Risk Factors Associated With the Development of Calciphylaxis in Patients With Chronic Kidney Disease: A Systematic Review.

Calciphylaxis is a rare but potentially life-threatening disease that is not yet completely understood. It occurs mainly in patients with chronic kidney disease termed calcific uremic arteriolopathy (CUA) but also affects patients with normal renal function. Although this disease's pathogenesis is unclear, it is associated with the dysregulation of calcium and phosphate and subsequent calcification of peripheral arterioles. Calciphylaxis has up to 80% mortality, even with multidisciplinary and multimodal treatment modalities. The available literature identified some relevant risk factors associated with the development of calciphylaxis, but the authors differ significantly in risk profiling. Moreover, most papers on calciphylaxis are observational studies, namely case series, case reports, cohort, and cross-sectional studies. Although recently available articles mentioned some risk factors, the studies mainly focused on diagnosis, treatment, and prognosis with limited emphasis on structured risk profiling. In addition, experimental and systemic review studies on risk factors associated with calciphylaxis are lacking. Thus, this systematic review's primary focus is to determine risk factors associated with developing calciphylaxis in patients with chronic kidney disease. We searched electronic databases from 2018 to 2024 for articles that contained relevant risk factors linked with the development of calciphylaxis using the keywords calciphylaxis, chronic kidney disease, and risk factors. We identified 486 articles, removed duplicate papers from selected articles, applied inclusion and exclusion criteria, and conducted a quality assessment test. Two independent authors performed data extraction manually, and we compared the results for consistency and accuracy. Twenty-two articles met the eligibility criteria, but only 16 articles passed the quality assessment appraisal and were included in the systematic review. We identified 1,739 patients: 664 (38.2%) and 1075 (61.81%) were males and females, respectively. A total of 1373 (78.95%) were on dialysis, and 926 (53.25%) were diabetics. Caucasians and patients with obesity were 695 (37.90%) and 613 (35.25%), respectively. At the time of diagnosis, 599 (34.45%), 311 (17.90%), and 278 (15.99%) were on vitamin K antagonists (VKA), vitamin D, and calcium phosphate binders. The number of patients with elevated parathyroid hormone was 196 (11.27%). Our study found no experimental or systematic reviews that primarily focused on risk factors associated with the development of calciphylaxis. Our research indicated that dialysis is the most frequent risk factor linked to the development of calciphylaxis. Other risk factors include being caucasian, female gender, obese, diabetic mellitus (DM), having elevated parathyroid hormone, and use of VKA (warfarin), vitamin D, and calcium phosphate binders. These findings are consistent with the evidence seen in most of the articles we reviewed. However, the papers we studied are mainly observational mono-centered research articles, with the majority having a small sample size. Thus, we recommend a multicenter, large-scale experimental study to assess risk factors and profiling for the development of calciphylaxis in patients with chronic kidney disease.