Nephrogenic systemic fibrosis is a rare syndrome that involves fibrosis of the skin, joints, eyes, and internal organs. NSF is caused by exposure to gadolinium in gadolinium-based MRI contrast agents (GBCAs) in patients with impaired kidney function. Epidemiological studies suggest that the incidence of NSF is unrelated to gender or ethnicity and it is not thought to have a genetic basis. After GBCAs were identified as a cause of the disorder in 2006, and screening and prevention measures put in place, it is now considered rare.
31-518: NFD may refer to: Nephrogenic fibrosing dermopathy , a medical condition Newfoundland dollar , the currency of the Dominion of Newfoundland from 1865 to 1949. Nifedipine Northfield railway station , England (National Rail code: NFD) Northern Frontier District , Kenya Normalization Form Canonical Decomposition , one of the forms of Unicode normalization Nürnberger Flugdienst , one of
62-558: A differential diagnosis in any patient who has been exposed to a GBCA, regardless of the kidney function level. Three GBCAs have been principally implicated in NSF: gadodiamide , gadopentetate dimeglumine , and gadoversetamide , though cases have been reported with majority of GBCAs on the market. High doses in individual GBCA administrations and high cumulative doses of GBCA over the lifetime of patients with renal dysfunction are associated with increased risk of NSF. De-chelation of Gd(III)
93-618: A legally binding decision issued by The European Commission and applicable in all EU Member States (Commission decision date: 23/11/2017), Intravenous Magnevist and Omniscan is now no longer authorised for use in Europe. Magnavist is, however, still authorised in Europe as an intra-articular MR contrast medium. The authorised indication for the use of linear chelated media gadobenic acid (also known as gadobenate dimeglumine; MultiHance) and gadoxetic acid (Primovist) has been limited to delayed phase liver imaging only. Fibroblast A fibroblast
124-633: A process called epithelial-mesenchymal transition . Conversely, fibroblasts in some situations may give rise to epithelia by undergoing a mesenchymal to epithelial transition and organizing into a condensed, polarized, laterally connected true epithelial sheet. This process is seen in many developmental situations (e.g. nephron and notocord development), as well as in wound healing and tumorigenesis. Fibroblasts make collagen fibers, glycosaminoglycans , reticular and elastic fibers . The fibroblasts of growing individuals divide and synthesize ground substance. Tissue damage stimulates fibrocytes and induces
155-761: Is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen , produces the structural framework ( stroma ) for animal tissues , and plays a critical role in wound healing . Fibroblasts are the most common cells of connective tissue in animals. Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli . Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum (RER). Inactive fibroblasts, called ' fibrocytes ', are smaller, spindle-shaped, and have less RER. Although disjointed and scattered when covering large spaces, fibroblasts often locally align in parallel clusters when crowded together. Unlike
186-399: Is also supported by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn deficiency. Under the transmetallation hypothesis, we can expect that subtle changes in formulation can affect the intrinsic safety of gadolinium complexes, which is indeed observed. There is no specific imaging finding for NSF, and
217-560: Is believed to be unique to patients exposed to gadolinium, although not necessarily limited to areas involved by NSF. The differential diagnoses for NSF include diffuse cutaneous or limited cutaneous systemic sclerosis, scleromyxedema, lipodermatosclerosis, scleroedema diabeticorum, graft versus host disease, eosinophilic fasciitis; eosinophilia-myalgia syndrome; porphyria cutanea tarda, and other disorders. The nearly universal absence of facial skin involvement in NSF, presence of yellow plaques on
248-459: Is different from Wikidata All article disambiguation pages All disambiguation pages Nephrogenic fibrosing dermopathy Clinical features of NSF develop within days to months and, in some cases, years following exposure to some GBCAs. The main symptoms are the thickening and hardening of the skin associated with brawny hyperpigmentation, typically presenting in a symmetric fashion. The skin gradually becomes fibrotic and adheres to
279-415: Is responsible for the toxicity associated with gadolinium complexes such as GBCAs, and the toxicity appears to be a consequence of Zn , Cu , and Ca transmetallation in vivo. This hypothesis is supported by acute toxicity experiments, which demonstrate that despite a 50-fold range of LDse values for four Gd(III) complexes, all become lethally toxic when they release precisely the same quantity of Gd(III). It
310-439: The epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina components in some situations (e.g. subepithelial myofibroblasts in intestine may secrete the α-2 chain-carrying component of the laminin , which is absent only in regions of follicle-associated epithelia which lack
