Materiały źródłowe

• #1 What Causes Nephrogenic Systemic Fibrosis? – The Rheumatologist

  https://www.the-rheumatologist.org/article/what-causes-nephrogenic-systemic-fibrosis/?singlepage=1

  What Causes Nephrogenic Systemic Fibrosis? […] In August 2001, Diane Endicott noted the spontaneous onset of tightening of the skin over her feet and lower legs. […] Endicott’s nephrologist was puzzled by the rapid onset of this scleroderma-like condition, having never seen this before among the other patients receiving dialysis under his care. […] They concluded that each patient had developed a novel skin disease that they named nephrogenic fibrosing dermopathy. […] Because fibrosis was subsequently observed in other organs, this entity has been renamed nephrogenic systemic fibrosis (NSF). […] All patients who developed NSF had abnormal renal function at some time before the onset of skin changes, although this was not required by the case definition. […] This observation raised the possibility that an environmental exposure might trigger the onset of NSF in patients with chronic kidney disease.

• #2 Nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis? What we know and what we have to learn | Nefrología

  https://revistanefrologia.com/en-nephrogenic-fibrosing-dermopathy-or-nephrogenic-systemic-fibrosis-what-we-know-articulo-X2013251409004869

  La Fibrosis Sistmica Nefrognica (FSN) fue descrita por primera vez como entidad singular en el ao 1997, y despus se confirm y document en la literatura mdica durante el ao 2000 como una enfermedad escleromixedematosa fibrosante que se presentaba en pacientes con afecciones renales. […] La prevencin, el diagnstico precoz y el tratamiento son esenciales para limitar su impacto, siendo el fracaso renal agudo y la enfermedad renal crnica, junto con la administracin de agentes de contraste que contienen Gadolinio (GD) los factores de riesgo ms importantes que pueden hacer desarrollar la enfermedad. […] Nephrogenic systemic fibrosis (NSF) was first recognized as a unique entity in 1997 and subsequently defined in the literature in 2000 as a novel fibrosing disorder occurring in the setting of renal disease.

• #3 Nephrogenic Systemic Fibrosis – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33620831/

  Nephrogenic systemic fibrosis (NSF) is a progressive multiorgan fibrosing condition caused by exposure to gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI) in the setting of low glomerular filtration rate (GFR). […] NSF occurs in patients with acute or severe chronic renal failure, usually stage 4 or 5 chronic kidney disease (CKD), but it has also been described in patients with stage 3 CKD. […] The condition was initially called nephrogenic fibrosing dermopathy due to the cutaneous manifestation. Still, the terminology changed to gadolinium-induced fibrosis or NSF as more systemic manifestations came to light.

• #4 Nephrogenic Systemic Fibrosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK567754/

  Nephrogenic systemic fibrosis (NSF) is a rare yet serious fibrosing disorder primarily affecting patients with impaired renal function who have been exposed to gadolinium-based contrast agents during magnetic resonance imaging. […] Nephrogenic systemic fibrosis (NSF) is a progressive multiorgan fibrosing condition caused by exposure to gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI) in the setting of low glomerular filtration rate (GFR). […] The condition was first described in 2000 when several physicians across the United States (US) noted patients with a scleroderma-type illness, and the association with GBCA administration in the setting of renal failure was solidified as more cases were presented. […] The prevailing theory is that Gd exposure is prolonged in patients with renal disease, allowing the Gd to dissociate from its organic chelators and bind with calcium, phosphate, and other endogenous compounds to deposit in the skin and tissues.

• #5 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mriquestions.com/what-is-nsf.html

  Nephrogenic systemic fibrosis (NSF) is a rare, progressive, often fatal disease characterized by skin thickening, painful joint contractures, and fibrosis of multiple organs including the lungs, liver, muscles, and heart. Nearly all documented cases have occurred in patients with chronic severe renal insufficiency who have received gadolinium contrast. The association between gadolinium and NSF was first reported by Danish nephrologists in 2006. Between 2006 and 2010 several hundred cases were diagnosed worldwide. […] NSF usually develops clinically within days to months following gadolinium exposure, although rare cases have been reported years later. Nearly all patients have been in various degrees of renal failure and many were on dialysis. Only exceedingly rare cases have been reported in patients with eGFRs 30 mL/min/1.73m. High and/or multiple doses of contrast are frequently reported, as are the use of linear contrast agents (ACR Group I). Other risk factors include liver disease and acidosis. Nephrogenic Systemic Fibrosis (NSF)

• #6 What Causes Nephrogenic Systemic Fibrosis? – The Rheumatologist

  https://www.the-rheumatologist.org/article/what-causes-nephrogenic-systemic-fibrosis/?singlepage=1

  Between 2003 and 2005, Thomas Grobner, MD, a nephrologist at the General Hospital of Wiener Neustadt, Austria, observed that five of nine patients receiving hemodialysis under his care developed skin changes of NSF within two to four weeks after undergoing magnetic resonance (MR) angiography with gadodiamide contrast. […] Shortly thereafter, Peter Marckmann, MD, of the department of nephrology, and colleagues from Copenhagen University Hospital at Herlev, Denmark, reported on 13 patients who also developed NSF following exposure to gadodiamide contrast during MR imaging. […] The strong association between NSF and prior exposure to gadolinium-containing contrast agents suggests that this condition might be prevented by not exposing patients with chronic kidney disease to gadolinium. […] Future studies should be directed toward understanding the molecular mechanism by which fibrosis occurs following gadolinium exposure in patients with underlying chronic kidney disease and targeting that mechanism with specific therapies that will prevent development of and reverse fibrosis.

