was also a significant (P = .042) positive association between increasing number of HBOT sessions and increased wound score. LIMITATIONS: Data collection was retrospective. CONCLUSION: HBOT may have a role in the treatment of calciphylaxis with benefits demonstrated in both mortality and wound healing. Larger prospective studies are needed to identify which patients would most benefit from this intervention.


Subject(s)
Calciphylaxis , Hyperbaric Oxygenation , Humans , Retrospective Studies , Calciphylaxis/therapy , Calciphylaxis/drug therapy , Thiosulfates/therapeutic use
5.
BMC Nephrol ; 25(1): 26, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254024

ABSTRACT

BACKGROUND: Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification. METHODS: A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients. Then, network meta-analysis was conducted using Stata 17.0 software. RESULTS: In total, eleven RCTs including 1083 patients were qualified for this meta-analysis. We found that cinacalcet (SMD - 0.59; 95% CI [-0.95, -0.24]) had significant benefit on vascular calcification compared with conventional therapy, while sodium thiosulfate or bisphosphonates did not show such efficiency. Furthermore, as for ranking the efficacy assessment, cinacalcet possessed the highest surface under the cumulative ranking curve (SUCRA) value (88.5%) of lessening vascular calcification and was superior to sodium thiosulfate (50.4%) and bisphosphonates (55.4%). Thus, above results suggested that cinacalcet might be the most promising drug for vascular calcification treatment in hemodialysis patients. Mechanistically, our findings illustrated that cinacalcet reduced serum calcium (SMD - 1.20; 95% CI [-2.08, - 0.33]) and showed the tendency in maintaining the balance of intact Parathyroid Hormone (iPTH) level. CONCLUSIONS: This network meta-analysis indicated that cinacalcet appear to be more effective than sodium thiosulfate and bisphosphonates in mitigating vascular calcification through decreasing serum calcium and iPTH. And cinacalcet might be a reasonable option for hemodialysis patients with VC in clinical practice. SYSTEMATIC REVIEW REGISTRATION: [ http://www.crd.york.ac.uk/PROSPERO ], identifier [CRD42022379965].


Subject(s)
Diphosphonates , Thiosulfates , Vascular Calcification , Humans , Diphosphonates/therapeutic use , Cinacalcet/therapeutic use , Network Meta-Analysis , Calcium , Vascular Calcification/drug therapy , Randomized Controlled Trials as Topic
6.
Contact Dermatitis ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39340195

ABSTRACT

Gold contact allergy is diagnosed by patch testing using gold chloride or gold sodium thiosulfate. These tests often show high positivity rates, but a direct correlation with dermatitis from everyday gold exposure is rare. The aim of this study was to investigate and estimate the current prevalence of gold contact allergy in dermatitis patients. We performed a systematic literature search in PubMed, Embase and Web of Science for studies reporting the prevalence of gold contact allergy in dermatitis patients and published between January 2010 and May 2024. Data extraction and quality assessment were performed, and pooled proportions were calculated using random effects models. Sixteen studies with 14 887 dermatitis patients were included. The pooled prevalence of gold contact allergy was 14.1% (95% confidence intervals: 9.5%-19.4%) with significant heterogeneity (I2 = 98.3%). High positivity rates with limited clinical relevance highlight the need for cautious interpretation. Even within the same country, studies find different prevalence rates. Standardized testing protocols and further research are needed to better understand and manage this allergy.

7.
Int J Mol Sci ; 25(4)2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38396887

ABSTRACT

Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia-reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia-reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.


Subject(s)
Hemoglobins , Kidney Transplantation , Reperfusion Injury , Thiosulfates , Rats , Animals , Organ Preservation , Graft Survival , Rats, Inbred Lew , Kidney , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & control
8.
Int J Mol Sci ; 25(17)2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39273476

ABSTRACT

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 µM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 µM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation.


Subject(s)
Kidney Transplantation , Kidney , Reperfusion Injury , Thiosulfates , Animals , Thiosulfates/pharmacology , Thiosulfates/therapeutic use , Reperfusion Injury/drug therapy , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Rats , Male , Kidney/drug effects , Organ Preservation Solutions/pharmacology , Organ Preservation/methods
9.
J Dtsch Dermatol Ges ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39118582

ABSTRACT

Calcinosis cutis is defined as the deposition of calcium salts in the skin. The dystrophic form is the most common and usually occurs in chronic inflammatory processes associated with collagenoses. Therapeutic options include surgical excision as well as a few pharmacological treatments. Overall, the evidence for the known therapeutic interventions is very limited and there is a lack of valid recommendations. Intravenous sodium thiosulfate has been used successfully in the treatment of calciphylaxis. In our case series, five patients with dystrophic calcinosis cutis received intravenous sodium thiosulfate for at least six cycles on five consecutive days per month, with single doses of 12.5 g and 25.0 g, respectively. A reduction in the calcified lesions could not be proven with certainty, but stable disease conditions were achieved. Intravenous sodium thiosulfate may counteract the progression of calcinosis cutis. The successful use of epicutaneously applied sodium thiosulfate, as described in the literature, suggests that a higher cutaneous bioavailability can be achieved to exert a lytic effect on calcinosis cutis. This is further supported by the reported efficacy of high-dose sodium thiosulfate in the treatment of calciphylaxis.

