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

Peng, Ting; Zhuo, Ling; Wang, Ying; Jun, Min; Li, Guisen; Wang, Li; Hong, Daqing

doi:10.1111/nep.13081

Cited by 103 publications

(88 citation statements)

References 44 publications

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“…The clinical characteristics at baseline were similar to those in the retrospective cohort recently described by Nigwekar et al, [16], but the mortality rate was twice as high in our patients (66 vs.35%) despite intensive care that combined sodium thiosulfate, dialysis intensification, surgical management, and/or hyperbaric oxygen therapy. Mortality was also higher than the median rate observed in published cohorts and case reports (see review by Peng et al [20]). The high death rate from cardiovascular causes (cardiac arrest or mesenteric infarction, n = 11/45, 24.5%) reflects the severity of systemic vascular disease in patients with CPX.…”

Section: Discussionmentioning

confidence: 67%

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis

Darres¹,

Delaval²,

Fournier³

et al. 2019

Dermatology

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Background: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency. Objectives: To describe the various presentations and identify predictive factors of death in patients with CPX. Methods: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days). Results: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes. Conclusions: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients.

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Section: Discussionmentioning

confidence: 67%

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis

Darres¹,

Delaval²,

Fournier³

et al. 2019

Dermatology

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“…Various modes of STS application in calciphylaxis have been reported: intravenous, intravenous during HD sessions, oral, intraperitoneal, intralesional, and topical. The optimal dose, regimen, and duration of treatment have not yet been established (4,5). Recent systematic reviews of treatment of uremic calciphylaxis with systemic STS have reported a significantly lower overall mortality rate of 38 to 50% (4, 21), compared to a 50 to 80% mortality rate after conventional treatment (8,9).…”

Section: Discussionmentioning

confidence: 99%

“…Recent systematic reviews of treatment of uremic calciphylaxis with systemic STS have reported a significantly lower overall mortality rate of 38 to 50% (4, 21), compared to a 50 to 80% mortality rate after conventional treatment (8,9). STS has several possible adverse effects, the most common ones reported being nausea, vomiting, and metabolic acidosis, followed by hypernatremia, headache, hypotension, and bone demineralization (4,22). With intra-dialytic application, a better patient survival rate and fewer problems with metabolic acidosis were reported compared to post-dialytic use (23).…”

Section: Discussionmentioning

confidence: 99%

“…With intra-dialytic application, a better patient survival rate and fewer problems with metabolic acidosis were reported compared to post-dialytic use (23). However, in a recent review, no significant difference in efficacy between intravenous, intra-dialysis, intraperitoneal, and oral STS administration was found (4). Possible adverse events should be taken into consideration when deciding how to treat a fragile ESRD patient with calciphylaxis.…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, it presents with tender erythematous papules, nodules, and plaques. Gradually, it progresses into a livedoid and stellate pattern with possible necrosis and extremely painful ulcers, predisposing the patient to infections and sepsis (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Successful treatment of extensive uremic calciphylaxis with intravenous sodium thiosulfate and its potential in treating various diseases of pathologic calcification

Burja

Jovic²,

Ekart

et al. 2019

Acta Dermatovenerologica Alpina Pannonica Et Adriatica

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A 72-year-old female patient presented with an end-stage renal disease on on-line hemodiafiltration and warfarin therapy with advanced ulcerated calciphylaxis on the lower extremities, complicated by two episodes of cellulitis. She was successfully treated for 8 months with intravenous sodium thiosulfate in combination with modification of medication and dialysis treatment, careful wound care, and other supportive measures. Calciphylaxis is an uncommon life-threatening systemic disease, mostly occurring in patients with chronic kidney disease and other risk factors. Vascular calcifications and inflammation lead to thrombotic occlusions of the cutaneous and subcutaneous arterioles, which provoke livedoid painful plaques with possible progression to necrotic ulcers. Conventional treatment is supportive. In recent decades, off-label treatment with sodium thiosulfate, a potent calcium chelator, antioxidant, and vasodilator, has been increasingly reported to be highly efficient in calciphylaxis, leading to significantly lower mortality rates. Knowledge of advancement in the treatment of calciphylaxis, which was previously a highly fatal disease, is important for physicians and other professionals from various medical fields.

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Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease

et al. 2023

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ImportanceCalciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment.ObjectiveTo perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.Data SourcesPubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction.Study SelectionThe initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided.Data Extraction and SynthesisRandom-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.Main Outcomes and MeasuresSkin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.ResultsAmong the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = −0.14; P = .008).Conclusions and RelevanceIntravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.

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

Abstract: 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.

Cited by 103 publications

References 44 publications

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis

Successful treatment of extensive uremic calciphylaxis with intravenous sodium thiosulfate and its potential in treating various diseases of pathologic calcification

Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease

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