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American Journal of Kidney Diseases :... Jul 2015Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many... (Review)
Review
Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. It is predominantly seen in patients with chronic kidney failure treated with dialysis (uremic calciphylaxis) but is also described in patients with earlier stages of chronic kidney disease and with normal kidney function. In this review, we discuss the available medical literature regarding risk factors, diagnosis, and treatment of both uremic and nonuremic calciphylaxis. High-quality evidence for the evaluation and management of calciphylaxis is lacking at this time due to its rare incidence and poorly understood pathogenesis and the relative paucity of collaborative research efforts. We hereby provide a summary of recommendations developed by a multidisciplinary team for patients with calciphylaxis.
Topics: Animals; Arterioles; Biopsy; Calciphylaxis; Case-Control Studies; Chronic Kidney Disease-Mineral and Bone Disorder; Combined Modality Therapy; Comorbidity; Diabetic Nephropathies; Disease Models, Animal; Electrolytes; Fatal Outcome; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Malnutrition; Middle Aged; Obesity; Pain Management; Rats; Risk Factors; Shock, Septic; Skin; Thiosulfates; Uremia; Vitamin D Deficiency; Wound Healing
PubMed: 25960299
DOI: 10.1053/j.ajkd.2015.01.034 -
Current Opinion in Nephrology and... Jul 2017Calciphylaxis remains a poorly understood vascular calcification disorder with predilection for patients with end-stage renal disease (ESRD). Recent data from large... (Review)
Review
PURPOSE OF REVIEW
Calciphylaxis remains a poorly understood vascular calcification disorder with predilection for patients with end-stage renal disease (ESRD). Recent data from large patient registries and databases have begun to provide information regarding incidence, risk factors, and outcomes in patients with calciphylaxis.
RECENT FINDINGS
The most recent estimate places the incidence of calciphylaxis at 3.5 new cases/1000 patient-years among the patients with ESRD on chronic hemodialysis. It is possible that misdiagnosis or subclinical disease may attribute to lower than the true incidence. There is a suggestion that the incidence is higher in peritoneal dialysis patients compared with patients with hemodialysis. Recent studies have identified a number of risk factors and point to the effects of vitamin K deficiency mediated impairment in Matrix Gla Protein carboxylation as one of the likely pathogenic mechanisms. The outcomes in calciphylaxis patients remain poor with mortality approaching 30% at 6 months and 50% at 12 months.
SUMMARY
The present review describes recent literature in the field of calciphylaxis. Calciphylaxis registries and specimen biorepositories promise to provide insights into the pathogenesis of calciphylaxis and will pave the way for much needed clinical trials.
Topics: Calciphylaxis; Humans; Incidence; Kidney Failure, Chronic; Prognosis; Registries; Renal Dialysis; Risk Factors; Vascular Calcification
PubMed: 28375870
DOI: 10.1097/MNH.0000000000000328 -
Journal of Family Medicine and Primary... Sep 2019Calciphylaxis also known as Calcific uremic arteriolopathy (CUA), is a rare fatal complication usually associated with end-stage renal disease (ESRD). It is... (Review)
Review
Calciphylaxis also known as Calcific uremic arteriolopathy (CUA), is a rare fatal complication usually associated with end-stage renal disease (ESRD). It is characterized by skin ulceration and necrosis leading to significant pain. The disease calciphylaxis is pathological state resulting in accumulation of calcium content in medial wall of small blood vessels along with the fibrotic changes in intima. The aetiopathogenesis of this disease, small vessel vasculopathy, remains complicated, and unclear. It is believed that development of calciphylaxis depends on medial calcification, intimal fibrosis of arterioles and thrombotic occlusion. The disease is rare, life-threatening medical condition that occurs mostly in population with kidney disease or in patients on dialysis. Skin biopsy and radiographic features are helpful in the diagnosis of calciphylaxis, but negative results do not necessarily exclude the diagnosis. This article highlights steps undertaking in the diagnosis of calciphylaxis.
PubMed: 31681640
DOI: 10.4103/jfmpc.jfmpc_588_19 -
JAMA Network Open Apr 2023Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment.
OBJECTIVE
To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.
DATA SOURCES
PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction.
STUDY SELECTION
The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.
MAIN OUTCOMES AND MEASURES
Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.
RESULTS
Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P = .008).
CONCLUSIONS AND RELEVANCE
Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.
Topics: Adult; Humans; Male; Middle Aged; Female; Calciphylaxis; Retrospective Studies; Bayes Theorem; Renal Insufficiency, Chronic
PubMed: 37099293
DOI: 10.1001/jamanetworkopen.2023.10068 -
Actas Dermo-sifiliograficas Dec 2015Calcinosis cutis (CC) is defined as the deposition of calcium salts in the skin. The condition is divided into 5 types: calciphylaxis and dystrophic, metastatic,... (Review)
Review
Calcinosis cutis (CC) is defined as the deposition of calcium salts in the skin. The condition is divided into 5 types: calciphylaxis and dystrophic, metastatic, idiopathic, and iatrogenic CC. Dystrophic CC is the most common form and usually occurs in association with autoimmune diseases. CC can be treated surgically or with the use of drugs such as diltiazem, bisphosphonates, warfarin, ceftriaxone, probenecid, minocycline, or aluminum hydroxide. Calciphylaxis is defined as calcification of the media of small- and medium-sized blood vessels in the dermis and subcutaneous tissue. Clinically, calciphylaxis causes livedo racemosa, which progresses to retiform purpura and skin necrosis. First-line treatment is with sodium thiosulfate. We present a review of the calcifying disorders of the skin, focusing on their diagnosis and treatment.