10.
Eur J Prosthodont Restor Dent ; 32(1): 28-44, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-37463022

ABSTRACT

INTRODUCTION: This systematic review examined the effect of neutralizing agents on bond strength after irrigation with sodium hypochlorite and their existing protocols in literature. METHODS: This present study adhered to the PRISMA guidelines and was registered at PROSPERO. Five electronic databases were searched (sept-2020/jan-2021) in English, Spanish, and Portuguese, without any restrictions on publication date. Cases reports, editorials and literature reviews were not included. The risk of bias was assessed using the Cochrane Collaboration tool. From the initial 7,147 studies, 2,745 were removed as duplicates and 4,382 were excluded after a title/abstract screen. RESULTS: Seventeen in vitro studies were included. The results showed that the higher the concentration of sodium hypochlorite, the lower the bond strength at dentine/restoration interface (p⟨0.01). Among the studies, sodium ascorbate was the most widely used neutralizer and showed the most significant results in increasing bond strength (p⟨0.01). The bond strength values were found to increase with longer application time of the neutralizing substances (p⟨0.01). CONCLUSIONS: The use of sodium ascorbate as a neutralizing agent can reverse the negative effects of the sodium hypochlorite and improve the bond strength between dentine and resin cement, however, it isn't possible to determine the best protocol for use.


Subject(s)
Dental Bonding , Sodium Hypochlorite/chemistry , Sodium Hypochlorite/pharmacology , Resin Cements/chemistry , Ascorbic Acid/chemistry , Ascorbic Acid/pharmacology , Dentin , Materials Testing
11.
Angew Chem Int Ed Engl ; : e202411977, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39082829

ABSTRACT

Electrochemical sulfion oxidation reaction (SOR) offers a sustainable strategy for sulfion-rich wastewater treatment, which can couple with cathodic hydrogen evolution reaction (HER) for energy-saving hydrogen production. However, the corrosion and passivation of sulfur species render the inferior catalytic SOR performance, and the oxidation product, polysulfide, requires further acidification to recover cheap elementary sulfur. Here, we reported an amorphous high-entropy sulfide catalyst of CuCoNiMnCrSx nanosheets in situ growth on the nickel foam (CuCoNiMnCrSx/NF) for SOR, which achieved an ultra-low potential of 0.25 V to afford 100 mA cm-2, and stable electrolysis at as high as 1 A cm-2 for 100 h. These were endowed by the manipulated chemical environments surrounding Cu+ sites and the constructed "soft-acid" to "hard-acid" adsorption/desorption sites, enabling synergistically boosted adsorption/desorption process of sulfur species during SOR. Moreover, we developed an electrochemical-chemical tandem process to convert sulfions to value-added thiosulfate, providing a good choice for simultaneous wastewater utilization and hydrogen production.

12.
Biochem Biophys Res Commun ; 673: 160-168, 2023 09 17.
Article in English | MEDLINE | ID: mdl-37392479

ABSTRACT

Atopic dermatitis (AD) is a common disease with a considerable impact on the patient's quality of life and limited treatment options. Sodium thiosulfate (STS) is a traditional medicine used in the rescue of cyanide poisoning, and some pruritus dermatosis. However, the exact efficacy and mechanism of its application on AD are not clear. In this work, comparing to other traditional therapy, STS was found to effectively improve the severity of skin lesions and the quality of life in AD patients with a dose-dependent manner. Mechanically, STS downregulated the expression of IL-4, IL-13, IgE in the serum of AD patients, as well as reduce the concentration of eosinophils. Furthermore, in the AD-like mice model triggered by ovalbumin (OVA) and calcitriol, STS was found to reduce the epidermal thickness, scratching times, and the infiltration of dermal inflammatory cells in AD mice, as well as the reactive oxygen species (ROS) production and the expression levels of inflammatory cytokines in the skin tissue. In HacaT cells, STS inhibited the accumulation of ROS and activation of NLRP3 inflammasome and its downstream IL-1ß expression. Therefore, this study revealed that STS plays an important therapeutic role in AD, and the mechanism may be that STS inhibits the activation of NLRP3 inflammasome and the subsequent release of inflammatory cytokines. Thus, the role of STS in treating AD was clarified and the possible molecular mechanism was revealed.


