Magro, Cynthia M; Simman, Richard; Jackson, Sarah
Human calciphylaxis reflects a form of severe tissue compromise attributable to a unique microangiopathy that combines features of vascular thrombotic occlusion with endoluminal calcification. While most frequently described in patients with renal failure, it is seen in other settings, such as multiple myeloma; polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome; cirrhosis; and rheumatoid arthritis. Although most commonly involving the skin, calciphylaxi...
Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical...
Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently new medical treatments emerged aiming to normalize disturbances of minerals to reduce the serum concentration of sodium phosphate and to prevent precipitation and calcification. Multimodal therapy is warranted but only aggressive surgical debridement of cutaneous ulcers has shown significant outcome improvement. PMID:23716795
Full Text Available Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently new medical treatments emerged aiming to normalize disturbances of minerals to reduce the serum concentration of sodium phosphate and to prevent precipitation and calcification. Multimodal therapy is warranted but only aggressive surgical debridement of cutaneous ulcers has shown significant outcome improvement.
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. PMID:23581997
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.
Zhang, Yanchen; Corapi, Kristin M; Luongo, Maria; Thadhani, Ravi; Nigwekar, Sagar U
Background Calciphylaxis is a rare but devastating condition in end-stage renal disease (ESRD) patients. Most research in the field of calciphylaxis is focused on hemodialysis (HD) patients; however, data on calciphylaxis incidence, risk factors, and mortality in peritoneal dialysis (PD) patients are limited. Methods In this cohort study, we examined data from adult patients who initiated PD for ESRD management at our institute’s PD unit from January 2001 to December 2015. Associations with the development of calciphylaxis were examined for clinical, laboratory, and medication exposures. Incidence of calciphylaxis and mortality in PD patients who developed calciphylaxis were analyzed. Treatments administered to treat calciphylaxis in PD patients were summarized. Results In this cohort of 63 patients, 7 patients developed calciphylaxis (incidence rate: 9.0 per 1,000 patient-years). Median age of PD patients who developed calciphylaxis was 50 years, 57% were white, 71% females, and 71% were previously on HD. Female sex, obesity, HD as a prior dialysis modality, recurrent hypotension, elevated time-averaged serum phosphorous levels, reduced time-averaged serum albumin levels, and warfarin therapy were associated with increased calciphylaxis risk in univariate logistic regression analyses. Intravenous sodium thiosulfate was administered in 57% of PD patients who developed calciphylaxis. One-year mortality in PD patients who developed calciphylaxis was 71% despite multimodal treatment including sodium thiosulfate, hyperbaric oxygen, cinacalcet, and wound debridement. Conclusion Calciphylaxis is a rare but frequently fatal condition in PD patients. Our study provides critical early insights into calciphylaxis incidence, risk factors, and prognosis in PD patients. Sample size and characteristics of patients included in our study limit generalizability to overall PD population and warrant examination in larger independent studies. PMID:27698566
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.
Maroz, Natallia; Mohandes, Samer; Field, Halle; Kabakov, Zlata; Simman, Richard
Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a devastating disease typically seen in patients with end stage renal disease. It manifests as extremely painful symmetrical wounds resistant to surgical and medical interventions. The prevalence of CUA among hemodialysis dependent patients was found to be as high as 4.1%. The management of patients with CUA requires a multidisciplinary approach by the medical team, yet often results in a low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has been described in the absence of kidney disease. Limited knowledge exists on the management of NUC and the outcomes of this condition. Herein we describe three clinical scenarios of patients diagnosed with NUC in the absence of permanent or prolonged acute renal pathology. The reporting of successful and fruitless therapeutic interventions for wound management in NUC is important for compiling the evidence of effective therapeutic strategies.
Full Text Available Although soft tissue and vascular calcifications are common in CKD and progress as an independent risk factor of all-cause mortality, tumour calcification and calciphylaxis are uncommon in patients with end-stage renal disease (ESRD. Here, we discuss a rare case of a patient with tumour calcification complicated with calciphylaxis developed septic shock from infection. Our patient is a 57-year-old man in his late stage of renal disease who presented with a huge mass at the right hip and necrotic cutaneous ulcers on the lower legs followed by local and systemic infection and death due to septic shock.
Hammadah, Muhammad; Chaturvedi, Shruti; Jue, Jennifer; Buletko, Andrew Blake; Qintar, Mohammed; Madmani, Mohammed Eid; Sharma, Prashant
We are describing a case of 55-year-old obese female with significant history of uncontrolled rheumatoid arthritis, who recently had decreased her immune-suppression medications. She presented with extensive acral gangrene involving multiple fingers and toes. Clinical picture and laboratory findings were suggestive of vasculitis; however, skin biopsy established diagnosis of calciphylaxis, in settings of normal kidney function. Patient was treated with sodium thiosulfate with gradual improvem...
