Sample records for calciphylaxis

  1. Calciphylaxis

    Directory of Open Access Journals (Sweden)

    Nicolás Raimondi


    Full Text Available Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles. It most frequently compromises patients with terminal chronic renal failure and has a high mortality rate. Biopsy of skin lesions is used as a diagnostic method. No specific laboratory findings have been recorded. Skin lesions usually begin in the extremities like a painful purplish mottling similar to "livedo reticularis". The natural evolution is to ulcers and bedsores. The first line of treatment involves the care of skin lesions and antibiotic therapy. Sodium thiosulfate is used as treatment due to its antioxidant activity and as a chelating. Two clinical cases are here reported

  2. Gastrointestinal Bleeding Secondary to Calciphylaxis (United States)

    Gupta, Nancy; Haq, Khwaja F.; Mahajan, Sugandhi; Nagpal, Prashant; Doshi, Bijal


    Patient: Female, 66 Final Diagnosis: Calciphylaxis Symptoms: Gastrointesinal haemorrhage Medication: None Clinical Procedure: Hemodialysis • blood transfusions Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Calciphylaxis is associated with a high mortality that approaches 80%. The diagnosis is usually made when obvious skin lesions (painful violaceous mottling of the skin) are present. However, visceral involvement is rare. We present a case of calciphylaxis leading to lower gastrointestinal (GI) bleeding and rectal ulceration of the GI mucosa. Case Report: A 66-year-old woman with past medical history of diabetes mellitus, hypertension, end-stage renal disease (ESRD), recently diagnosed ovarian cancer, and on hemodialysis (HD) presented with painful black necrotic eschar on both legs. The radiograph of the legs demonstrated extensive calcification of the lower extremity arteries. The hospital course was complicated with lower GI bleeding. A CT scan of the abdomen revealed severe circumferential calcification of the abdominal aorta, celiac artery, and superior and inferior mesenteric arteries and their branches. Colonoscopy revealed severe rectal necrosis. She was deemed to be a poor surgical candidate due to comorbidities and presence of extensive vascular calcifications. Recurrent episodes of profuse GI bleeding were managed conservatively with blood transfusion as needed. Following her diagnosis of calciphylaxis, supplementation with vitamin D and calcium containing phosphate binders was stopped. She was started on daily hemodialysis with low calcium dialysate bath as well as intravenous sodium thiosulphate. The clinical condition of the patient deteriorated. The patient died secondary to multiorgan failure. Conclusions: Calciphylaxis leading to intestinal ischemia/perforation should be considered in the differential diagnosis in ESRD on HD presenting with abdominal pain or GI bleeding. PMID:26572938

  3. Calciphylaxis following kidney transplantation: a case report

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    Hanvesakul Rajesh


    Full Text Available Abstract Introduction Calciphylaxis occurring after kidney transplantation is rare and rarely reported. It results in chronic non-healing wounds and is associated with a poor prognosis and is often fatal. We present a case of proximal lower limb calciphylaxis that occurred early after kidney transplantation. The patient had no classic associated risk factors. He had previously had a total parathyroidectomy but had normal serum calcium-phosphate product and parathyroid hormone levels. The clinical outcome of this case was favorable and highlights some fundamental issues relating to management. Case presentation A 70-year-old British Caucasian man with end-stage renal failure secondary to IgA nephropathy presented six months post kidney transplantation with cutaneous calciphylaxis lesions involving the medial aspect of the thigh bilaterally. Conclusion To the best of our knowledge, this is the first reported case of rapid onset cutaneous calciphylaxis occurring soon after kidney transplantation that was associated with a favorable outcome. Cutaneous calciphylaxis lesions should be promptly managed with meticulous wound care, antimicrobial therapy and the correction of calcium-phosphate product where indicated.

  4. Calciphylaxis: no longer rare; no longer calciphylaxis? A paradigm shift for wound, ostomy and continence nursing. (United States)

    Feeser, Dianne L


    This article challenges conventional wisdom that calciphylaxis is a rare condition. Rather, emerging evidence suggests that calciphylaxis is neither rare nor uncommon. In addition, the term calciphylaxis is questioned because misrepresents the underlying etiology of the condition. Multiple researchers and clinicians advocate abandoning the use of the term, but nursing literature has not yet followed suit. This article reviews the epidemiology, clinical manifestations, diagnosis, prevention, and treatment of this condition and associated wounds, and suggests areas for future research. The WOC nurse's role as an educator, leader, researcher, clinical expert, and patient advocate is summarized.

  5. Calciphylaxis after Parathyroidectomy in Chronic Renal Failure

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    Wahab Muhammad


    Full Text Available A 33-year-old man, who was maintained on hemodialysis for more than 9 years, was diagnosed to have secondary hyperparathyroidism with a nodule in a parathyroid gland revealed with ultrasound and CT scan. He underwent parathyroidectomy and presented with bilateral lower limb painful ulcers two months later. Skin biopsy from these ulcers was consistent with calciphylaxis.

