Calciphylaxis Beyond Dialysis: Real-World Comparative Analysis of Outcomes in ESRD and Advanced Nondialysis-Dependent CKD

Background: Calciphylaxis is classically linked to end-stage renal disease (ESRD) requiring dialysis, but increasing reports describe its occurrence in patients with advanced non-dialysis chronic kidney disease (CKD). However, comparative incidence and outcomes in these populations remain poorly characterized in large real-world datasets. Methods: We queried the TriNetX Global Collaborative Network, which includes data from 148 healthcare organizations, to identify adults (≥18 years) with either: Cohort A: ESRD receiving dialysis Cohort B: Stage 4–5 CKD not on dialysis between 2005 and 2025. Calciphylaxis was identified using ICD-10 code E83.59. Patients were followed for one year after diagnosis for outcomes including all-cause mortality, limb amputation, and sepsis. Risk ratios (RR), odds ratios (OR), and Kaplan-Meier survival analyses were conducted without propensity matching. Results: We identified 503,864 patients with ESRD and 685,346 with stage 4–5 CKD not on dialysis. Calciphylaxis was diagnosed in: 1.5% of ESRD patients vs. 0.5% of non-dialysis CKD patients RR: 3.25; OR: 3.28; p<0.001 Following calciphylaxis diagnosis: Mortality was high in both groups Amputation occurred in 1.4% (ESRD) vs. 0.4% (CKD); OR: 3.27 Sepsis occurred in 19.3% (ESRD) vs. 12.3% (CKD); OR: 1.71 Kaplan-Meier curves showed significantly lower event-free survival in the ESRD cohort, but the non-dialysis CKD group also experienced substantial morbidity and mortality. Conclusion: Calciphylaxis is not limited to dialysis-dependent individuals. While less frequent in patients with non-dialysis advanced CKD, outcomes including mortality, infection, and limb loss remain severe. These findings underscore the need for increased awareness, early recognition, and preventive efforts in high-risk CKD populations irrespective of dialysis status.