Topics: Autoimmune Diseases; Calcinosis; Calciphylaxis; Calcium; Collagen Diseases; Diagnostic Imaging; Humans; Iatrogenic Disease; Phosphorus; Skin Diseases; Skin Diseases, Parasitic; Thiosulfates
PubMed: 26394755
DOI: 10.1016/j.ad.2015.09.001 -
Iranian Journal of Kidney Diseases May 2014Calciphylaxis is characterized by calcification and thrombosis of arteries resulting in ischemic necrosis of predominantly skin and subcutaneous tissue. Primarily...
Calciphylaxis is characterized by calcification and thrombosis of arteries resulting in ischemic necrosis of predominantly skin and subcutaneous tissue. Primarily affecting patients with end-stage renal disease, calciphylaxis is diagnosed rarely in the absence of renal replacement therapy. We report an elderly obese woman presented with leg pain and ulceration. She had chronic kidney disease, diabetes mellitus, hypertension, and peripheral vascular disease. Angiography revealed occlusion of the left superficial femoral, popliteal, and distal tibial arteries. Amputation was performed. Histological examination demonstrated medial calcification, intimal hyperplasia, and thrombosis of small- and medium-sized arteries in the subcutaneous tissue. This case features calciphylaxis in a patient with chronic kidney disease before the onset of uremia. Calciphylaxis and atherosclerotic peripheral vascular disease have several risk factors in common. This report calls attention to a disorder that can be masqueraded as leg ulceration due to peripheral vascular disease in the absence of renal replacement therapy.
Topics: Aged; Amputation, Surgical; Arterial Occlusive Diseases; Calciphylaxis; Diagnosis, Differential; Female; Humans; Ischemia; Kidney Failure, Chronic; Leg; Leg Ulcer; Uremia
PubMed: 24878953
DOI: No ID Found -
Clinical Case Reports Jan 2021For small lesions, conservative management including local wound care, debridement, and adjustment of renal replacement therapy may suffice. Consulting palliative care...
For small lesions, conservative management including local wound care, debridement, and adjustment of renal replacement therapy may suffice. Consulting palliative care is encouraged to help establish goals of care among patient, family, and medical team.
PubMed: 33489221
DOI: 10.1002/ccr3.3478 -
Advances in Therapy Dec 2020Calciphylaxis is a deadly, painful disease with a 1-year mortality of up to 50%. The disease is commonly associated with patients with end-stage kidney disease (ESKD),... (Review)
Review
Calciphylaxis is a deadly, painful disease with a 1-year mortality of up to 50%. The disease is commonly associated with patients with end-stage kidney disease (ESKD), but it can manifest in non-uremic patients as well. In patients who are undergoing dialysis, the incidence of calciphylaxis can range from 0.04% to 4%. The progressive arterial calcification seen in calciphylaxis can affect multiple body organs, including the skin, brain, lungs, and muscle. In cutaneous calciphylaxis, painful and non-healing nodules, plaques, and ulcers may appear, increasing morbidity for patients. Diagnosis can be difficult, and the condition can clinically appear similar to other dermatological diseases, especially in non-uremic patients. Currently, skin biopsy with histological analysis is the most reliable method to help diagnose the condition. In certain cases, the use of medical imaging may be helpful. Treatment of pain in this condition can be difficult and should be multimodal and include wound care as well as modification of risk factors. Analgesic options include opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), as well as analgesic options that are targeted for specific patients. There are currently multiple clinical trials underway that are studying targeted therapies for this condition.
Topics: Calciphylaxis; Disease Management; Disease Progression; Humans; Kidney Failure, Chronic; Renal Dialysis; Risk Factors; Skin
PubMed: 32997277
DOI: 10.1007/s12325-020-01504-w -
JAMA Dermatology Mar 2017Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether... (Review)
Review
IMPORTANCE
Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis.
OBJECTIVE
To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.
DESIGN, SETTING, AND PARTICIPANTS
We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation).
EXPOSURES
Each patient had been exposed to warfarin before the onset of calciphylaxis.
MAIN OUTCOMES AND MEASURES
Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible.
RESULTS
We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death.
CONCLUSIONS AND RELEVANCE
Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.
Topics: Anticoagulants; Calciphylaxis; Female; Humans; Leg Ulcer; Livedo Reticularis; Purpura; Warfarin
PubMed: 28099971
DOI: 10.1001/jamadermatol.2016.4821