CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 2, May – August 2024 AFRICA 121 The funnel plots exhibited symmetric patterns for the effect of intravenous STS treatment on the CACS or AACS, as shown in Fig. 11. We conducted Egger’s test to evaluate the publication bias using Stata software, which indicated no significant heterogeneity in the eight included studies. Discussion Cardiovascular calcification is much more prevalent in dialysis patients thanthosewithout chronickidneydiseaseandit contributes to extremely high morbidity and mortality rates. Control of traditional risk factors (smoking, diabetes mellitus, hypertension and dyslipidaemia) and uraemia-related cardiovascular risk factors (hyperphosphataemia, high calcium × phosphorus product, oxidative stress, systemic inflammation, protein energy wasting and so on) is essential to delay cardiovascular calcification in dialysis patients. However, even after the above treatment, there are still many patients who have increased calcification burden and even develop calcific uraemic arteriolopathy. Our results suggested that intravenous STS treatment might slow down the progression of vascular calcification compared to the control group in dialysis patients, with mild adverse effects. Micro-inflammation and oxidative stress are involved in the development of vascular calcifications.40 hsCRP is an independent risk factor for CAC initiation in dialysis patients.41 Several studies have proposed that STS might be beneficial in the remission of pathological calcifications or uraemic pruritus as a result of inflammatory or metabolic disorders.42-45 In addition to forming a chelate with calcium salts, intravenous STS could play a part through the production of hydrogen sulfide, nitric oxide synthase regeneration, endothelial warranty or equally by obstructing cell transformation.46-48 Interestingly, STS was demonstrated to restrain the osteoblastic trans-differentiation of adipocyte cells or human vascular smooth muscle cells prompted by hyperphosphataemia.47,48 These studies demonstrate the possibility of interplay between STS and factors influencing osteoblastic differentiation or those blocking calcification, such as Runx2, FGF-23 and matrix Gla protein.48,49 STS has also showed promising results in the treatment of other types of vascular calcification. For example, dystrophic vascular calcification can be associated with various autoimmune connective tissue diseases.50,51 Systemic treatment with STS might also have had positive effects on the patient’s cerebral atherosclerosis.52 Intravenous STS was reported to delay vascular calcification in dialysis patients at a dose of 25 g three times a week after dialysis, for three to six months.22 However, side effects may limit the dose and frequency of STS. The tolerated dosage and diminished patient adherence to treatment may be limited by digestive symptoms (nausea, vomiting). In addition, metabolic acidosis is often related to STS use and may be critical in some situations.18,53,54 In this meta-analysis, intravenous STS resulted in a decrease in serum bicarbonate levels, which is predictable because intravenous STS is known to cause metabolic acidosis. Dose reduction to Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Slective reporting (reporting bias) Other bias Low risk of bias Unclear risk of bias High risk of bias 0% 25% 50% 75% 100% Fig. 9. Risk-of-bias graph: review authors’ judgements about each risk-of-bias item presented as percentages across seven included RCT studies. Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Selective outcome datas (attrition bias) Selective reporting (reporting bias) Other bias Bian 2021 + + + + + + + Djuric 2019 + + + + + + + Li 2021 + + – + + + Mao 2019 + – – + + + Messa 2014 + + + + + + Saengpanit 2017 + + – + + + + Yu 2016 + – – + + + + Fig. 10. Risk-of-bias summary: review authors’ judgements about each risk-of-bias item for each included RCT study. SE(SMD) SMD –20 –10 0 10 20 0 0.5 1 1.5 2 Subgroups RCT Fig. 11. Funnel plot of the effect of changes in CACS or AACS for STS treatment versus the control group in dialysis patients with end-stage renal disease.
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