• #7 What Causes Nephrogenic Systemic Fibrosis? – The Rheumatologist

  https://www.the-rheumatologist.org/article/what-causes-nephrogenic-systemic-fibrosis/?singlepage=1

  Between 2003 and 2005, Thomas Grobner, MD, a nephrologist at the General Hospital of Wiener Neustadt, Austria, observed that five of nine patients receiving hemodialysis under his care developed skin changes of NSF within two to four weeks after undergoing magnetic resonance (MR) angiography with gadodiamide contrast. […] Shortly thereafter, Peter Marckmann, MD, of the department of nephrology, and colleagues from Copenhagen University Hospital at Herlev, Denmark, reported on 13 patients who also developed NSF following exposure to gadodiamide contrast during MR imaging. […] The strong association between NSF and prior exposure to gadolinium-containing contrast agents suggests that this condition might be prevented by not exposing patients with chronic kidney disease to gadolinium. […] Future studies should be directed toward understanding the molecular mechanism by which fibrosis occurs following gadolinium exposure in patients with underlying chronic kidney disease and targeting that mechanism with specific therapies that will prevent development of and reverse fibrosis.

• #8

  https://journals.lww.com/jasn/fulltext/2006/09000/nephrogenic_systemic_fibrosis__suspected_causative.6.aspx

  Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. […] This study therefore reviewed all of the authors confirmed cases of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. […] Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P 0.0001). […] These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis.

• #9 Nephrogenic systemic fibrosis – Wikipedia

  https://en.wikipedia.org/wiki/Nephrogenic_systemic_fibrosis

  NSF is caused by exposure to gadolinium in gadolinium-based MRI contrast agents (GBCAs) in patients with impaired kidney function. […] 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. […] 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. […] 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.

• #10

• #11 Nephrogenic Systemic Fibrosis

  https://www.medscape.com/viewarticle/714922

  These are the two contrast agents most commonly associated with the subsequent development of NSF among individuals with stage 5 CKD. […] Gadolinium has been detected and quantified in biopsy specimens from patients with NSF, initially in skin and subsequently in other tissues (High et al, 2007). […] In addition to the strong epidemiologic association between NSF and prior gadolinium-containing contrast agent exposure, an inverse relationship exists between cumulative exposure and time to onset of NSF after the most recent dose of a gadolinium-containing contrast agent: NSF signs and symptoms develop more rapidly after exposure to a gadolinium-containing contrast agent in patients who previously had received larger cumulative volumes of these contrast agents (Abujudeh et al, 2009). […] It is hypothesized that, following the administration of gadolinium-containing contrast agents to individuals with CKD, gadolinium may be released from the polyamino-polycarboxylic ligands with which it is chelated.

• #12 Nephrogenic Systemic Fibrosis as a Complication after Gadolinium-Containing Contrast Agents: A Rapid Review

  https://www.mdpi.com/1660-4601/18/6/3000

  Due to the high risk of NSF development after exposure to these two contrast agents, their use has become a contraindication in patients with stage 4 and 5 chronic kidney disease (CKD). […] The hypothesis that gadolinium contrast agents are related to the development of NSF was put forward for the first time by Grobner et al., in 2006. […] Many authors emphasized that the highest risk of NSF exists in patients with a GFR < 15 mL/min/1.73 m² (i.e., chronic kidney disease at stage 5). [...] Metabolic acidosis, ongoing inflammatory process, treatment with erythropoietin and high serum concentrations of calcium and phosphorus have been reported as factors contributing to the development of NSF. [...] The implementation of the recommendations and changes in hospital policy have contributed to virtually eliminating this complication. [...] More recent guidelines and reports show that not all contrast agents have the same risk of triggering NFS. [...] The risk of developing NSF is almost as small as the risk of developing an allergic reaction after contrast application.

• #13 Nephrogenic systemic fibrosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/nephrogenic-systemic-fibrosis?embed_domain=external.radpair.comradiopaedia-icon-144.pngradiopaedia-icon-144.pngfavicon.ico&lang=us

  Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy, occurs almost exclusively in patients with renal impairment and is associated with the administration of gadolinium-based contrast agents (GBCAs) used in MRI. […] Low-stability gadolinium contrast media show the strongest association with nephrogenic systemic fibrosis. A literature review has shown that ~78% of all unconfounded, single-agent cases of nephrogenic systemic fibrosis have been associated with Omniscan (gadodiamide), while ~20% have been associated with Magnevist (gadopentetate dimeglumine), and less than 2% with OptiMARK (gadoversetamide), all of which are group I GBCAs. […] The development of nephrogenic systemic fibrosis with exposure to group I gadolinium-containing MRI contrast agents has been strongly reported in patients with moderate to end-stage renal impairment. This could be due to transmetallation, which is the replacement of the gadolinium from the chelate and forming a free gadolinium ion, free gadolinium ions may then deposit in different tissues and result in inflammation and fibrosis. Prolonged clearance times of gadolinium-based contrast agents in significant renal insufficiency contribute to this transmetallation process.