  6. Calciphylaxis: Beyond CKD-MBD. (United States)

    Fernández, María; Morales, Enrique; Gutierrez, Eduardo; Polanco, Natalia; Hernández, Eduardo; Mérida, Eva; Praga, Manuel

    Calcific uraemic arteriolopathy (CUA), also called calciphylaxis, is a rare but potentially fatal vascular disorder that almost exclusively affects patients with chronic renal failure. The objective of this study was to analyse various risk factors for developing CUA and its subsequent clinical course according to the treatment received. A retrospective study that included patients diagnosed with CUA from December 1999 to December 2015. Various risk factors, clinical course and treatment options were analysed. A total of 28 patients (53.6% females) with a mean age of 67.2±11.8 (38-88) years were included. At the time of diagnosis, 53.6% were on haemodialysis, 25% were kidney transplant patients and 21.4% had normal renal function. The use of steroids (100%, P=.001) was the main risk factor in renal transplant patients. Skin lesions resolved in 60.7% (especially in those receiving multitargeted therapy). Patient survival at 12 months was 29% in transplant patients, 57% in haemodialysis patients and 100% in normal renal function patients (log-rank 6.88, P=.032). Chronic renal failure (P=.03) and hypoalbuminaemia (P=.02) were the main risk factor for CUA mortality. Although the incidence of CUA remains low, CUA mortality is very high, Special attention to its occurrence in kidney transplant patients and «non-renal» CUA forms is required. Oral anticoagulants and steroids appear to be the main risk factors, CUA is a challenge; a registry of patients and determining standard therapy are required. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Warfarin-induced calciphylaxis successfully treated with sodium thiosulphate. (United States)

    Hafiji, Juber; Deegan, Patrick; Brais, Rebecca; Norris, Paul


    Calciphylaxis is a rare life-threatening form of skin necrosis. Although traditionally observed in patients with end-stage renal disease and/or hyperparathyroidism, calciphylaxis has also been reported to occur in 'non-traditional' patients with normal renal and parathyroid function. We report a case of warfarin-induced calciphylaxis treated successfully with sodium thiosulphate and discuss the role of Vitamin K2 as a potential therapeutic option in the management of warfarin-induced calciphylaxis. © 2012 The Authors. Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.

  8. Systemic calciphylaxis presenting as a painful, proximal myopathy.


    Edelstein, C. L.; Wickham, M. K.; Kirby, P. A.


    A renal transplant patient who presented with a painful, proximal myopathy due to systemic calciphylaxis is described. The myopathy preceded the characteristic skin and soft tissue necrosis. Systemic calciphylaxis should be considered in a dialysis or a renal transplant patient presenting with a painful proximal myopathy even in the absence of necrotic skin lesions.

  9. Tumoral calcinosis, calciphylaxis, hyperparathyroidism and tuberculosis in a dialysis patient

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    Khawla Kammoun


    Full Text Available Tumoral calcinosis and calciphylaxis are uncommon but severe complications in ure-mic patients. They occur generally after long-term hemodialysis (HD treatment explained by ad-vanced secondary hyperparathyroidism and longstanding high calcium phosphorus product (Ca × P. Other factors such granulomatous diseases may worsen the calcium phosphate homeostasis alterations. We report a young male patient treated by HD for 6 years who developed tuberculosis in addition to tumoral calcinosis and calciphylaxis.

  10. Quantifying a rare disease in administrative data: the example of calciphylaxis. (United States)

    Nigwekar, Sagar U; Solid, Craig A; Ankers, Elizabeth; Malhotra, Rajeev; Eggert, William; Turchin, Alexander; Thadhani, Ravi I; Herzog, Charles A


    Calciphylaxis, a rare disease seen in chronic dialysis patients, is associated with significant morbidity and mortality. As is the case with other rare diseases, the precise epidemiology of calciphylaxis remains unknown. Absence of a unique International Classification of Diseases (ICD) code impedes its identification in large administrative databases such as the United States Renal Data System (USRDS) and hinders patient-oriented research. This study was designed to develop an algorithm to accurately identify cases of calciphylaxis and to examine its incidence and mortality. Along with many other diagnoses, calciphylaxis is included in ICD-9 code 275.49, Other Disorders of Calcium Metabolism. Since calciphylaxis is the only disorder listed under this code that requires a skin biopsy for diagnosis, we theorized that simultaneous application of code 275.49 and skin biopsy procedure codes would accurately identify calciphylaxis cases. This novel algorithm was developed using the Partners Research Patient Data Registry (RPDR) (n = 11,451 chronic hemodialysis patients over study period January 2002 to December 2011) using natural language processing and review of medical and pathology records (the gold-standard strategy). We then applied this algorithm to the USRDS to investigate calciphylaxis incidence and mortality. Comparison of our novel research strategy against the gold standard yielded: sensitivity 89.2%, specificity 99.9%, positive likelihood ratio 3,382.3, negative likelihood ratio 0.11, and area under the curve 0.96. Application of the algorithm to the USRDS identified 649 incident calciphylaxis cases over the study period. Although calciphylaxis is rare, its incidence has been increasing, with a major inflection point during 2006-2007, which corresponded with specific addition of calciphylaxis under code 275.49 in October 2006. Calciphylaxis incidence continued to rise even after limiting the study period to 2007 onwards (from 3.7 to 5.7 per 10