Full Text Available Abstract Background Calciphylaxis cutis is characterized by media calcification of arteries and, most prominently, of cutaneous and subcutaneous arterioles occurring in renal insufficiency patients. Case Report A 53-year-old woman with chronic cardiac and renal failure complained of painful crural, non-varicosis ulcers. She was hospitalized in an immobilized condition due to both the crural ulcerations and the existing heart-failure state (NYHA III-IV having pleural and pericardial effusions, atrial fibrillation and weight loss of 30 kg over the past year. Despite normalization of calcium-phosphorus balance and improvement of renal function, the clinical course of crural ulcerations deteriorated during the following 3 months. After failure of surgical debridements, multiple courses of sterile-maggot therapy were introduced at a late stage to stabilize the wounds. The patient died of recurrent wound infections and sepsis paralleled by exacerbations of renal malfunction. Conclusions The role of renal disease in vascular complications is discussed. Sterile-maggot debridement may constitute a therapy for the ulcerated calciphylaxis at an earlier stage, i.e. when first ulcerations appear.
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.
Full Text Available Calciphylaxis, or calcific uremic arteriolopathy, commonly affects people with end-stage renal disease and carries with it a high rate of morbidity and mortality. Here, we present the unusual case of a 56-year-old woman, with extensive medical problems, who developed calciphylaxis in the presence of primary hyperparathyroidism. Our patient initially presented with bilateral, exquisitely tender thigh lesions. The diagnosis of calciphylaxis was rendered histologically by extensive calcification of the subcutaneous blood vessels. Subsequent parathyroidectomy identified the presence of a hyperactive mediastinal parathyroid adenoma, weighing 0.62 grams. Postoperatively, the patient had normalization of hypercalcemia and parathyroid hormone levels, with subsequent healing of her thigh wounds. Currently, there have been sixteen cases described in the English literature, with only nine being offered a potentially therapeutic parathyroidectomy. It is contingent upon the vigilant physician to diagnose and properly manage this difficult yet treatable condition.
Park, Jee Eun; Byeon, Seonggyu; Kim, Hee Kyung; Moon, Seong Mi; Moon, Ji Hoon; Jang, Kee-Taek; Lee, Byung-Jae; Jang, Hye Ryoun; Huh, Wooseong; Kim, Dae Joong; Kim, Yoon-Goo; Oh, Ha Young; Lee, Jung Eun
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. PMID:27069859
Sandhu, Gagangeet; Gini, Marcelo Barrios; Ranade, Aditi; Djebali, David; Smith, Steven
Calciphylaxis or calcific uremic arteriolopathy is a life-threatening condition that predominantly affects patients with end-stage renal disease on hemodialysis. A prevalence of up to 4% and a 6-month mortality rate of up to 80% have been reported in those with proximal disease (thighs, abdomen wall, and buttocks). Penile calciphylaxis is very rare but has a mortality rate of 69% within 6 months. Its treatment is controversial. For small lesions, conservative treatment with local wound care and debridement may suffice. Partial or complete penectomy may be needed for more extensive lesions, and especially those associated with signs of local infection. In addition to surgical intervention, as with any other case of calcific uremic arteriolopathy, the cornerstones of therapy should be to keep serum phosphorus sodium thiosulfate was used in addition to the standard medical and surgical therapy. Two months after surgery, the patient's wound completely healed and he has experienced no new lesions over the past 11 months.
