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      Calciphylaxis in chronic, non-dialysis-dependent renal disease

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      1 , , 2 , 3 , 1
      BMC Nephrology
      BioMed Central

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          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.

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          Most cited references8

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          Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.

          The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Post hoc analysis. The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. 980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration 0.2 for the difference). In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
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            Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein–deficient Mice

            Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN in vascular calcification, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice. Mice deficient in MGP alone (MGP−/− OPN+/+) showed calcification of their arteries as early as 2 weeks (wk) after birth (0.33 ± 0.01 mmol/g dry weight), and the expression of OPN in the calcified arteries was greatly up-regulated compared with MGP wild-types. OPN accumulated adjacent to the mineral and colocalized to surrounding cells in the calcified media. Cells synthesizing OPN lacked smooth muscle (SM) lineage markers, SM α-actin and SM22α. However, most of them were not macrophages. Importantly, mice deficient in both MGP and OPN had twice as much arterial calcification as MGP−/− OPN+/+ at 2 wk, and over 3 times as much at 4 wk, suggesting an inhibitory effect of OPN in vascular calcification. Moreover, these mice died significantly earlier (4.4 ± 0.2 wk) than MGP−/− OPN+/+ counterparts (6.6 ± 1.0 wk). The cause of death in these animals was found to be vascular rupture followed by hemorrhage, most likely due to enhanced calcification. These studies are the first to demonstrate a role for OPN as an inducible inhibitor of ectopic calcification in vivo.
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              Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment.

              Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis, and thrombosis. This syndrome occurs predominantly in individuals with renal failure and results in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscle. The syndrome causes significant morbidity in the form of infection, organ failure, and pain. Mortality rates are high. In individuals with renal failure, risk factors for the development of calciphylaxis include female sex, Caucasian race, obesity, and diabetes mellitus. Many cases occur within the first year of dialysis treatment. Several recent reports demonstrate that prolonged hyperphosphatemia and/or elevated calcium x phosphorus products are associated with the syndrome. Protein malnutrition increases the likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or protein S deficiency. Recent advances in diagnostic tools and therapeutic strategies have helped in the management of patients with calciphylaxis.
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                Author and article information

                Journal
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                2003
                29 September 2003
                : 4
                : 8
                Affiliations
                [1 ]Department of Nephrology, University of Leipzig, Phillip-Rosenthal-Str. 27, Leipzig, Germany
                [2 ]Department of Pathology, University of Leipzig, Liebig-Str. 26, Leipzig, Germany
                [3 ]Internal-Medicine Department III, University of Leipzig, Phillip-Rosenthal-Str. 27, Leipzig, Germany
                Article
                1471-2369-4-8
                10.1186/1471-2369-4-8
                222929
                14514359
                83544f6d-2a5c-49d1-ae28-c081d901db98
                Copyright © 2003 Pliquett et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
                History
                : 26 May 2003
                : 29 September 2003
                Categories
                Case Report

                Nephrology
                Nephrology

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