  11. [Incidence and characteristics of calciphylaxis in Martinique (2006-2012)]. (United States)

    Aoun, A; Baubion, E; Banydeen, R; Djiconkpode, I; Ekindi, N; Ureña-Torres, P; Riaux, A; Sadreux, T; Dueymes, J-M; Quist, D; Derancourt, C


    Calciphylaxis is a rare and severe disease with an annual incidence of around 1 % in dialysis patients. The main study aim was to determine its incidence in Martinique, where there is a significant population of patients on dialysis. All patients diagnosed with calciphylaxis between 2006 and 2012 and living in Martinique were included, retrospectively. Social, demographic, biological, anatomic, pathological, histological and outcome data were analysed. Fifteen patients were included (8 women, 7 men). The incidence of calciphylaxis in this population was about 4.62/1,000,000 inhabitants per year. All patients presented very painful skin ulcerations and necrosis, chiefly on the lower extremities in 53.3 % of cases. All patients were on haemodialysis and two had undergone renal transplantation. Fourteen of the 15 patients were presenting secondary hyperparathyroidism, 12 had hypertension, 9 peripheral arterial disease, 8 obesity and 8 diabetes mellitus. Raised calcium and phosphorus were noted in 8 patients, with hypoalbuminaemia in 9 patients. Treatment with sodium thiosulfate was given for 8 patients, and was beneficial for all after a mean duration of 3.4 months. After 6 months of follow-up, 8 of the 15 patients were cured, 1 showed improvement and 6 had died. To our knowledge, this is the first study to examine the incidence of calciphylaxis in the general population. The relatively large number of patients could be accounted for by the high number of comorbidities in end-stage renal disease patients in Martinique, including obesity, diabetes, hypertension and arteritis. Treatment with sodium thiosulfate was beneficial for 8 patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Calciphylaxis - A case study in a patient with Maori heritage. (United States)

    Kingi, Lawrence; Grech, Roger; Lam, Michael; Dissanayake, Ajith; Otter, Simon


    This case history describes a rare complaint - Calciphylaxis, seen in a New Zealand Maori patient undergoing renal dialysis. This condition causes non-healing tissue ulceration, typically with sepsis and is associated with a very high mortality rate. The need for vigilance among health professionals is highlighted, including the risk factors that may faciliate an early diagnosis; together with the value associated with a multi-disciplinary team approach to management. Copyright © 2016 Tissue Viability Society. All rights reserved.

  13. Calciphylaxis: Temporal Artery Calcification Preceding Widespread Skin Lesions and Penile Necrosis

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    Manzoor A. Shah


    Full Text Available Temporal artery calciphylaxis has rarely been described in chronic kidney disease patients on dialysis. We report a case of 72-year-old Caucasian man with multiple comorbidities and end-stage renal disease on dialysis who presented with temporal artery calcification leading to bilateral loss of vision followed by extensive skin lesions including one on glans penis. While on peritoneal dialysis, he developed anterior ischemic optic neuropathy, had no improvement on high dose steroids, and temporal artery biopsy showed marked calcification without any evidence of vasculitis. Few weeks later on hemodialysis, he developed widespread cutaneous lesions on extremities and penile necrosis with skin biopsy revealing calciphylaxis. On literature review of calciphylaxis in chronic kidney disease, we found only four cases of temporal artery calciphylaxis leading to anterior ischemic optic neuropathy and blindness. We believe this is the first case in which the rare temporal artery calciphylaxis and the uncommon penile necrosis are being described together. The objective is to emphasize the need to recognize this condition early in the CKD patients on dialysis presenting with visual symptoms as the different treatment strategies may help prevent complete loss of vision and also modify or prevent a full blown calciphylaxis.

  14. Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis

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    Jee Eun Park


    Full Text Available Warfarin skin necrosis (WSN is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.

  15. Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis. (United States)

    Nigwekar, Sagar U; Bloch, Donald B; Nazarian, Rosalynn M; Vermeer, Cees; Booth, Sarah L; Xu, Dihua; Thadhani, Ravi I; Malhotra, Rajeev


    Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; P =0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses ( β =-8.99; P =0.04). In conclusion, vitamin K deficiency-mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study. Copyright © 2017 by the American Society of Nephrology.