Full Text Available Ramón Alberto Tamayo-Isla, Mauro Cuba de la Cruz Internal Medicine Department, Pietersburg Provincial Hospital, Polokwane Kidney and Dialysis Centre, Limpopo Province, South Africa Introduction: Calciphylaxis is a rare medical condition that is usually diagnosed in patients suffering from end-stage renal disease who are already receiving renal replacement therapy and in those post-transplantation. The pathogenesis still remains to be fully elucidated; hence, the treatment is not uniform. The prognosis is generally poor. The ulcerative stage exhibits a worse prognosis than the nonulcerative one. Calciphylaxis presenting in terminal kidney disease prior to dialytic treatment has only rarely been reported. Case presentation: A 32-year-old female Caucasian clerk sought medical attention for increasing tiredness and lower limb skin ulcers. Polycystic kidney disease was diagnosed in her late father and two of her siblings. At the first nephrology consultation, obesity, pallor, bilateral flank masses with ballottement, and two ulcers with a dark necrotic center on the distal left leg were noted. In addition, another indurated light bluish lesion of 5 cm just above the right knee with intact skin was observed. All lesions were very tender and warm on touch. Laboratory results yielded hypercalcemia, hyperphosphatemia, anemia, and parathyroid hormone levels that were more than ten times the normal values in the patient, and with a glomerular filtration rate of 4 mL/minute. Skin biopsy confirmed the suspicion of calciphylaxis. The patient was placed on peritoneal dialysis with low Ca concentration baths, cinacalcet, and aluminum hydroxide. The results included correction of hypercalcemia, improvement of phosphate levels, and the product of both Ca and phosphate, but only a transitory decrease in serum parathyroid hormone levels. The ulcerations were completely healed after 2 months of treatment. Cinacalcet was discontinued after 18 months, but multiple
Bennis, Y; Becquart, C; Aljudaibi, N; Patenotre, P; Guerreschi, P; Delaporte, E; Duquennoy-Martinot, V
Calciphylaxis or calcific arteriolopathy is a rare, life-threatening obstructive pathology of the small cutaneous and subcutaneous vessels. It mainly affects patients with chronic renal failure but it also has been described in patients with normal renal function. The principal risks factors apart from renal failure and phosphocalcic metabolism imbalance are: the female sex, obesity, peripheral vascular disease, diabetes and oral anti-coagulation. We present a very rare case of abdominal, mammarian and upper thighs calciphylaxis in a patient with normal renal function. She presented a severe obesity with a recent important loss of weight and had been treated by oral anticoagulants for a long time. She benefited of a multidisciplinary approach with dermatologists, plastic surgeons and anesthesists permitting a recovery in fourteen weeks. Multidisciplinary approach is necessary but the place of the surgery is not well defined. We report a case in which early and wide surgical approach permitted to obtain a favourable evolution of the pathology. Then, we propose a therapeutic strategy after review of the literature.
Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate
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.
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.
Martínez-Martínez, Marco Ulises; Román-Acosta, Susana; Alvarez-Reyes, Juan Manuel; Oros-Ovalle, Cuauhtémoc; Abud-Mendoza, Carlos
Introducción: la gota es una artropatía inflamatoria que frecuentemente se asocia con obesidad, consumo de alcohol, hipertensión e hipertrigliceridemia. La calcifilaxis se caracteriza por la calcificación metastásica de los vasos de mediano y pequeño calibre. En forma independiente ambas se asocian con mortalidad elevada. Cuando la hiperuricemia y la calcifilaxis están presentes, el riesgo de muerte es de 80%. Caso clínico: hombre de 51 años de edad, con antecedentes de alcoholismo e hipertensión arterial sistémica, quien desarrolló úlceras en extremidades, edema generalizado y síndrome urémico. Tres semanas después de su ingreso falleció debido a sepsis ocasionada por Staphylococcus aureus. El diagnóstico fue calcifilaxis asociada con síndrome metabólico, comorbilidades, factores de riesgo cardiovascular y de insuficiencia renal. Conclusiones: la hiperuricemia es parte del complejo que conforma el síndrome metabólico, resultante de factores genéticos y ambientales. Se reconoce que es un factor asociado con la mortalidad cardiovascular, lo que obliga a considerar a la hiperuricemia en las guías de práctica clínica en la prevención y tratamiento de enfermedades con alta mortalidad debido a las complicaciones que se presentan.
Yderstraede, Knud Bonnet; Clemmensen, Ole; Nielsen, Anna Marie;
due to co-morbidity. Calciphylaxis seems to be preventable by optimized control of calcium-phosphorous metabolism in susceptible individuals. New and promising therapies are evolving. It is important to focus on this condition in order to provide the relevant therapy to the affected cases...
Connor-Stroud, Fawn R; Hopkins, William D.; Preuss, Todd M.; Johnson, Zachary; Zhang, Xiaodong; Sharma, Prachi
Spontaneous vascular mineralization (deposition of iron or calcium salts) has been observed in marble brain syndrome, mineralizing microangiopathy, hypothyroidism, Fahr syndrome, Sturge–Weber syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and calciphylaxis in humans and as an aging or idiopathic lesion in the brains of horses, cats, nonhuman primates, mice, rats, cattle, white-tailed deer, and dogs. Here we present a 27-y-old, adult male ...
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...
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.
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.
Chen, Neal X., E-mail: email@example.com [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
Fatma, Lilia Ben; El Ati, Zohra; Azzouz, Haifa; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hédi Ben; Béji, Soumaya; Zouaghi, Karim; Zitouna, Moncef; Moussa, Fatma Ben
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 subcutaneous 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 nadroparin 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 calciphylaxis, outcome is favorable. PMID:25193911
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.