341-624: The ground substance and a variety of fibers . The composition of the ECM determines the physical properties of connective tissues. Like other cells of connective tissue, fibroblasts are derived from primitive mesenchyme . Hence, they express the intermediate filament protein vimentin , a feature used as a marker to distinguish their mesodermal origin. However, this test is not specific as epithelial cells cultured in vitro on adherent substratum may also express vimentin after some time. In certain situations, epithelial cells can give rise to fibroblasts,
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#1732772663846372-408: The ECM remodeling. ECM remodeling is described as changes in the ECM as a result of enzyme activity which can lead to degradation of the ECM. Immune regulation of tumors is largely determined by ECM remodeling because the ECM is responsible for regulating a variety of functions, such as proliferation, differentiation, and morphogenesis of vital organs. In many tumor types, especially those related to
403-524: The MRI exam is recommended for patients already in dialysis treatment, but there is no evidence for introducing dialysis in non-dialytic patients for prevention of NSF. Screening for impaired kidney function is routinely conducted and has drastically reduced the incidence of NSF. Multiple therapies for NSF have been attempted, with variable clinical improvement. None have been as effective as restoration of kidney function. Restoration of kidney function by treating
434-437: The body express many genes that code for immune mediators and proteins. These mediators of immune response enable the cellular communication with hematopoietic immune cells. The immune activity of non-hematopoietic cells, such as fibroblasts, is referred to as “structural immunity”. In order to facilitate a fast response to immunological challenges, fibroblasts encode crucial aspects of the structural cell immune response in
465-550: The contrast agent Omniscan , the Norwegian medical company Nycomed admitted that they were aware of some dangers from using gadolinium-based agents in their product. With both Gadopentetic acid (gadopentetate dimegulumine (Magnevist)) and Gadodiamide (Omniscan) the risk was considered to outweigh the benefits and, as a result, the EMA recommended the licence for intravenous gadopentetic acid and Gadodiamide be suspended. Following
496-485: The development of clinical-grade products. In view of the potential clinical applications of stem cell-derived tissues or primary epithelial cells, the use of human fibroblasts as an alternative to MEF feeders has been studied. Whereas the fibroblasts are usually used to maintain pluripotency of the stem cells, they can also be used to facilitate development of the stem cells into specific type of cells such as cardiomyocytes. Fibroblasts from different anatomical sites in
527-471: The diagnosis is a clinicopathological one, based on presentation and histological findings. At the microscopic level, NSF shows a proliferation of dermal fibroblasts and dendritic cells , thickened collagen bundles, increased elastic fibers , and deposits of mucin . More recent case reports have described the presence of sclerotic bodies (also known as elastocollagenous balls) in skin biopsies from NSF patients. While not universally present, this finding
558-556: The epithelial cells, ECM remodeling is common. Examples of TAF-derived ECM components include Tenascin and Thrombospondin-1 (TSP-1), which can be found in sites of chronic inflammation and carcinomas, respectively. Immune regulation of tumors can also occur through the TAF-derived modulators. Although these modulators may sound similar to the TAF-derived ECM components, they differ in the sense that they are responsible for
589-514: The invasive microorganisms. Receptors on the surface of fibroblasts also allow regulation of hematopoietic cells and provide a pathway for immune cells to regulate fibroblasts. Fibroblasts, like tumor-associated host fibroblasts (TAF), play a crucial role in immune regulation through TAF-derived ECM components and modulators. TAF are known to be significant in the inflammatory response as well as immune suppression in tumors. TAF-derived ECM components cause alterations in ECM composition and initiate
620-417: The location and tissue context where they had previously resided, at least over a few generations. This remarkable behavior may lead to discomfort in the rare event that they stagnate there excessively. The main function of fibroblasts is to maintain the structural integrity of connective tissues by continuously secreting precursors of the extracellular matrix (ECM), providing all such components, primarily
