CHARACTERIZING & ADDRESSING UNMET NEEDS IN VASCULAR CALCIFICATION & CALCIPHYLAXIS THROUGH PATIENT-ORIENTED RESEARCH

Abstract

Vascular calcification (VC) is a common complication and severe burden for patients with chronic kidney disease (CKD). It could occur within both intima and media of blood vessels, and it affects both the macrovascular and microvascular circulation. Microvascular calcification (predominantly involving subcutaneous arterioles and small vessels) that leads to vessel occlusion, tissue necrosis, and subsequent calcification of the subcutis is termed calciphylaxis. Macrovascular calcification is a strong indicator of stroke, myocardial infarction, and cardiovascular mortality. Calciphylaxis presents even more fatal with an annual mortality of 30~70%. However, there is no approved medication that can reverse or attenuate VC. Most of the conventional therapies (e.g. phosphate binders, calcimimetics, vitamin D therapy, etc.) yielded conflicting or inconclusive results. Magnesium supplementation showed attenuation on vascular calcification but needs further exploration. SNF472, as a new agent directly inhibits calcium phosphate crystal formation and aggregation, has completed a Phase 2 clinical trial showing attenuation of coronary artery and aortic valve calcification in hemodialysis patients. Sodium thiosulphate (STS) may present a plausible option for VC but with some concerns about its efficacy and safety in treating macrovascular calcification and calciphylaxis. In paper 1, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of STS for VC in CKD patients. Current evidence was synthesized and comprehensively reviewed. Furthermore, a lack of sufficient data to examine the effect of intravenous STS on calciphylaxis-associated pain has been noted. In paper 2, having seen the unmet need for clarifying the clinical significance of pain in calciphylaxis, we conducted a retrospective analysis on the pain score improvement during the first 14 days of hospitalization among patients with calciphylaxis and its associations with outcomes including lesion improvement, amputation, and survival. The association between treatments and pain improvement was also discussed.