  16. Serum calcium and phosphorus concentrations and the outcome of calciphylaxis treatment with sodium thiosulfate

    Czech Academy of Sciences Publication Activity Database

    Hlušička, J.; Veisová, E.; Ullrych, M.; Kubeček, J.; Navrátil, Tomáš; Zakharov, S.


    Roč. 148, č. 3 (2017), s. 435-440 ISSN 0026-9247 Institutional support: RVO:61388955 Keywords : Calciphylaxis * Sodium thiosulfate * Serum calcium Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 1.282, year: 2016

  17. Calciphylaxis and Martorell Hypertensive Ischemic Leg Ulcer: Same Pattern - One Pathophysiology. (United States)

    Hafner, Jürg


    This review presents a closer look at four diseases which are probably closely related to one another pathophysiologically: (a) calciphylaxis (distal pattern); (b) calciphylaxis (proximal pattern); (c) Martorell hypertensive ischemic leg ulcer; (d) calciphylaxis with normal renal and parathyroid function (synonym: eutrophication). The four diseases have largely the same risk factors: (1) arterial hypertension, (2) diabetes mellitus (types 1 and 2), (3) secondary or tertiary hyperparathyroidism (in end-stage kidney disease) and (4) oral anticoagulation with vitamin K antagonists. They share the same clinical patterns: necrotizing livedo, skin infarctions at typical locations and acral gangrene in calciphylaxis. They also share the same histopathology: ischemic subcutaneous arteriolosclerosis and small-artery disease and 'miniaturizing' Mönckeberg medial calcinosis. The treatment concept for the acute phase of the diseases is also broadly similar. In addition to an optimized control of the cardiovascular risk factors, a proactive wound approach (necrosectomy, negative pressure wound treatment with vacuum dressings, and early skin grafts supported by systemic antibiotic therapy) leads most rapidly and effectively to a reduction of the initially severe wound pain, and finally to complete healing of the wound. Oral anticoagulation with vitamin K antagonists should be stopped. In extensive cases, the use of intravenous sodium thiosulfate is recommended. All four diagnoses are little known in the medical schools of most countries. The need to improve familiarity with these four closely related disorders is therefore great. In particular, the risk of confusion with pyoderma gangrenosum is a major diagnostic problem which can lead to false and even damaging treatment. © 2016 S. Karger AG, Basel.

  18. Calciphylaxis – a challenging & solvable task for plastic surgery? A case report

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    Tsolakidis Savas


    Full Text Available Abstract Background Calciphylaxis (calcific uremic arteriolopathy is rare and its pathogenesis is not fully understood. Indeed, Calciphylaxis presents a challenge through the course of its management which involve different specialities but unfortunately this disease so far has a poor prognosis. We herein present, in this case report, a multidisciplinary approach involving plastic surgeons with special regards to reconstructive approach after debridement procedures. Case presentation We present a 21 years old male with a BMI of 38,2, who was transferred to our department from another hospital. Calciphylaxis has been diagnosed after receiving anticoagulation with phenprocoumon after a single event of pulmonary embolism. The INR on admission was 1,79. He had necrotic spots on both sides of the abdominal wall and on both thighs medially. During this time he underwent several reconstructive procedures in our department. Conclusion It can be suggested that this agonizing disease needs indeed a multidisciplinary approach involving Nephrologists, Dermatologists, Intensive Care Physicians and Plastic Surgeons, taking into consideration that surgical correction can achieve further improvement in a specialized centre. Notwithstanding, further cohort studies should be approached clinically to insight the light on this disease with special regard to the prognosis after this approach.

  19. Calciphylaxis: a devastating complication of derangements of calcium-phosphorus metabolism--a case report and review of the literature. (United States)

    Carter, Trish; Ratnam, Shobha


    Calciphylaxis is a rare and potentially devastating condition also referred to as uremic gangrene syndrome, calcific uremic arteriolopathy, metastatic calcification, and uremic small-vessel disease that can present in patients with end stage renal disease. This article reports a case of a 38-year-old African-American female on peritoneal dialysis for six years with a known history of non-adherence with diet, medications, and prescribed peritoneal dialysis treatment regimen. At her monthly clinic visit, the patient complained of burning sensation in the fingers of both hands with limited fine motor movement due to edema and severe pain. A presumptive diagnosis of calciphylaxis led to hospital admission with confirmation by X-ray of her hands. The patient was switched to hemodialysis with low calcium dialysate, aggressive reduction in phosphorus, diet counseling, use of cinacalcet, and six weeks of intravenous sodium thiosulfate infusion with hemodialysis treatments. The patient's condition improved with resolution of symptoms. This case was chosen based on the rarity of a calciphylaxis presentation and paucity of knowledge regarding diagnosis and treatment.