• #14 Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines

  https://consultqd.clevelandclinic.org/gadolinium-induced-nephrogenic-systemic-fibrosis-classification-risk-and-guidelines

  By 2009, the disease was well established, and the US Food and Drug Administration (FDA) had received over 500 reports, most of them from the United States and Denmark. In response to this crisis, the authorities and radiology societies were quick to react. In 2007, both the FDA and the European Medicine Agency issued warnings highlighting the risk of NSF associated with the use of gadolinium-based contrast agents. Gadolinium agents that have a linear molecular shape pose a higher risk, and their use was contraindicated in patients with acute and severe chronic kidney disease with eGFRs less than 30 mL/min/1.73 m2, as well as in patients on dialysis. […] As a result of those measures, the number of cases of NSF was drastically reduced. The last reported case in the United States dates back to 2010, and the last report in the world was in 2012. Gadolinium-based contrast agents have been used since the 1980s and were initially thought to have an excellent safety profile. However, their incriminating role in NSF highlighted their potential toxicity.

• #15 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mri-q.com/what-is-nsf.html

  The strong association with renal insufficiency most likely relates to the prolonged biological half-life due to prolonged excretion of gadolinium. However, other factors have been imputed, including metabolic acidosis; elevated iron and phosphate levels; erythropoietin therapy; vasculopathy; and infectious/inflammatory mediators. […] The pathogenesis of NSF is believed to begin with the displacement of the Gd ion from its chelate by another metallic cation (Fe+3, Zn+2, or Ca+2) through a so-called transmetalation reaction: (Metal ion) + Gd-Chelate Metal-Chelate + Gd+3. The free Gd ion is then deposited in the skin and other soft tissues. There it is engulfed by CD163+ iron-recycling and other macrophages creating an inflammatory response and cytokine release. Circulating fibrocytes (immunologically unique CD-34 positive cells derived from bone marrow) deposit in tissue, transforming into spindle cells that proliferate and become the hallmark of the disease. Following recognition of this disorder and its association with gadolinium in patients with renal insufficiency, the worldwide radiology community responded immediately to put an end to this iatrogenic disease. Today, NSF has been nearly completely eliminated due to these measures. In more recent times, however, gadolinium-induced plaques have been reported in the extremities not meeting the full criteria for NSF. The story of NSF is sad one that we radiologists created. It should serve as a lesson that even drugs which appear to be extraordinarily safe may not be infinitely safe for all patients. Sometimes adverse effects may be subtle, disguised, or appear at long time intervals following administration. NSF is thus a call and reminder to be forever vigilant.

• #16 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mri-q.com/what-is-nsf.html

  The strong association with renal insufficiency most likely relates to the prolonged biological half-life due to prolonged excretion of gadolinium. However, other factors have been imputed, including metabolic acidosis; elevated iron and phosphate levels; erythropoietin therapy; vasculopathy; and infectious/inflammatory mediators. […] The pathogenesis of NSF is believed to begin with the displacement of the Gd ion from its chelate by another metallic cation (Fe+3, Zn+2, or Ca+2) through a so-called transmetalation reaction: (Metal ion) + Gd-Chelate Metal-Chelate + Gd+3. The free Gd ion is then deposited in the skin and other soft tissues. There it is engulfed by CD163+ iron-recycling and other macrophages creating an inflammatory response and cytokine release. Circulating fibrocytes (immunologically unique CD-34 positive cells derived from bone marrow) deposit in tissue, transforming into spindle cells that proliferate and become the hallmark of the disease. Following recognition of this disorder and its association with gadolinium in patients with renal insufficiency, the worldwide radiology community responded immediately to put an end to this iatrogenic disease. Today, NSF has been nearly completely eliminated due to these measures. In more recent times, however, gadolinium-induced plaques have been reported in the extremities not meeting the full criteria for NSF. The story of NSF is sad one that we radiologists created. It should serve as a lesson that even drugs which appear to be extraordinarily safe may not be infinitely safe for all patients. Sometimes adverse effects may be subtle, disguised, or appear at long time intervals following administration. NSF is thus a call and reminder to be forever vigilant.

