Non-chronic kidney disease-induced calciphylaxis: a rare case report.

Calciphylaxis is a disorder causing ischemic skin necrosis, typically associated with end-stage renal disease or those receiving dialysis. Occurrence is rare in those without end-stage renal disease, and treatment options are limited. This case report describes a patient with calciphylaxis without end-stage renal disease or history of dialysis. Treatment with sodium thiosulfate, a first line option, had to be stopped due to metabolic derangements, limiting the healing process. Diagnosis and treatment of this rare disorder are important to prevent further complications that may result.

Clinical characteristics and treatment modalities in uremic and non uremic calciphylaxis - a dermatological single-center experience.

Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations. Although calciphylaxis is frequently seen in patients with end-stage kidney disease on dialysis (calcific uremic arteriolopathy, CUA), there are reported cases of nonuremic calciphylaxis (NUC), which often remain undiagnosed. We conducted a retrospective chart review at our dermatological hospital and evaluated data concerning the epidemiology, comorbidities, medication, laboratory abnormalities, and therapeutic approaches of 60 patients diagnosed with calciphylaxis between 01/2012 and 12/2022. We identified 21 patients diagnosed with NUC and 39 with kidney disease. The predilection sites of skin lesions were the lower legs in 88% (n = 53), followed by the thigh and gluteal regions in 7% (n = 4). Significant differences were identified in comorbidities, such as atrial fibrillation (p < 0.001) and hyperparathyroidism (p < 0.01) accounting for CUA patients. Medication with vitamin K antagonists (p < 0.001), phosphate binders (p < 0.001), and loop diuretics (p < 0.01) was found to be associated with the onset of calciphylaxis. Hyperphosphatemia (p < 0.001), increased parathyroid hormone (p < 0.01) and triglyceride levels (p < 0.01), hypoalbuminemia (p < 0.01) and decreased hemoglobin values (p < 0.001) in the CUA cohort were significantly different from those in the NUC group. All patients with CUA received systemic medication. In contrast, only 38% (n = 8) of patients with NUC received systemic treatment. Striking discrepancies in the treatment of both cohorts were detected. In particular, NUC remains a disease pattern that is still poorly understood and differs from CUA in several important parameters.

Profound metabolic acidosis in association with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy: a case report and literature review.

Calciphylaxis, also known as Calcific uremic arteriolopathy (CUA), is a serious disorder that presents with skin necrosis due to calcification of dermal and subcutaneous adipose tissue capillaries and arterioles. The condition occurs primarily in patients with end-stage renal disease (ESRD) on dialysis, and it carries high morbidity and mortality, primarily due to sepsis, with an estimated six-month survival of approximately 50%. Although there are no high-quality studies to guide the optimal treatment approach for patients with calciphylaxis, many retrospective studies and case series support treatment with sodium thiosulfate (STS). Despite the frequent use of STS as an off-label treatment, data regarding its safety and efficacy are limited. STS has generally been considered a safe drug with mild side effects. However, severe metabolic acidosis associated with STS is a rare and life-threatening complication of STS treatment and is often unpredictable. Herein, we report a 64-year-old female with ESRD on peritoneal dialysis (PD) who presented with a profound high anion gap metabolic acidosis and severe hyperkalemia while on STS treatment for CUA. No other etiology for her severe metabolic acidosis other than STS was identified. ESRD patients receiving STS should be monitored closely for this side effect. Dose reduction, increasing the duration of infusion, or even discontinuing STS treatment should be considered if severe metabolic acidosis develops.

Calcific Uremic Arteriolopathy in End-Stage Renal Disease: A Rare Life-Threatening Condition.

Calcific uremic arteriolopathy, or calciphylaxis, is a highly morbid, life-threatening syndrome of microvascular calcification leading to progressive skin necrosis. It affects 1-4% of the population with end-stage renal disease (ESRD) and is rarely seen in other conditions. The one-year mortality rate is 80% for patients with ulcerations. There is no evidence-based treatment, and the response to therapy is poor; thus, it creates a serious therapeutic challenge for clinicians. Our aim is to discuss a diagnostic approach and management of calciphylaxis and to raise awareness about this condition among the medical community. We are describing a case of calciphylaxis in a 68-year-old female with a past medical history of ESRD on hemodialysis, who presented with altered mental status and painful ulcers on her feet and thighs. The patient was admitted for acute encephalopathy due to sepsis secondary to a urinary tract infection (UTI) versus permacath-related bacteremia versus wound infection of pressure ulcers on the lower extremities. Broad-spectrum antibiotics were started. Computed tomography (CT) of bilateral thighs with contrast showed extensive arterial calcifications, characteristic of calciphylaxis. Nephrology recommended sodium thiosulfate with each hemodialysis session. Vitamin D and iron were discontinued. Despite therapy, the wound significantly progressed within the next eight weeks, leading to mortality due to sepsis. In conclusion, calcific uremic arteriolopathy is a challenging disease with a poor prognosis. Early diagnosis is crucial, so aggressive therapy can be started immediately. A multidisciplinary approach may improve survival in cases of calciphylaxis. More studies are needed to improve the diagnostic approach and medical management of the disease.

