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Case Report: This report describes a patient who developed calciphylaxis, a rare complication of end-stage renal disease (ESRD) associated with high mortality. The patient is a 48-year-old female who presented to the emergency department (ED) with altered mental status, metabolic acidosis, hypotension, bradycardia, and weakness secondary to missing several hemodialysis sessions. Her past medical history is significant for ESRD, peripheral vascular disease (PVD), atrial fibrillation, chronic pain, diabetes mellitus II (DMII), and hypertension (HTN). Upon examination, patient denies chest pain and no changes were noted in the electrocardiogram (ECG). A venous blood draw revealed β-naturetic peptide (BNP) 1,679, anion gap (AG) 26, potassium 6.1, creatinine 7.0, and lactate 9.57. Arterial blood gas (ABG) revealed pH 7.1, partial pressure of carbon dioxide (pCO2) 43.6, partial pressure of oxygen (pO2) 31, and bicarbonate (HCO3) 16.9. In the ED, the patient received dopamine, atropine, fluids, and HCO3. After a consultation with pulmonology and nephrology, the patient was admitted to the intensive care unit (ICU) for management of her acute symptoms. On day 3 of admission, she was transferred to the floor for further care. In addition to her acute symptoms, the patient presented with multiple chronic, necrotic lesions on her lower extremities. Patient exhibited an active wound on her right great toe while the second and third toes were necrotic. A developing lesion was also noted on her right inner thigh that was tender, indurated, and erythematous. Wounds were biopsied and debrided on day 3 and were confirmed to be calciphylaxis by pathology. Repeat biopsy and debridement were conducted on day 8 of admission. On the same day, the patient was started on sevelamer 2,400 mg three times daily and sodium thiosulfate 25g three times weekly after dialysis for treatment of her wounds. On day 10, patient also started hyperbaric oxygen (HBO) therapy with a total of 15 treatments planned. On day 27, the patient underwent additional debridement and wounds were swabbed and cultured, revealing growth of Stenotrophomonas maltophilia, Enterobacter cloacae, and Candida parapsilosis. Patient was treated for her infection with a 14-day regimen of sulfamethoxazole-trimethoprim (SMX-TMP) 2.5 mg/kg every 24 hours (Q24H) and fluconazole 100mg once daily. Patient received a total of 11 inpatient HBO treatments; subsequent treatments were discontinued due to patient’s intolerance to pain and lack of improvement in wound healing. Patient remained on sevelamer and sodium thiosulfate for management of calciphylaxis. Additionally, she was put on a schedule of twice weekly surgical debridement and dressing changes to facilitate healing of her wounds. After a two-and-a-half month stay at the hospital, patient was discharged to a long-term acute care (LTAC) facility to continue treatment for her lesions. Calciphylaxis is a rare and serious complication found in patients with kidney disease, more common in ESRD and after kidney transplantation. Case reports have been described in primary literature, but data is limited regarding effective therapeutic strategies, and the pathophysiology of the disease is poorly understood. There are no published guidelines detailing the diagnosis and treatment of calciphylaxis. Commonly, treatment involves both surgical and medical modalities.