• #17 Nephrogenic systemic fibrosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/nephrogenic-systemic-fibrosis?embed_domain=external.radpair.comradiopaedia-icon-144.pngradiopaedia-icon-144.pngfavicon.ico&lang=us

  Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy, occurs almost exclusively in patients with renal impairment and is associated with the administration of gadolinium-based contrast agents (GBCAs) used in MRI. […] Low-stability gadolinium contrast media show the strongest association with nephrogenic systemic fibrosis. A literature review has shown that ~78% of all unconfounded, single-agent cases of nephrogenic systemic fibrosis have been associated with Omniscan (gadodiamide), while ~20% have been associated with Magnevist (gadopentetate dimeglumine), and less than 2% with OptiMARK (gadoversetamide), all of which are group I GBCAs. […] The development of nephrogenic systemic fibrosis with exposure to group I gadolinium-containing MRI contrast agents has been strongly reported in patients with moderate to end-stage renal impairment. This could be due to transmetallation, which is the replacement of the gadolinium from the chelate and forming a free gadolinium ion, free gadolinium ions may then deposit in different tissues and result in inflammation and fibrosis. Prolonged clearance times of gadolinium-based contrast agents in significant renal insufficiency contribute to this transmetallation process.

• #18 Nephrogenic Systemic Fibrosis, Moh’d sharshir | PPT

  https://www.slideshare.net/slideshow/nephrogenic-systemic-fibrosis/101723380

  There is no predilection to NSF by gender, race, or age, etiology of kidney disease; or duration of renal failure. […] However, patients undergoing peritoneal dialysis, compared with hemodialysis, may be at higher risk. […] Gadolinium is hyperosmolal (650 mosmol/kg) contrast agents that are primarily administered during magnetic resonance imaging (MRI) or MR angiography studies. […] There is strong evidence that the risk of NSF is greater with linear than with macrocyclic preparations. […] The pathogenesis of NSF is not fully understood. The resemblance of NSF to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be important, possibly resulting in a cascade of events similar to wound healing. […] The major preventive measure for NSF that can be currently recommended to patients with advanced kidney failure is the avoidance of gadolinium.

• #19 Nephrogenic systemic fibrosis : (nephrogenic fibrosing dermopathy) – Creative Med Doses

  https://creativemeddoses.com/?post_type=topic&p=1048

  The vascular and endothelial injury associated with chronic kidney disease facilitates the gadolinium invasion into the tissues. The accumulated gadolinium chelates with iron and phosphate gets deposited in various tissues/organs. […] The activated macrophages release cytokines and chemokines, some of which stimulate increased production of CD 34 positive fibroblasts in bone marrow. The newly produced fibrocytes come into the circulation and trigger fibrosis of various organs. […] The deep fibrosis of visceral organs and other tissues leads to organ dysfunction and failure.

• #20

  https://step2.medbullets.com/renal/121624/gadolinium-associated-nephrogenic-systemic-fibrosis

  Gadolinium may dissociate from its chelating molecule and increase the exposure in patients with renal failure. […] Gadolinium deposition in tissue may cause a tissue injury reaction. […] This may activate transforming growth factor TGF-1 pathway. […] Gadolinium may also directly increase the number of circulating fibrocytes by stimulating the bone marrow. […] Increased number of fibrocytes can produce collagen and cause tissue fibrosis.

• #21 Nephrogenic Systemic Fibrosis

  https://www.medscape.com/viewarticle/714922

  Increased transforming growth factor (TGF) b1 mRNA immunostaining has been detected in involved skin and muscle from patients with NSF (Jimenez et al, 2004). […] These profibrotic cytokines may then bind to their cognate receptors to stimulate production of collagen and other extracellular matrix (ECM) proteins, resulting in the characteristic features of NSF.

• #22 Nephrogenic Systemic Fibrosis: Is Gadolinium the Missing Piece to the Puzzle? (See Erratum 2008;82:158) | MDedge

  https://mdedge.com/cutis/article/67688/contact-dermatitis/nephrogenic-systemic-fibrosis-gadolinium-missing-piece-puzzle

  On June 8, 2006, the US Food and Drug Administration (FDA) released a public health advisory warning patients and physicians of the possible link between Gd-containing contrast agents and NSF. […] It now appears that Gd also plays a central role in the pathogenesis of NSF. […] Based on these previously reported data, we hypothesize that in the presence of some unclear metabolic alteration, such as acidosis, and renal failure, exposure to high-dose Gd (as in MRA) for prolonged periods of time could result in Gd ion dissociation from its chelator. The Gd ion may precipitate with other anions, such as phosphate, or other metals, such as iron, and deposit in any tissue, resulting in local macrophage recruitment to engulf the elemental Gd. This theory could explain the initial tissue injury and the presence of multinucleated giant cells. […] Ultimately, we propose that NSF may stem from elemental Gd–induced macrophage death.