Subject(s)
Dermatitis, Atopic , Animals , Mice , Cytokines/metabolism , Dermatitis, Atopic/pathology , Disease Models, Animal , Inflammasomes , Mice, Inbred BALB C , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Quality of Life , Reactive Oxygen Species , Skin/pathology
13.
Am J Kidney Dis ; 81(2): 232-239, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35970430

ABSTRACT

Calciphylaxis is a life-threatening complication most often associated with chronic kidney disease that occurs as a result of the deposition of calcium in dermal and adipose microvasculature. However, this condition may also be seen in patients with acute kidney injury. The high morbidity and mortality rates associated with calciphylaxis highlight the importance to correctly diagnose and treat this condition. However, calciphylaxis remains a diagnosis that may be clinically challenging to make. Here, we review the literature on uremic calciphylaxis with a focus on its pathophysiology, clinical presentation, advances in diagnostic tools, and treatment strategies. We also discuss the unique histopathological features of calciphylaxis and contrast it with those of other forms of general vessel calcification. This review emphasizes the need for multidisciplinary collaboration including nephrology, dermatology, and palliative care to ultimately provide the best possible care to patients with calciphylaxis.


Subject(s)
Calciphylaxis , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Vascular Calcification , Humans , Calciphylaxis/diagnosis , Calciphylaxis/etiology , Calciphylaxis/therapy , Vascular Calcification/etiology , Renal Insufficiency, Chronic/complications , Calcium , Obesity/complications , Kidney Failure, Chronic/therapy
14.
Pediatr Blood Cancer ; : e30550, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37416942

ABSTRACT

In two randomized trials (Children's Oncology Group ACCL0431 and International Childhood Liver Tumour Strategy Group SIOPEL-6), sodium thiosulfate (STS) demonstrated efficacy in preventing cisplatin-induced hearing loss (CIHL). However, the measures used in those trials have been superseded by the consensus International Society of Paediatric Oncology (SIOP) Ototoxicity Scale. To provide benchmark data for STS efficacy when using this contemporary scale, we reanalyzed ACCL0431 hearing outcomes with the SIOP scale and using multiple timepoints. Compared to the control arm, STS significantly reduced CIHL when assessed by the SIOP scale across these different approaches. These results provide critical data to inform treatment discussions and support future potential trial designs comparing otoprotectants.

15.
Ren Fail ; 45(2): 2254569, 2023.
Article in English | MEDLINE | ID: mdl-37755153

ABSTRACT

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.


Subject(s)
Coronary Artery Disease , Thiosulfates , Vascular Calcification , Humans , Renal Dialysis , Thiosulfates/therapeutic use , Vascular Calcification/prevention & control
16.
Ren Fail ; 45(2): 2264401, 2023.
Article in English | MEDLINE | ID: mdl-37799073

ABSTRACT

Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance.


Subject(s)
Atrial Fibrillation , Calciphylaxis , Kidney Failure, Chronic , Aged , Female , Humans , Anticoagulants , Calciphylaxis/diagnosis , Calciphylaxis/etiology , Heart Valves , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy
17.
Ren Fail ; 45(2): 2256413, 2023.
Article in English | MEDLINE | ID: mdl-37724534

ABSTRACT

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.


Subject(s)
Calciphylaxis , Kidney Failure, Chronic , Humans , Female , Calciphylaxis/etiology , Calciphylaxis/therapy , Retrospective Studies , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Calcium
18.
Int J Mol Sci ; 24(4)2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36834928

ABSTRACT

Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon's enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed.


Subject(s)
Hydrogen Sulfide , Kidney Transplantation , Reperfusion Injury , Animals , Humans , Hydrogen Sulfide/pharmacology , Kidney/pathology , Reperfusion Injury/pathology , Tissue Donors
19.
Medicina (Kaunas) ; 59(7)2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37512116

ABSTRACT

Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration (n = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration (n = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS (n = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.


Subject(s)
Calciphylaxis , Peritoneal Dialysis , Humans , Calciphylaxis/drug therapy , Calciphylaxis/etiology , Peritoneal Dialysis/adverse effects , Renal Dialysis/adverse effects
20.
J Am Acad Dermatol ; 86(5): 985-992, 2022 05.
Article in English | MEDLINE | ID: mdl-35202773

ABSTRACT

Calciphylaxis is a rare and devastating condition with important systemic ramifications. This second-part of our CME aims to educate the practicing dermatologist on the current standard of care once a diagnosis of calciphylaxis is confirmed or highly suspected. The key pathologic findings, as well as the role and limitations of biopsy, are reviewed. We aim to guide readers through the complex hospitalization and posthospitalization management of these medically vulnerable patients. Collaboration with other specialists will be discussed. Experimental and developing treatments are discussed, and the outlook of the condition is reported.


Subject(s)
Calciphylaxis , Kidney Failure, Chronic , Calciphylaxis/diagnosis , Calciphylaxis/etiology , Calciphylaxis/therapy , Female , Humans , Kidney Failure, Chronic/therapy , Male , Thiosulfates
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