  20. Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1-34)] therapy in the setting of chronic warfarin and glucocorticoid treatment. (United States)

    Spanakis, E K; Sellmeyer, D E


    Calciphylaxis occurs rarely in the absence of end stage renal disease. Predisposing factors for nonuremic calciphylaxis (NUC) include hyperparathyroidism, coagulopathies, connective tissue disease, liver disease, glucocorticoid use, and malignancy. Warfarin can facilitate vascular calcification by reducing vitamin K-dependent carboxylation of matrix-Gla proteins. An 86-year-old Caucasian woman with a history of polymyalgia rheumatica, two spontaneous deep venous thromboses (DVTs) and multiple fractures was treated with calcium, vitamin D, prednisone, and warfarin. The patient's low bone density was treated initially with estrogen, then oral bisphosphonate, which was discontinued due to upper gastrointestinal symptoms. Nasal calcitonin was initiated. After 10 years of calcitonin treatment, she was changed to teriparatide. Two months after initiating teriparatide, she developed lower extremity edema and painful erythematous nodular lesions on her calves bilaterally, that progressed to necrotic ulcers despite antibiotic therapy. Biopsy of the lesions showed calcification in the media of small blood vessels and subcutaneous fat with fat necrosis, consistent with calciphylaxis. Teriparatide was discontinued. Aggressive wound care, antibiotics, and intravenous zoledronic acid were initiated. With cessation of teriparatide therapy and intensive wound care, the patient's lesions resolved over 8 months. We report the first case of NUC precipitated by teriparatide therapy. Our patient had multiple underlying predisposing factors including a connective tissue disorder, glucocorticoid therapy, warfarin use, and possible underlying coagulopathy given her history of multiple DVTs. In such patients, alternative osteoporosis therapies may be preferred.

  1. Integrated image data and medical record management for rare disease registries. A general framework and its instantiation to theGerman Calciphylaxis Registry. (United States)

    Deserno, Thomas M; Haak, Daniel; Brandenburg, Vincent; Deserno, Verena; Classen, Christoph; Specht, Paula


    Especially for investigator-initiated research at universities and academic institutions, Internet-based rare disease registries (RDR) are required that integrate electronic data capture (EDC) with automatic image analysis or manual image annotation. We propose a modular framework merging alpha-numerical and binary data capture. In concordance with the Office of Rare Diseases Research recommendations, a requirement analysis was performed based on several RDR databases currently hosted at Uniklinik RWTH Aachen, Germany. With respect to the study management tool that is already successfully operating at the Clinical Trial Center Aachen, the Google Web Toolkit was chosen with Hibernate and Gilead connecting a MySQL database management system. Image and signal data integration and processing is supported by Apache Commons FileUpload-Library and ImageJ-based Java code, respectively. As a proof of concept, the framework is instantiated to the German Calciphylaxis Registry. The framework is composed of five mandatory core modules: (1) Data Core, (2) EDC, (3) Access Control, (4) Audit Trail, and (5) Terminology as well as six optional modules: (6) Binary Large Object (BLOB), (7) BLOB Analysis, (8) Standard Operation Procedure, (9) Communication, (10) Pseudonymization, and (11) Biorepository. Modules 1-7 are implemented in the German Calciphylaxis Registry. The proposed RDR framework is easily instantiated and directly integrates image management and analysis. As open source software, it may assist improved data collection and analysis of rare diseases in near future.

  2. Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

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    Sowers James R


    Full Text Available Abstract Background Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling. The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall. Results The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician – researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisioning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. Conclusion A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications.


    Directory of Open Access Journals (Sweden)

    Lourdes Bolla de Lezcano


    Full Text Available Resumen La calcifilaxis es un síndrome clínico caracterizado por una calcificación vascular progresiva que ocasiona la aparición de lesiones violáceas, frecuentemente dolorosas, en la piel de pacientes con insuficiencia renal crónica, diálisis o trasplante renal, asociado usualmente a niveles elevados de hormona paratiroidea. Se presenta el caso clínico de una mujer de 44 años, diabética con insuficiencia renal crónica, en hemodiálisis desde hace 2 años, que fue diagnosticada de calcifilaxis tras sospecha clínica y biopsia de lesiones cutáneas. Abstract Calciphylaxis is a clinical syndrome characterized by progressive vascular calcification that causes the appearance of purplish lesions, often painful, in the skin of patients with chronic renal failure, dialysis or kidney transplantation, usually associated with elevated levels of parathyroid hormone. We report a case of a 44-year-old diabetic woman with chronic renal failure on hemodialysis for 2 years. She was diagnosed with calciphylaxis after clinical suspicion and biopsy of skin lesions.

  4. Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal ...

    African Journals Online (AJOL)

    S Afr Med J 2017;107(2):140-144. DOI:10.7196/SAMJ.2017.v107i2.11058 ..... SLE = systemic lupus erythematosus; MHT = malignant hypertension; Reflux = reflux nephropathy; ... and there are no randomised trials available to guide therapy.