651-694: The lungs and liver. NSF is an iatrogenic disease caused by exposure to gadolinium-based contrast agents used in magnetic resonance imaging. Impaired kidney function reduces the clearance of GBCAs and is the major risk factor for the development of NSF. The etiology or duration of renal failure seems not to be relevant, but NSF risk greatly depends on the residual kidney function. The majority of NSF cases have been identified in patients with stage 5 CKD, but NSF has also developed in patients with stage 4 and 3 CKD, and those with acute kidney injury , even if kidney function subsequently returned to normal following GBCA administration. Thus NSF should be considered as
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#1732772663846682-403: The myofibroblast lining). Fibroblasts can also migrate slowly over substratum as individual cells, again in contrast to epithelial cells. While epithelial cells form the lining of body structures, fibroblasts and related connective tissues sculpt the "bulk" of an organism. The life span of a fibroblast, as measured in chick embryos, is 57 ± 3 days. Fibroblasts and fibrocytes are two states of
713-418: The production of fibroblasts. Besides their commonly known role as structural components, fibroblasts play a critical role in an immune response to a tissue injury. They are early players in initiating inflammation in the presence of invading microorganisms. They induce chemokine synthesis through the presentation of receptors on their surface. Immune cells then respond and initiate a cascade of events to clear
744-481: The regional airlines that merged to form Eurowings Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title NFD . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=NFD&oldid=1141779460 " Category : Disambiguation pages Hidden categories: Short description
775-553: The same cells, the former being the activated state, the latter the less active state, concerned with maintenance and tissue metabolism. Currently, there is a tendency to call both forms fibroblasts. The suffix "-blast" is used in cellular biology to denote a stem cell or a cell in an activated state of metabolism . Fibroblasts are morphologically heterogeneous with diverse appearances depending on their location and activity. Though morphologically inconspicuous, ectopically transplanted fibroblasts can often retain positional memory of
806-418: The sclera of the eyes, absence of Raynaud's phenomenon, and other differences in presentation can aid the proper diagnosis. History of exposure to GBCAs would favor NSF as the differential diagnosis. The only known measure for prevention of NSF is the non-use or cautious use of GBCAs in patients with renal impairment, including preferential use of safer, macrocyclic GBCAs. Performing dialysis immediately after
837-558: The underlying disease process, recovery from acute kidney injury (AKI), or performing a kidney transplant can slow or hold the progression of NSF. A few cases of curative kidney transplantation have been reported, and it is appropriate to consider transplantation as treatment. NSF affects males and females in approximately equal numbers and has been reported in patients of different ethnic and geographic regions. It most often affects middle-aged individuals, but there are reports of cases occurring from childhood to senescence. This condition
868-425: The underlying fascia. The symptoms initiate distally in the limbs and progress proximally, sometimes involving the trunk. Joint contractures of the fingers, elbows and knees can develop secondary to skin involvement and can severely impair physical function. While skin involvement is on the foreground, the process may involve any organ, e.g., the eye, heart, diaphragm, pleura, pericardium, and kidneys, as well as
899-584: The variation and turnover of the ECM. Cleaved ECM molecules can play a critical role in immune regulation. Proteases like matrix metalloproteineases and the uPA system are known to cleave the ECM. These proteases are derived from fibroblasts. Mouse embryonic fibroblasts (MEFs) are often used as supportive "feeder cells" in research using human embryonic stem cells, induced pluripotent stem cells and primary epithelial cell culture. However, many researchers are trying to phase out MEFs in favor of culture media with precisely defined ingredients in order to facilitate
930-504: Was first described as an independent disease entity in 2000. In 2006, the link between NSF and gadolinium-based MRI contrast agents was made. As a result, restrictions on use of GBCAs in patients with an estimated glomerular filtration rate (a measure of kidney function ) under 60 and especially under 30 mL/min/1.73 m have been recommended and NSF is now considered rare. After several years of controversy, during which up to 100 Danish patients developed gadolinium poisoning after use of
961-456: Was originally termed "nephrogenic fibrosing dermopathy" as initially only skin involvement in patients with impaired kidney function was observed, and later renamed "nephrogenic systemic fibrosis" to better describe its systemic nature. The term "gadolinium-associated systemic fibrosis" has also been proposed to reflect the fact that impaired kidney function is not in itself the cause of NSF. The first cases of NSF were identified in 1997, but it