• #23 Nephrogenic systemic fibrosis following hair-dye ingestion induced acute renal failure – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/nephrogenic-systemic-fibrosis-following-hair-dye-ingestion-induced-acute-renal-failure/

  Subsequently, multiple studies confirmed the gadolinium as the main implicating factor. […] The half-life of gd in patients with normal renal function is 90 minutes, but in patients with impaired renal function, elimination half-life can be prolonged to more than 30 hours. […] It has been suggested that fibrosis and rarely observed calcium deposits in the affected tissue is mediated by transforming growth factor-beta (TGF-beta), a cytokine elaborated by CD34 positive fibrocyte. […] Hair dye ingestion for suicidal purpose though rare in west, is not uncommon in certain parts of the world such as East Africa, middle-east and Indian subcontinent. […] Hair dye induced acute renal failure, hemodialysis and administration of gd containing contrast were probably the likely events which precipitated NSF in our patient.

• #24 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mri-q.com/what-is-nsf.html

  The strong association with renal insufficiency most likely relates to the prolonged biological half-life due to prolonged excretion of gadolinium. However, other factors have been imputed, including metabolic acidosis; elevated iron and phosphate levels; erythropoietin therapy; vasculopathy; and infectious/inflammatory mediators. […] The pathogenesis of NSF is believed to begin with the displacement of the Gd ion from its chelate by another metallic cation (Fe+3, Zn+2, or Ca+2) through a so-called transmetalation reaction: (Metal ion) + Gd-Chelate Metal-Chelate + Gd+3. The free Gd ion is then deposited in the skin and other soft tissues. There it is engulfed by CD163+ iron-recycling and other macrophages creating an inflammatory response and cytokine release. Circulating fibrocytes (immunologically unique CD-34 positive cells derived from bone marrow) deposit in tissue, transforming into spindle cells that proliferate and become the hallmark of the disease. Following recognition of this disorder and its association with gadolinium in patients with renal insufficiency, the worldwide radiology community responded immediately to put an end to this iatrogenic disease. Today, NSF has been nearly completely eliminated due to these measures. In more recent times, however, gadolinium-induced plaques have been reported in the extremities not meeting the full criteria for NSF. The story of NSF is sad one that we radiologists created. It should serve as a lesson that even drugs which appear to be extraordinarily safe may not be infinitely safe for all patients. Sometimes adverse effects may be subtle, disguised, or appear at long time intervals following administration. NSF is thus a call and reminder to be forever vigilant.

• #25 Nephrogenic Systemic Fibrosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK567754/

  Factors contributing to NSF include total gadolinium exposure, hypercalcemia, hyperphosphatemia, high-dose erythropoietin therapy, hepatorenal syndrome, immunosuppression, and vasculopathy. […] Gd has also been shown to be immunogenic in vitro, activating toll-like receptors, macrophages, and dendritic cells. […] The American College of Radiology also has a similar classification system of 3 groups, with group 1 being the highest risk and group 3, the lowest. […] The most debilitating NSF sequelae are the fibrosis of visceral organs such as the heart, lungs, renal tubules, and skeletal muscles. […] Nephrogenic systemic fibrosis is considered a debilitating, progressive disease. This condition causes visceral and cutaneous fibrosis in patients with severe renal insufficiency exposed to GBCAs.

• #26 Gadolinium-Associated Nephrogenic Systemic Fibrosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/1001/p711.html

  Proposed risk factors include severe renal dysfunction, acute renal failure, proinflammatory states (e.g., major surgery, thrombotic events, infection, malignancy), and high-dose erythropoietin use. […] The pathophysiology behind nephrogenic systemic fibrosis is unclear. […] One proposed theory for nephrogenic systemic fibrosis is the transmetallation of the gadolinium and chelating agent. […] This free gadolinium ion may then deposit in tissues. […] Renal failure increases the duration of the gadolinium exposure through decreased clearance of free gadolinium. […] This deposition leads to the recruitment of fibrocytes, which, along with the proinflammatory state, causes tissue injury and further fibrocyte recruitment, ultimately leading to nephrogenic systemic fibrosis.

• #27

• #28 Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media | Nefrología

  https://www.revistanefrologia.com/en-renal-function-nephrogenic-systemic-fibrosis-articulo-X2013251414054390

  Although the exact pathogenesis of NSF continues to be unknown, the only solid association identified in all patients with NSF is renal failure, both in its chronic and acute forms, and its presence is a sine qua non condition for the diagnosis of the disease. […] Given that exposure to GBCM does not explain all cases of NSF, other coadjuvant risk factors have been studied that may contribute to its development, many of them associated with situations of renal failure. […] The two forms, free Gd ions and the chelate-Gd complex may cause the release of cytokines, stimulating skin macrophages (Gd-free ions) or peripheral blood monocytes (chelate-Gd complexes). […] The presence of renal failure contributes to the release of free GD3 by increasing transmetalation in a uraemic environment and decreasing the glomerular filtration rate.

• #29 MRI warning as study says injection could cause deadly material to form in body | The Independent

  https://www.the-independent.com/health-and-wellbeing/mri-scan-chemical-injection-oxalic-acid-gadolinium-b2737760.html

  Scientists say gadolinium-based contrast agents may cause nephrogenic systemic fibrosis, a rare condition leading to the thickening and hardening of the skin, heart, and lungs with painful contracture of the joints. […] Researchers found that oxalic acid caused small amounts of gadolinium to precipitate out of the contrast agent and form nanoparticles that infiltrated the cells of various organs. […] Some patients may be more susceptible to this kind of nanoparticle precipitation due to their metabolism, researchers say. […] It might be if they were in a high oxalic state or a state where molecules are more prone to linking to the gadolinium, leading to the formation of the nanoparticles, Dr Wagner said. […] That might be why some individuals have such awful symptoms and this massive disease response, whereas other people are fine, he explained.