  5. Case Report: Calciphylaxis Causing Digital, Gangrene in End Stage ...

    African Journals Online (AJOL)

    It is more frequently reported in whites than in blacks and commonly accompanies hyperphosphataemia, elevated calcium-phosphate product and marked secondary hyperparathyroidism. We report a rare case of CUA that complicated end stage renal disease secondary to obstructive uropathy in a 68 year old Nigerian.

  6. Penile gangrene in diabetes mellitus with renal failure: A poor prognostic sign of systemic vascular calciphylaxis

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    Mayank Mohan Agarwal


    Full Text Available Penile gangrene associated with chronic renal failure is very uncommon. A 52-year-old man with diabetes mellitus, diffuse atherosclerosis, ischemic cardiomyopathy and end-stage renal disease presented with blackening of distal penis for 10 days. His general condition was poor and gangrene of prepuce and glans was noted. Doppler and magnetic-resonance angiography revealed bilateral internal iliac artery obstruction. He underwent trocar suprapubic cystostomy and was planned for partial penectomy. But he died of severe diabetic complications in the interim period. Penile gangrene is a manifestation of widespread vascular calcifications associated with end-stage renal disease and is a marker of poor prognosis.

  7. Case Series

    African Journals Online (AJOL)

    calciphylaxis is prevention through rigorous control of phosphate and calcium balance. We here present two ... The authors declared no conflict of interest. Introduction. Calciphylaxis is a rare but serious disorder .... were reported to resolve the calciphylaxis lesions in a chronic renal failure patient [20]. In a series of five.

  8. Predialytic treatment of chronic kidney disease

    African Journals Online (AJOL)


    Aug 16, 2007 ... in high turnover bone disease. Note the poor outline of the femurs. Fig. 4. Severe calciphylaxis in a patient with CKD. Note the extensive skin and subcutaneous infarc- tion with underlying muscle clearly visible. Predialytic treatment of CKD. 392. CME August 2007 Vol.25 No.8 pg389-394.indd 392. 8/16/07 ...

  9. 1-1-3

    African Journals Online (AJOL)

    tertiary hyperparathyroidism with severe metabolic bone disease. Five patients presented with rapidly progressing calciphylaxis. Three patients had grossly elevated serum calcium levels (l was comatose and 1 was confused) and an emergency parathyroidectomy was performed in these patients. Other symptoms were ...

  10. Penil kalcifylaksi

    DEFF Research Database (Denmark)

    Kjaerskov, Mette Wanscher; Comstedt, Lisbeth Rosholm; Bygum, Anette


    A 64-year-old diabetic man on peritoneal dialysis developed painful necrotic ulcers of the glans penis over a period of six months. On suspicion of atherosclerotic necrosis, a partial resection of his penis was performed. Histological examination showed calciphylaxis. This vasculopathy...... with calcification and intimal fibrosis in small blood vessels is mostly seen in patients with end-stage renal disease. The condition is characterized by painful livedoid and infiltrated plaques and ulcers. Involvement of the penis is rare, but probably underdiagnosed. Udgivelsesdato: 2009-May-25...

  11. Skin manifestations of chronic kidney disease. (United States)

    Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J


    Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  12. Necrotizing fasciitis due to Serratia marcescens: case report and review of the literature. (United States)

    Majumdar, Rohit; Crum-Cianflone, Nancy F


    Necrotizing fasciitis is a severe, life-threatening infection.  Serratia marcescens, a Gram-negative bacterium, is an extremely rare cause of necrotizing fasciitis. A case of S. marcescens necrotizing fasciitis is described, and a comprehensive review of the literature (1966-2015) of monomicrobial cases due to this organism performed. We report the first case of S. marcescens necrotizing fasciitis in the setting of calciphylaxis associated with end-stage renal disease.  A comprehensive review of the literature of S. marcescens necrotizing fasciitis is provided to enhance the awareness of this increasingly recognized infection, and to provide a concise summary of risk factors, treatment, and outcome. Our case and review highlight the potential risk factors for S. marcescens necrotizing fasciitis, including underlying renal disease and open wounds, and demonstrate the emergence of this organism as a cause of severe, life-threatening soft tissue infections.

  13. The strength of a calcified tissue depends in part on the molecular structure and organization of its constituent mineral crystals in their organic matrix (United States)

    Landis, W. J.


    High-voltage electron-microscopic tomographic (3D) studies of the ultrastructural interaction between mineral and organic matrix in a variety of calcified tissues reveal different crystal structural and organizational features in association with their respective organic matrices. In brittle or weak pathologic or ectopic calcifications, including examples of osteogenesis imperfecta, calciphylaxis, calcergy, and dermatomyositis, hydroxyapatite crystals occur in various sizes and shapes and are oriented and aligned with respect to collagen in a manner which is distinct from that found in normal calcified tissues. A model of collagen-mineral interaction is proposed which may account for the observed crystal structures and organization. The results indicate that the ultimate strength, support, and other mechanical properties provided by a calcified tissue are dependent in part upon the molecular structure and arrangement of its constituent mineral crystals within their organic matrix.

