THE LIFESAVING JOURNEY FOR CALCIPHYLAXIS: ADDRESSING RAPIDLY PROGRESSIVE ATTACKS WITH MULTIDIMENSIONAL AND AI RESEARCH FOR REGENERATIVE MEDICINE

Introduction:

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), primarily occurs in patients with chronic kidney disease (CKD). It is an orphan disease characterized histologically by microarteriolar calcification, fibrosis, and thrombosis mainly in subcutaneous tissue. Skin biopsy is the gold standard for diagnosis, but it is invasive. The scarcity of animal models that mimic the clinical presentation hampers in-depth investigation. Until now, the multidisciplinary targeted approach has been the primary method of treatment with no proven therapy, resulting in a one-year mortality rate of up to 80% due to ulceration and infection. There is an urgent need for education, explorating new avenues of its mechanisms, precise diagnostic, and therapeutic measures.

Methods:

CKD-mineral and bone disorder (CKD-MBD), particularly vascular calcification, shares certain similarities with calciphylaxis in terms of risk factors, pathogenesis, and treatment methods. In light of this, we have compiled an article collection (AC) titled “Calciphylaxis and CKD-MBD: Ongoing Challenges and Opportunities” in the Journal of Renal Failure, which can be viewed at: https://www.tandfonline.com/journals/irnf20/collections/calciphylaxis-mineral-bone-disease. Seventeen manuscripts have been included, with 5 focused on calciphylaxis and 12 on CKD-MBD. The authors come from China, Canada, and Germany.

Results:

 A series of studies in this AC has yielded critical findings on calciphylaxis and CKD-MBD, related cardiovascular events, and therapeutic strategies. However, vascular calcification, which is a common complication in CKD patients, cannot completely explain the rapid progression of calciphylaxis and its dangerous prognosis. Elaborating on the acute impacts on progressive vascular injury, including the induction of severe ischemia and inflammatory responses, has been emphasized as key factors associated with skin tissue necrosis and life-threatening infections. Due to the heterogeneity of the clinical manifestations of calciphylaxis, there is an urgent need to explore non-invasive biomarkers and foster collaboration among multiple centers and disciplines.  Actively listening to the voices of patients and their families will shed light on our understanding of early diagnosis, disease progression, treatment response, and research directions. Monotherapy for calciphylaxis poses challenges. Exploring safe, effective, economical, and accessible treatment strategies, such as stem cells therapy, holds promising prospects. Building a multiomics and multidimensional research system with artificial intelligence (AI) technologies, based on the specific molecular makeup of calciphylaxis patients, will advance our understanding and tailor regenerative treatment strategies for this devastating disease (Fig. 1).

Fig. 1. Lifesaving journey of calciphylaxis to regenerative medicine.

Conclusions:

The investigation of ischemia and inflammation in calciphylaxis should be prioritized. Patients and their families are essential members to inform the research agenda. Embracing new technologies, constructing non-invasive diagnostic and early prediction models, identifying treatment targets through multidimensional research, and promoting regenerative medicine under the guidance of biomarkers are the North Star in the person-centered lifesaving journey for calciphylaxis.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.