• #30 Nephrogenic Systemic Fibrosis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK567754/

  Factors contributing to NSF include total gadolinium exposure, hypercalcemia, hyperphosphatemia, high-dose erythropoietin therapy, hepatorenal syndrome, immunosuppression, and vasculopathy. […] Gd has also been shown to be immunogenic in vitro, activating toll-like receptors, macrophages, and dendritic cells. […] The American College of Radiology also has a similar classification system of 3 groups, with group 1 being the highest risk and group 3, the lowest. […] The most debilitating NSF sequelae are the fibrosis of visceral organs such as the heart, lungs, renal tubules, and skeletal muscles. […] Nephrogenic systemic fibrosis is considered a debilitating, progressive disease. This condition causes visceral and cutaneous fibrosis in patients with severe renal insufficiency exposed to GBCAs.

• #31 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mriquestions.com/what-is-nsf.html

  Nephrogenic systemic fibrosis (NSF) is a rare, progressive, often fatal disease characterized by skin thickening, painful joint contractures, and fibrosis of multiple organs including the lungs, liver, muscles, and heart. Nearly all documented cases have occurred in patients with chronic severe renal insufficiency who have received gadolinium contrast. The association between gadolinium and NSF was first reported by Danish nephrologists in 2006. Between 2006 and 2010 several hundred cases were diagnosed worldwide. […] NSF usually develops clinically within days to months following gadolinium exposure, although rare cases have been reported years later. Nearly all patients have been in various degrees of renal failure and many were on dialysis. Only exceedingly rare cases have been reported in patients with eGFRs 30 mL/min/1.73m. High and/or multiple doses of contrast are frequently reported, as are the use of linear contrast agents (ACR Group I). Other risk factors include liver disease and acidosis. Nephrogenic Systemic Fibrosis (NSF)

• #32 Nephrogenic Systemic Fibrosis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1097889-overview

  The cause of nephrogenic systemic fibrosis is the connexation of renal insufficiency and gadolinium exposure from imaging studies. The exact degree of renal insufficiency that sets up the development of nephrogenic systemic fibrosis is not known. Risk factors include advanced chronic kidney disease (stages 4 and 5) and acute or chronic inflammatory insults. […] Gadolinium-based contrast agents (Ablavar, Eovist, Magnevist, MultiHance, Omniscan, OptiMARK, ProHance) have recently been linked to the development of nephrogenic systemic fibrosis. The disease has occurred in patients with moderate- to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography. […] On September 9, 2010, the FDA announced it is requiring that gadolinium-based contrast agents (GBCAs) carry new warnings on their labels about the risk for nephrogenic systemic fibrosis and its association when administered to certain patients with kidney disease. The FDA’s review of the safety of the most widely used GBCAs determined that Magnevist, Omniscan, and Optimark are associated with a greater risk for nephrogenic systemic fibrosis than other GBCAs. […] Data suggest that nephrogenic systemic fibrosis may follow the administration of any GBCA, and the FDA continues to assess the safety of each GBCA to better estimate its nephrogenic systemic fibrosis risks.

• #33 Gadolinium-Associated Nephrogenic Systemic Fibrosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2009/1001/p711.html

  Nephrogenic systemic fibrosis is a progressive, potentially fatal multiorgan system fibrosing disease related to exposure of patients with renal failure to the gadolinium-based contrast agents used in magnetic resonance imaging. […] There have been reports of nephrogenic systemic fibrosis developing in patients not exposed to gadolinium-based contrast agents, but most patients have the triad of gadolinium exposure through contrast-enhanced magnetic resonance imaging, renal failure, and a proinflammatory state, such as recent surgery, endovascular injury, or sepsis. […] The mechanism for nephrogenic systemic fibrosis is unclear, and current treatments are disappointing. […] The incidence of nephrogenic systemic fibrosis in patients with severe renal insufficiency following exposure to gadolinium-based contrast agents appears to be approximately 4 percent, without any regard to sex, race, or age.