  14. Adipocyte induced arterial calcification is prevented with sodium thiosulfate

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    Chen, Neal X., E-mail: [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); O’Neill, Kalisha; Akl, Nader Kassis [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); Moe, Sharon M. [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); Roudebush VA Medical Center, Indianapolis, IN (United States)


    Highlights: • High phosphorus can induce calcification of adipocytes, even when fully differentiated. • Adipocytes can induce vascular calcification in an autocrine manner. • Sodium thiosulfate inhibits adipocyte calcification. - Abstract: Background: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. Methods: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. Results: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. Conclusion: High phosphorus induced calcification of mature adipocytes, and

  15. Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient

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    Lilia Ben Fatma


    Full Text Available Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcu-taneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadro-parin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calci-phylaxis, outcome is favorable.

  16. ¿Qué hay de nuevo en calcifilaxia?

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    Juan Carlos Restrepo Medrano


    Full Text Available Objective: To analyze the scientifi c literature published in the main databases between 1962 and 2016, whose objective was to address the issue of calciphylaxis and its main characteristics? Methodology: A literature review was carried out in the main databases of the Health Sciences and Social Sciences (medline-pubmed, cinhal, web of science, lilacs, sociological abstracts, cuiden, embase, psycoinfo and isi web of knowledge. An analytical review of the selected articles was made using a protocol to extract the data. Results: 45 articles were found that fulfi lled the established search criteria, 35 reported the results of clinical trials or qualitative studies, 4 corresponded to systematic reviews and 6 were classifi ed as retrospective studies. The authors pointed out the main characteristics of the disease, the patients and the most used treatments, but little of the care that should be provided by the nurse practitioner. Conclusion: In the analyzed studies, aspects regarding the course of the disease and treatment were identifi ed; it was reported the effectiveness of some treatments used in the care of these patients, but none of them defi nitive, which allows to propose some actions from the nurse discipline.

  17. OC ToGo: bed site image integration into OpenClinica with mobile devices (United States)

    Haak, Daniel; Gehlen, Johan; Jonas, Stephan; Deserno, Thomas M.


    Imaging and image-based measurements nowadays play an essential role in controlled clinical trials, but electronic data capture (EDC) systems insufficiently support integration of captured images by mobile devices (e.g. smartphones and tablets). The web application OpenClinica has established as one of the world's leading EDC systems and is used to collect, manage and store data of clinical trials in electronic case report forms (eCRFs). In this paper, we present a mobile application for instantaneous integration of images into OpenClinica directly during examination on patient's bed site. The communication between the Android application and OpenClinica is based on the simple object access protocol (SOAP) and representational state transfer (REST) web services for metadata, and secure file transfer protocol (SFTP) for image transfer, respectively. OpenClinica's web services are used to query context information (e.g. existing studies, events and subjects) and to import data into the eCRF, as well as export of eCRF metadata and structural information. A stable image transfer is ensured and progress information (e.g. remaining time) visualized to the user. The workflow is demonstrated for a European multi-center registry, where patients with calciphylaxis disease are included. Our approach improves the EDC workflow, saves time, and reduces costs. Furthermore, data privacy is enhanced, since storage of private health data on the imaging devices becomes obsolete.

  18. [Skin and chronic kidney disease]. (United States)

    Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio


    Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process.

  19. Penile calcific uremic arteriolopathy occurring postparathyroidectomy in a hemodialysis patient

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    Salah Omar Bashir


    Full Text Available Calcific uremic arteriolopathy (CUA, also known as calciphylaxis, is a rare condition most frequently seen in patients with advanced chronic kidney disease. The clinical picture is characterized by painful skin lesions and ulcerations. The underlying pathology is medial calcification and intimal proliferation with microthrombi of small arteries. CUA is commonly associated with secondary hyperparathyroidism and high serum calcium and phosphate products. This article reports an atypical case where CUA developed after parathyroidectomy and in the course of treatment of hungry bone syndrome. The patient was on hemodialysis for 14 years. He had developed secondary hyperparathyroidism and severe osteodystrophy. Calcium, Vitamin-D supplements, and calcimimetics failed to control his condition. He underwent parathyroidectomy but developed hungry bone syndrome postoperatively. He was managed with large doses of calcium and active Vitamin-D analogs to maintain his serum calcium. Two weeks later, he developed a painful single lesion on the tip of the penis which was diagnosed as CUA on clinical and radiographic evidence. The patient refused surgical intervention and opted for traditional treatment with honey and herbs with an excellent outcome. The case highlights the risk of CUA complicating the aggressive management of post-parathyroidectomy hungry bone syndrome.