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.
Usman Hammawa Malabu
Full Text Available Background. Calcific uremic arteriolopathy (CUA or calciphylaxis though generally noted for its high mortality, recent case reports have shown promising results using single agent therapies. However, it is not clear whether combination therapeutic agents will improve course of the disease. Objective. To determine clinical outcome in subjects with CUA on multimodal treatment. Methods. All patients with end-stage renal failure (ESRF at The Townsville Hospital, Australia, from April 1, 2006, to March 31, 2011, with diagnosis of CUA were retrospectively studied. Results. Six subjects with CUA (4 females and 2 males were on various combination therapeutic agents comprising sodium thiosulphate, hyperbaric oxygen, prednisolone, cinacalcet, and parathyroidectomy in addition to intensified haemodialysis, specialist local wound care, and antibiotics. The wounds failed to heal in 3 patients while 5 of the 6 subjects died; cause of death being sepsis in 3 and myocardial infarction in 2. Conclusion. Prognosis of CUA remains poor in spite of multimodal combination therapy. Further prospective studies on a larger population are needed to verify our findings.
Connor-Stroud, Fawn R; Hopkins, William D; Preuss, Todd M; Johnson, Zachary; Zhang, Xiaodong; Sharma, Prachi
Spontaneous vascular mineralization (deposition of iron or calcium salts) has been observed in marble brain syndrome, mineralizing microangiopathy, hypothyroidism, Fahr syndrome, Sturge–Weber syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and calciphylaxis in humans and as an aging or idiopathic lesion in the brains of horses, cats, nonhuman primates, mice, rats, cattle, white-tailed deer, and dogs. Here we present a 27-y-old, adult male chimpanzee (Pan troglodytes) with spontaneous, extensive vascular mineralization localized solely to the brain. The chimpanzee exhibited tremors and weakness of the limbs, which progressed to paralysis before euthanasia. Magnetic resonance brain imaging in 2002 and 2010 (immediately before euthanasia) revealed multiple hypointense foci, suggestive of iron- and calcium-rich deposits. At necropsy, the brain parenchyma had occasional petechial hemorrhage, and microscopically, the cerebral, cerebellar and brain stem, gray and white matter had moderate to severe mural aggregates of a granular, basophilic material (mineral) in the blood vessels. In addition, these regions often had moderate to severe medial to transmural deposition of mature collagen in the blood vessels. We ruled out common causes of brain mineralization in humans and animals, but an etiology for the mineralization could not be determined. To our knowledge, mineralization in brain has been reported only once to occur in a chimpanzee, but its chronicity in our case makes it particularly interesting. PMID:24956215
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
Fein, P A; Madane, S J; Jorden, A; Babu, K; Mushnick, R; Avram, M M; Grosman, I
Protein malnutrition is now well established as an important contributory factor to the high mortality in peritoneal dialysis (PD) patients. Low dietary protein calorie intake is one of the factors leading to protein malnutrition. If PD patients develop difficulty eating, percutaneous endoscopic gastrostomy (PEG) feeding may prove beneficial in providing adequate nutrition. Studies on the effectiveness of PEG feeding in PD patients are limited to pediatric patients. The objective of the present study was to assess the outcome of PEG feeding in adult patients with end-stage renal disease (ESRD) on PD. We retrospectively reviewed charts from May 1992 to February 2000 of 10 consecutive patients in our center who had had feeding tubes inserted. The patients' ages ranged from 37 to 81 years, with mean age of 65. Of the 10 patients, 7 were male, 5 were diabetic, and 1 was infected with the human immunodeficiency virus. Two patients had cerebrovascular accident (CVA) with dysphagia, 3 had multi-infarct dementia, 2 had anoxic encephalopathy, 2 had dementia, and 1 had calciphylaxis with anorexia. Of the 10 patients, 9 failed to eat because of neurologic disorders. Two patients who had functioning PEG feedings before starting PD had no complications. Only 2 of 8 patients already on PD continued with long-term PD after a PEG was inserted. Both patients whose PD was not interrupted at the time of PEG placement immediately developed peritonitis. Of the 6 patients who were maintained on hemodialysis (HD), 2 developed peritonitis within one week of starting PEG feedings. The other 4 had no complications from PEG feedings while being maintained on HD, but 1 developed peritonitis when PD was resumed. Of the 5 patients who developed peritonitis, 3 experienced fungal peritonitis. In PD patients, PEG feeding is associated with frequent complications. However, PEG placement prior to PD initiation appears to be safe. Maintaining patients on HD for at least 6 weeks appears to decrease