Calciphylaxis: A Rare Complication With a Fatal Outcome in End-Stage Renal Disease.

Calciphylaxis, or calcific uremic arteriolopathy, is a rare and deadly disease that affects patients with end-stage renal disease (ESRD). It typically manifests in the abdomen and lower extremities. We present a case of a 59-year-old female patient on dialysis due to ESRD who complained of a three-week history of hemorrhagic and painful bilateral lower limb lesions. The predominant clinical suspicion was warfarin-induced skin necrosis (WISN); however, the persistence of unresolved skin lesions post-warfarin cessation generated the impression of calciphylaxis. A skin biopsy confirmed the classical histological findings associated with calciphylaxis. This paper highlights the possible importance of warfarin being an inciting event, as well as the early differentiation between the presentations of WISN and calciphylaxis.

Uremic Bilateral Breast Calciphylaxis: A Case Report and Literature Review.

Calciphylaxis, also called calcific uremic arteriolopathy, is a rare benign cutaneous manifestation. Although little is known about its pathogenesis, it is thought to be a result of vascular wall calcification leading to soft tissue necrosis, and it is usually encountered in patients with end-stage kidney disease (ESKD) on long-term renal dialysis. Breast calciphylaxis is a rare entity that may present as a breast mass or necrotic ulcers, and it is common for it to be initially mistaken for a malignant breast pathology. In this article, we present a case of bilateral breast calciphylaxis in a 66-year-old female with ESKD receiving long-term dialysis.

Calciphylaxis Secondary to Vitamin D Supplementation.

Calciphylaxis is a rare cutaneous disease consisting of purpuric and necrotic lesions, and it affects mostly patients with renal failure. More rarely, it can be observed in patients with preserved renal function, acquiring the name of non-uremic calciphylaxis (NUC). Although its pathophysiology is under uncertainty, many etiological factors have been implicated. This report describes a patient who developed NUC, possibly triggered by vitamin D supplementation.

Multimodality approach to treat calciphylaxis in end-stage kidney disease patients.

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.

Cutaneous vascular calcifications in patients with chronic kidney disease and calcific uremic arteriolopathy: a cross-sectional study.

INTRODUCTION: Calcific uremic arteriolopathy is a life-threatening cutaneous condition in patients with chronic kidney disease. Often, clinical diagnosis is accompanied by histopathologic evaluations demonstrating vascular calcium deposits. We aimed to investigate the presence of cutaneous calcifications in non-lesional tissue in patients with chronic kidney disease, and the relation to systemic vascular calcification. METHODS: We investigated the presence of cutaneous vascular calcifications in non-lesional skin biopsies from patients with current or previous calcific uremic arteriolopathy and patients with different stages of chronic kidney disease without calcific uremic arteriolopathy, and explored their association with vascular calcification in other vascular beds. Systemic vascular calcification was examined by mammography and lumbar X-ray. RESULTS: Thirty-nine adults were enrolled (current or previous calcific uremic arteriolopathy, n = 9; end-stage chronic kidney disease, n = 12; chronic kidney disease stage 3b-4, n = 12; healthy controls, n = 6). All calcific uremic arteriolopathy patients had end-stage kidney disease. Cutaneous vascular calcifications were not present in any of the non-lesional skin punch biopsies. Breast arterial calcification was demonstrated in patients with calcific uremic arteriolopathy (75%) and chronic kidney disease (end-stage 67% and stage 3b-4 25%, respectively), but in none of the controls. All chronic kidney disease patients had systemic calcification on lumbar X-ray (median score 21, 22, and 15 in patients with calcific uremic arteriolopathy, end-stage kidney disease and chronic kidney disease stage 3b-4). The serum calcification propensity was significantly different between groups. DISCUSSION: Despite a high burden of systemic vascular calcification, cutaneous calcium deposits in non-lesional tissue could not be demonstrated histopathologically in patients with chronic kidney disease (with or without current or previous calcific uremic arteriolopathy). Further studies to determine whether these findings are representative or attributed to other factors are warranted.

Sodium Thiosulfate for Calciphylaxis Treatment in Patients on Peritoneal Dialysis: A Systematic Review.

Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration (n = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration (n = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS (n = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.

Penile calciphylaxis with penoscrotal necrosis: A case report with literature review.

Penile calciphylaxis, also known as calcific uremic arteriolopathy is an uncommon condition of the penile vessels due to its extensive vascular network. The aim of this report is to report a very rare case of penile calciphylaxis with penoscrotal necrosis. A 54-year-old male patient presented with progressive penoscrotal necrosis within a duration of one month. He had a history of diabetes mellitus and stage 5 chronic kidney disease. Under spinal anesthesia, partial penectomy and excision of the necrotic scrotum were performed. Histopathological examination was consistent with calciphylaxis. Despite it is a rare occurrence, penile calciphylaxis should be included in the different diagnosis of any diabetic and end stage kidney disease patients who presented with penile pain.