  20. Calcific Uremic Arteriolopathy: Pathophysiology, Reactive Oxygen Species and Therapeutic Approaches

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    Kurt M. Sowers


    Full Text Available Calcific uremic arteriolopathy (CUA/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.

  1. Wound Healing in Patients With Impaired Kidney Function. (United States)

    Maroz, Natallia; Simman, Richard


    Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium-phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients.

  2. Beyond the futility argument: the fair process approach and time-limited trials for managing dialysis conflict. (United States)

    Rinehart, Ann


    Futility is an ancient concept arising from Greek mythology that was resurrected for its medical application in the 1980s with the proliferation of many lifesaving technologies, including dialysis and renal transplantation. By that time, the domineering medical paternalism that characterized the pre-1960s physician-patient relationship morphed into assertive patient autonomy, and some patients began to claim the right to demand aggressive, high-technology interventions, despite physician disapproval. To counter this power struggle, the establishment of a precise definition of futility offered hope for a futility policy that would allow physicians to justify withholding or withdrawing treatment, despite patient and family objections. This article reviews the various attempts made to define medical futility and describes their limited applicability to dialysis. When futility concerns arise, physicians should recognize the opportunity to address conflict, using best practice communication skills. Physicians would also benefit from understanding the ethical principles of respect for patient autonomy, beneficence, nonmaleficence, justice, and professional integrity that underlie medical decision-making. Also reviewed is the use of a fair process approach or time-limited trial when conflict resolution cannot be achieved. These topics are addressed in the Renal Physician Association's clinical practice guideline Shared Decision-Making in the Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists should be well versed. A case presentation of intractable calciphylaxis in a new dialysis patient illustrates the pitfalls of physicians not fully appreciating the ethics of medical decision-making and failing to use effective conflict management approaches in the clinical practice guideline.

  3. Human wound photogrammetry with low-cost hardware based on automatic calibration of geometry and color (United States)

    Jose, Abin; Haak, Daniel; Jonas, Stephan; Brandenburg, Vincent; Deserno, Thomas M.


    Photographic documentation and image-based wound assessment is frequently performed in medical diagnostics, patient care, and clinical research. To support quantitative assessment, photographic imaging is based on expensive and high-quality hardware and still needs appropriate registration and calibration. Using inexpensive consumer hardware such as smartphone-integrated cameras, calibration of geometry, color, and contrast is challenging. Some methods involve color calibration using a reference pattern such as a standard color card, which is located manually in the photographs. In this paper, we adopt the lattice detection algorithm by Park et al. from real world to medicine. At first, the algorithm extracts and clusters feature points according to their local intensity patterns. Groups of similar points are fed into a selection process, which tests for suitability as a lattice grid. The group which describes the largest probability of the meshes of a lattice is selected and from it a template for an initial lattice cell is extracted. Then, a Markov random field is modeled. Using the mean-shift belief propagation, the detection of the 2D lattice is solved iteratively as a spatial tracking problem. Least-squares geometric calibration of projective distortions and non-linear color calibration in RGB space is supported by 35 corner points of 24 color patches, respectively. The method is tested on 37 photographs taken from the German Calciphylaxis registry, where non-standardized photographic documentation is collected nationwide from all contributing trial sites. In all images, the reference card location is correctly identified. At least, 28 out of 35 lattice points were detected, outperforming the SIFT-based approach previously applied. Based on these coordinates, robust geometry and color registration is performed making the photographs comparable for quantitative analysis.

  4. Beyond the Futility Argument: The Fair Process Approach and Time-Limited Trials for Managing Dialysis Conflict (United States)


    Summary Futility is an ancient concept arising from Greek mythology that was resurrected for its medical application in the 1980s with the proliferation of many lifesaving technologies, including dialysis and renal transplantation. By that time, the domineering medical paternalism that characterized the pre-1960s physician–patient relationship morphed into assertive patient autonomy, and some patients began to claim the right to demand aggressive, high-technology interventions, despite physician disapproval. To counter this power struggle, the establishment of a precise definition of futility offered hope for a futility policy that would allow physicians to justify withholding or withdrawing treatment, despite patient and family objections. This article reviews the various attempts made to define medical futility and describes their limited applicability to dialysis. When futility concerns arise, physicians should recognize the opportunity to address conflict, using best practice communication skills. Physicians would also benefit from understanding the ethical principles of respect for patient autonomy, beneficence, nonmaleficence, justice, and professional integrity that underlie medical decision-making. Also reviewed is the use of a fair process approach or time-limited trial when conflict resolution cannot be achieved. These topics are addressed in the Renal Physician Association’s clinical practice guideline Shared Decision-Making in the Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists should be well versed. A case presentation of intractable calciphylaxis in a new dialysis patient illustrates the pitfalls of physicians not fully appreciating the ethics of medical decision-making and failing to use effective conflict management approaches in the clinical practice guideline. PMID:23868900