• #34 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mriquestions.com/what-is-nsf.html

  Nephrogenic systemic fibrosis (NSF) is a rare, progressive, often fatal disease characterized by skin thickening, painful joint contractures, and fibrosis of multiple organs including the lungs, liver, muscles, and heart. Nearly all documented cases have occurred in patients with chronic severe renal insufficiency who have received gadolinium contrast. The association between gadolinium and NSF was first reported by Danish nephrologists in 2006. Between 2006 and 2010 several hundred cases were diagnosed worldwide. […] NSF usually develops clinically within days to months following gadolinium exposure, although rare cases have been reported years later. Nearly all patients have been in various degrees of renal failure and many were on dialysis. Only exceedingly rare cases have been reported in patients with eGFRs 30 mL/min/1.73m. High and/or multiple doses of contrast are frequently reported, as are the use of linear contrast agents (ACR Group I). Other risk factors include liver disease and acidosis. Nephrogenic Systemic Fibrosis (NSF)

• #35 Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines

  https://consultqd.clevelandclinic.org/gadolinium-induced-nephrogenic-systemic-fibrosis-classification-risk-and-guidelines

  The guidelines set by the FDA and the radiology societies were undoubtedly effective in curbing the disease and eventually eliminating it. A recent review of 639 patients with biopsy-proven NSF from 173 articles estimated that the risk of NSF per million exposures had decreased from 2.07 before 2008 to 0.028 afterward. Most cases were associated with exposure to group I agents. […] Although NSF has been basically eradicated since the guidelines were implemented, several cases of NSF have been reported in patients who never were exposed to gadolinium. This suggests that gadolinium-based contrast agents are a major trigger for NSF, but they may not be the only one. Additionally, in recent years, there have been data suggesting that gadolinium can deposit in the brain after repeated exposure to gadolinium-based contrast agents, even in patients with healthy kidneys. The significance of this brain deposition remains unknown, and to date, no adverse health effects have been uncovered.

• #36 Nephrogenic systemic fibrosis: A frivolous entity

  https://www.wjgnet.com/2220-6124/full/v10/i3/29.htm

  Although the true cause of NSF is still unknown; almost all patients who develop NSF have an underlying kidney dysfunction. Approximately 90% of the patients described in the registry have end-stage kidney disease and they are either on hemodialysis or peritoneal dialysis. The remaining patients have some degree of chronic kidney dysfunction or acute kidney injury (AKI). From the previously published literature, it can be estimated that one or more exposures to group 1 GBCA may pose a risk in developing NSF in patients with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2. […] The exact mechanism of NSF is unknown. It is hypothesized that usually a trigger is needed to initiate the fibrosing process and Gd may act as a potential trigger for NSF development in patients with kidney disease. The most widely held hypothesis is that kidney dysfunction impairs the renal excretion of Gd which prolongs its half-life and increases the chance of Gd dissociation from the chelate.

• #37 Nephrogenic Systemic Fibrosis (NSF) Best Nephrologist In Delhi | Dr Rajesh Goel | Kidney Care Centre

  https://www.kidneycarecentre.in/nephrogenic-systemic-fibrosis-nsf/

  Thus, it is assumed that the deposition activates fibroblasts the cells that are responsible for creation of collagen and other elements of the extracellular matrix. […] The main risk factor for NSF in patients with severe renal impairment is exposure to GBCAs. […] Other factors include Acute renal damage, chronic kidney disease, and the number and length of exposures to GBCAs. […] The other significant risk factors are the type or kind of employed gadolinium chelate (non-ionic linear agents have a higher risk) and the administration of higher quantities of GBCAs. […] Renal dysfunction patients with chronic kidney disease (CKD) are most affected and the highest risk is those in stage 4 and 5. […] Acute Kidney Injury (AKI): Patients having contrast-enhanced imaging during or shortly after AKI experience are prone to NSF because acute kidney injury will slow down the clearance of gadolinium.

• #38 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mriquestions.com/what-is-nsf.html

  Nephrogenic systemic fibrosis (NSF) is a rare, progressive, often fatal disease characterized by skin thickening, painful joint contractures, and fibrosis of multiple organs including the lungs, liver, muscles, and heart. Nearly all documented cases have occurred in patients with chronic severe renal insufficiency who have received gadolinium contrast. The association between gadolinium and NSF was first reported by Danish nephrologists in 2006. Between 2006 and 2010 several hundred cases were diagnosed worldwide. […] NSF usually develops clinically within days to months following gadolinium exposure, although rare cases have been reported years later. Nearly all patients have been in various degrees of renal failure and many were on dialysis. Only exceedingly rare cases have been reported in patients with eGFRs 30 mL/min/1.73m. High and/or multiple doses of contrast are frequently reported, as are the use of linear contrast agents (ACR Group I). Other risk factors include liver disease and acidosis. Nephrogenic Systemic Fibrosis (NSF)

• #39 What Causes Nephrogenic Systemic Fibrosis? – The Rheumatologist

  https://www.the-rheumatologist.org/article/what-causes-nephrogenic-systemic-fibrosis/?singlepage=1

  Between 2003 and 2005, Thomas Grobner, MD, a nephrologist at the General Hospital of Wiener Neustadt, Austria, observed that five of nine patients receiving hemodialysis under his care developed skin changes of NSF within two to four weeks after undergoing magnetic resonance (MR) angiography with gadodiamide contrast. […] Shortly thereafter, Peter Marckmann, MD, of the department of nephrology, and colleagues from Copenhagen University Hospital at Herlev, Denmark, reported on 13 patients who also developed NSF following exposure to gadodiamide contrast during MR imaging. […] The strong association between NSF and prior exposure to gadolinium-containing contrast agents suggests that this condition might be prevented by not exposing patients with chronic kidney disease to gadolinium. […] Future studies should be directed toward understanding the molecular mechanism by which fibrosis occurs following gadolinium exposure in patients with underlying chronic kidney disease and targeting that mechanism with specific therapies that will prevent development of and reverse fibrosis.