Calciphylaxis and Kidney Disease: A Review.

Calciphylaxis is a life-threatening complication most often associated with chronic kidney disease that occurs as a result of the deposition of calcium in dermal and adipose microvasculature. However, this condition may also be seen in patients with acute kidney injury. The high morbidity and mortality rates associated with calciphylaxis highlight the importance to correctly diagnose and treat this condition. However, calciphylaxis remains a diagnosis that may be clinically challenging to make. Here, we review the literature on uremic calciphylaxis with a focus on its pathophysiology, clinical presentation, advances in diagnostic tools, and treatment strategies. We also discuss the unique histopathological features of calciphylaxis and contrast it with those of other forms of general vessel calcification. This review emphasizes the need for multidisciplinary collaboration including nephrology, dermatology, and palliative care to ultimately provide the best possible care to patients with calciphylaxis.

Perioperative Management of Calciphylaxis: Literature Review and Treatment Recommendations.

Calciphylaxis is a serious and rare medical condition that leads to substantial clinical manifestations including pain, creating perioperative and treatment challenges. No standard treatment protocol exists nor are comprehensive guidelines available for perioperative management of patients with calciphylaxis. In this review, we evaluate existing literature (January 2000 to May 2021) with the aim to offer guidance for treating patients with this challenging disease through the perioperative period. Although no therapies are currently considered standard for treating calciphylaxis, multiple interventions are available for improving symptoms. Preoperative and intraoperative management involves monitoring and optimizing patient comorbid conditions and any possible electrolyte imbalances. Postoperative management can be challenging when potential calciphylaxis triggers are indicated, such as warfarin and corticosteroids. In addition, poor wound healing and difficult pain control are common. Therefore, a multifactorial approach to controlling postoperative pain is recommended that includes the use of nerve blocks, renal-sparing opioids, benzodiazepines, and/or ketamine. We present preoperative, intraoperative, and postoperative recommendations for treating calciphylaxis with levels of evidence when appropriate.

A Fatal Case of Penile Calciphylaxis.

Calciphylaxis is a rare and serious complication of chronic renal failure characterized by vascular calcium overload. It has a high mortality rate. Penile calciphylaxis is an extremely rare condition of penile necrosis due to calciphylaxis of the penile arterioles. Presented here is a severe case of systemic calciphylaxis initially presented as penile necrosis treated with sodium thiosulfate and amputation.

A Scoping Review of Alternative Anticoagulation Strategies for Hemodialysis Patients with a Mechanical Heart Valve.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have high rates of cardiac valvulopathy but can develop contraindications for vitamin K antagonist (VKA) therapy. We explored the evidence for alternative anticoagulation strategies in patients with ESRD with a contraindication for VKA therapy. METHODS: A scoping review was completed, searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Conference abstracts from inception to March 30, 2021. The study population was patients with ESRD who were on VKA therapy and developed a contraindication to VKA therapy use. All data regarding studies, patient characteristics, anticoagulation strategy, and clinical outcomes were summarized. RESULTS: Twenty-three articles met inclusion criteria. These articles included 57 patients. Contraindications to VKA therapy included calcific uremic arteriolopathy (CUA) (n = 55) and warfarin-induced skin necrosis (n = 2). All studies were either case reports or case series. There were 10 anticoagulation strategies identified. Continuation of VKA therapy was associated with increased death and decreased rates of CUA resolution (80.0% and 10.0%, respectively), compared to apixaban (24.0% and 70.8%), subcutaneous (SC) low-molecular-weight heparin (LMWH) (14.3%, 85.7%), and SC unfractionated heparin (0.0%, 100.0%). While only 5 patient cases were reported with mechanical heart valves, SC LMWH use has been reported in this context with good outcomes. CONCLUSIONS: In patients with ESRD who develop a contraindication to VKA therapy, several alternative anticoagulation strategies have been reported with superior outcomes to VKA continuation. While outcomes appear superior to continuation of VKA therapy, more data are required before definitive recommendations can be made for the patient with ESRD and a mechanical heart valve.

Nonuremic Calciphylaxis Associated With Hypercalcemia and Rheumatologic Diseases.

Calcific uremic arteriolopathy, termed calciphylaxis, was previously considered a condition that developed mostly in patients requiring dialysis. It has now been described in kidney transplant patients, in advanced chronic kidney disease (CKD) patients not requiring dialysis, and in individuals with maintained kidney function. We describe an individual with CKD stage 3b with hypercalcemia who presented with features highly specific for calciphylaxis based on results of a skin biopsy. The condition has high morbidity and mortality, and thus prompts immediate cessation of the offending agents or treatment of the cause. The following case and literature review demonstrates a need for a detailed assessment of patients' risks and exposures and expanding the differential diagnosis to include calciphylaxis in nonuremic patients with necrotic ulcers with a plan for early imaging and possible biopsy.