Calciphylaxis is a poorly-understood condition whose pathogenesis involves systemic calcification of arteries and arterioles. It is usually seen in patients end-stage renal disease, with an incidence of approximately 5% in dialysis patient and patients with calcium-phosphate dysregulations.1,2 However, there have also been reports of patients with biopsy-proven calciphylaxis with normal calcium-phosphate balance and renal function. We report a morbidly obese 45-year-old female with significant past medical history of necrotizing fasciitis with superimposed pseudomonas infections requiring multiple rounds of antibiotics and debridement. She presented to hospital due to chronic thigh wounds and debilitating pain. Patient developed tender and ulcerated lesions on her bilateral inner thighs spontaneously and was treated with trimethoprim-sulfamethoxazole and doxycycline. Wound cultures grew pseudomonas and Methicillin-Resistant Staphylococcus aureus. Rheumatologic work up including antinuclear antibody, rheumatoid factor, anti-double stranded DNA, anti-ribonucleoprotein and complement levels were all within normal limits except for elevated erythrocyte sedimentation rate and c-reactive protein. Patient was given multiple analgesics of which ketorolac helped the most. She was referred to dermatology after which excisional biopsy of wound was performed. Biopsy result revealed tissue necrosis and calciphylaxis. Patient was started on sodium thiosulfate (STS) infusions after discussing with dermatology and was discharged in stable conditions from hospital. The exact cause of calciphylaxis still remains unknown. It is thought to be due to intravascular calcium deposition in the media of the epidermal and subcutaneous arterioles causing medial calcification and intimal fibrosis of the arterioles resulting in thrombosis and occlusions. This leads to ischemic skin necrosis which is the most common clinical finding in calciphylaxis.3 For non-uremic calciphylaxis, there appears to be a predilection of Caucasian females, primary hyperparathyroidism, obesity, malignancy, connective tissue disease and vitamin D deficiency.4-5 Our patient had some of the risk factors including morbid obesity, middle aged Caucasian female and Vitamin D deficiency. Calciphylaxis has two-year mortality rate of 50-80% secondary to sepsis, hence preventing patients with known risk factors from developing calciphylaxis is imperative.6 The lesions of calciphylaxis are often debilitating and wound care with debridement of necrotic tissue as well as systemic antibiotics are of utmost importance, if indicated. In recent years, treatment include the use of STS, which chelate calcium from tissue deposits and bisphosphonates which are thought to help in removing arterial calcifications.7 It is important to understand that calciphylaxis may occur in patients without renal impairment and early interventions may be helpful to decrease debilitation and mortality.

Calciphylaxis is a deadly disease seen primarily in patients with end stage renal disease. Literature indicated that improved patient outcomes are seen with routine screenings. Many dialysis providers lack fundamental knowledge that would enable early identification of calciphylaxis in patients with renal disease. The purpose of this project was to design a screening instrument and develop a staff education program that would transform calciphylaxis management by promoting early identification and treatment of the disease. Knowles's theory of andragogy was used as the theoretic framework for the project. Dialysis center staff (n = 26) participated in the education. The number of participants was based on the number of staff working at the partner dialysis site. There were no exclusions as all members of the interdisciplinary team play an important role in calciphylaxis management. Surveys conducted following the education were used to determine whether dialysis staff believed they had acquired the knowledge and skills necessary to identify early signs of calciphylaxis. Descriptive data collected by the surveys indicated 60% of participants were not at all comfortable identifying patients at risk for developing calciphylaxis prior to attending the education presentation. Following the presentation, 68% of participants felt very comfortable identifying at-risk patients, an increase of 82.3%. This project exemplified that calciphylaxis detection is a secondary prevention nursing intervention that has potential for promoting positive social change by improving patient outcomes, reducing mortality rates in the end stage renal disease population, and providing empirical data to inform evidence-based therapies for at-risk patients.

Calciphylaxis is a late complication of end-stage renal disease (ESRD) affecting ~1–4% patients on hemodialysis, with a mortality rate of >50%. Cutaneous manifestations include necrotic, non-healing ulcers most commonly in the lower extremities. Visceral organ vasculopathy often occurs as well. Warfarin is a possible risk factor due to its effect on the inhibition of Matrix GLa protein. Under the influence of hyperphosphatemia, vascular smooth muscle cells can undergo ectopic calcification in absence of the MGLa protein. The issue of anticoagulation in dialysis patients has therefore been debated, as Warfarin may potentially induce vasculopathy and increase risk of bleeding, such as hemorrhagic strokes and GI bleeds. A 64-year-old male with ESRD, non-compliant with dialysis, presented with lower extremity pain. Patient was noted to have large, malodorous, bilateral lower extremity ulcers with necrosis and eschars. Punch biopsy of the ulcers demonstrated acute inflammation with calcium deposits and thrombi within the blood vessels, suggestive of Calciphylaxis. Patient was started on Sodium Thiosulfate and Sevelamer for hyperphosphatemia. Atrial fibrillation was incidentally found on EKG, and due to high risk of stroke based on the CHA2DS-VASc score, patient was started on Heparin and bridged to Warfarin on discharge. Patient was readmitted 3 months later to the ICU with septic shock. Lower extremity ulcers appeared to be healing, but he reported several episodes of hematochezia (INR=2.0, hemoglobin=5.2). Warfarin was therefore held and patient was transfused. EGD showed no evidence of upper GI bleed, however patient refused colonoscopy. Patients on dialysis are at increased risk of bleeding due to defective primary hemostasis. The most serious source of bleeding is gastrointestinal, which accounts for 3–7% of all deaths in the dialysis population. Current guidelines for management of atrial fibrillation by the American Heart Association recommend warfarin for oral anticoagulation in patients with ESRD who have a CHA2DS2-VASc score of 2 or greater to prevent thromboembolic events. Our patient with ESRD and Calciphylaxis presented with new-onset atrial fibrillation and therefore started on Warfarin due to high CHA2DS2-VASc score. However patient developed a GI bleed with worsening anemia requiring transfusion, prompting discontinuation of Warfarin. It is therefore questionable whether the risk-benefit assessment based on CHA2DS2-VASc is appropriate for dialysis patients. Unfortunately, all the data available on the subject of Warfarin in ESRD patients are observational without any randomized-clinical trials. Therefore no objective criteria exist to modify the anticoagulation guidelines in dialysis patients.

This thesis explores the pathogenesis of calciphylaxis, a rare and potentially fatal complication of chronic kidney disease (CKD) characterized by calcification and thrombosis of small- to medium-sized arteries. A range of bench techniques, including cell culture, genetic analysis, and immunofluorescence, were utilized in combination with human samples from patients with calciphylaxis and healthy controls. The results revealed a pathway that may modulate the thrombotic phenotype in these patients and, in turn, may serve as a targetable therapeutic axis. This work provides a foundation for further research and clinical advances in the field of calciphylaxis. Moreover, this study has the potential to inform the development of therapeutic interventions that could greatly improve the outcomes of CKD patients suffering from calciphylaxis. / 2026-03-05T00:00:00Z