Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Apr 3;6(4):e2310068.
doi: 10.1001/jamanetworkopen.2023.10068.

Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease: A Systematic Review and Meta-analysis

Wen Wen  1   2 , Ignacio Portales-Castillo  2 , Rituvanthikaa Seethapathy  2 , Olivia Durant  3 , Beza Mengesha  2 , Scott Krinsky  2 , Daniela Kroshinsky  4 , Sahir Kalim  2 , Jeremy Goverman  5 , Rosalynn M Nazarian  6 , Vipul Chitalia  7 , Rajeev Malhotra  8 , Rafael Kramann  9   10   11 , Cindy K Malhotra  12 , Sagar U Nigwekar  2
Affiliations
Meta-Analysis

Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease: A Systematic Review and Meta-analysis

Wen Wen et al. JAMA Netw Open. .

Abstract

Importance: Calciphylaxis 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.

Objective: To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.

Data sources: PubMed, 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 selection: The 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 synthesis: Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.

Main outcomes and measures: Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.

Results: Among 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 relevance: Intravenous 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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr R. Malhotra reported receiving grants from Angea Biotherapeutics and Amgen and consulting fees from Epizon Pharma, Third Pole, Myokardia (now BMS), and Renovacor outside the submitted work; in addition, he reported having a patent for pharmacologic bone morphogenetic protein inhibitors licensed to Keros Therapeutics via his home institution (Mass General Hospital). Dr Kramann reported receiving grants from Galapagos, Travere Therapeutics, Novo Nordisk, AskBio, and Chugai outside the submitted work; he reported receiving personal fees from Bayer, Eli Lilly, Grünenthal, and Pfizer outside the submitted work. Dr Nigwekar reported receiving grants from Hope Pharmaceuticals, Laboratoris Sanifit, and Inozyme Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Study Inclusion
Figure 2.
Figure 2.. The Association of Sodium Thiosulphate (STS) With Lesion Improvement and Survival Among Patients With Calciphylaxis
See this image and copyright information in PMC

References

    1. Gallo Marin B, Aghagoli G, Hu SL, Massoud CM, Robinson-Bostom L. Calciphylaxis and kidney disease: a review. Am J Kidney Dis. 2023;81(2):232-239. doi:10.1053/j.ajkd.2022.06.011 - DOI - PubMed
    1. Wen W, Portales-Castillo I, Seethapathy R, et al. . Intravenous sodium thiosulphate for vascular calcification of hemodialysis patients—a systematic review and meta-analysis. Nephrol Dial Transplant. 2022;38(3):733-745. doi:10.1093/ndt/gfac171 - DOI - PMC - PubMed
    1. Cicone JS, Petronis JB, Embert CD, Spector DA. Successful treatment of calciphylaxis with intravenous sodium thiosulfate. Am J Kidney Dis. 2004;43(6):1104-1108. doi:10.1053/j.ajkd.2004.03.018 - DOI - PubMed
    1. Kidney Disease: Improving Global Outcomes CKD-MBD Work Group . KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017;7(1):1-59. doi:10.1016/j.kisu.2017.04.001 - DOI - PMC - PubMed
    1. Sterne JA, Hernán MA, Reeves BC, et al. . ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi:10.1136/bmj.i4919 - DOI - PMC - PubMed

Publication types

Substances

LinkOut - more resources