• #40 Nephrogenic Systemic Fibrosis in Patients with Chronic Kidney Disease after the Use of Gadolinium-Based Contrast Agents: A Review for the Cardiovascular Imager

  https://www.mdpi.com/2075-4418/12/8/1816

  Since then, multiple cases with different presentations and histopathological findings have been published, and a scoring system to identify possible NSF cases was subsequently created. […] The presence of dermal hypercellularity, CD34+ cells, procollagen type I, thick and thin collagen bundles, and osseous metaplasia significantly point toward NSF diagnosis. […] As it was previously stated, when compared to L-GBCAs, M-GBCAs confer a significantly lower risk of NSF. […] There is not a specific prophylaxis regimen to prevent the onset of NSF. The current approach is based on minimizing the impact of predisposing risk factors and performing hemodialysis sessions right after GBCA exposure in patients with a history of ESRD on RRT. […] Even though the newer macrocyclic agents have proven to be much safer in patients with chronic kidney disease and end-stage renal failure, clinicians must fully understand the clinical characteristics and risk factors of this devastating pathology and maintain a high degree of suspicion to prevent and recognize it.

• #41 Nephrogenic systemic fibrosis: A frivolous entity

  https://www.wjgnet.com/2220-6124/full/v10/i3/29.htm

  NSF is a progressive, severely disabling fibrotic condition, which develops in patients with impaired kidney function exposed to GBCAs. However, the occurrence of NSF with newer contrast agents has been questioned in recent times. Determination of the putative underlying mechanisms, etiological or triggering factors necessitates further research and long-term data. Genetic predisposition may be a new revelation in future studies. Therapeutic approaches in the present literature are limited and have reduced benefit.

• #42 The extra miles on preventing nephrogenic systemic fibrosis – Kartamihardja – Quantitative Imaging in Medicine and Surgery

  https://qims.amegroups.org/article/view/31257/html

  This systemic review showed that the regulation for GBCA use in clinical practice, including screening of renal function, careful review on population at risk (i.e., pregnant women, or patients with confounding disease), and whether the patients requires multiple dose, can almost eliminated new cases of NSF.

• #43 Nephrogenic Systemic Fibrosis, Moh’d sharshir | PPT

  https://www.slideshare.net/slideshow/nephrogenic-systemic-fibrosis/101723380

  Among patients with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 or those on dialysis, recommend NOT administering gadolinium-containing contrast agents (Grade 1B), unless clinical conditions make gadolinium-based imaging absolutely necessary. […] There is no proven medical therapy for NSF other than recovery of renal function.

• #44 Nephrogenic systemic fibrosis (NSF) – Questions and Answers ​in MRI

  https://mri-q.com/what-is-nsf.html

  The strong association with renal insufficiency most likely relates to the prolonged biological half-life due to prolonged excretion of gadolinium. However, other factors have been imputed, including metabolic acidosis; elevated iron and phosphate levels; erythropoietin therapy; vasculopathy; and infectious/inflammatory mediators. […] The pathogenesis of NSF is believed to begin with the displacement of the Gd ion from its chelate by another metallic cation (Fe+3, Zn+2, or Ca+2) through a so-called transmetalation reaction: (Metal ion) + Gd-Chelate Metal-Chelate + Gd+3. The free Gd ion is then deposited in the skin and other soft tissues. There it is engulfed by CD163+ iron-recycling and other macrophages creating an inflammatory response and cytokine release. Circulating fibrocytes (immunologically unique CD-34 positive cells derived from bone marrow) deposit in tissue, transforming into spindle cells that proliferate and become the hallmark of the disease. Following recognition of this disorder and its association with gadolinium in patients with renal insufficiency, the worldwide radiology community responded immediately to put an end to this iatrogenic disease. Today, NSF has been nearly completely eliminated due to these measures. In more recent times, however, gadolinium-induced plaques have been reported in the extremities not meeting the full criteria for NSF. The story of NSF is sad one that we radiologists created. It should serve as a lesson that even drugs which appear to be extraordinarily safe may not be infinitely safe for all patients. Sometimes adverse effects may be subtle, disguised, or appear at long time intervals following administration. NSF is thus a call and reminder to be forever vigilant.

• #45 Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines

  https://consultqd.clevelandclinic.org/gadolinium-induced-nephrogenic-systemic-fibrosis-classification-risk-and-guidelines

  The guidelines set by the FDA and the radiology societies were undoubtedly effective in curbing the disease and eventually eliminating it. A recent review of 639 patients with biopsy-proven NSF from 173 articles estimated that the risk of NSF per million exposures had decreased from 2.07 before 2008 to 0.028 afterward. Most cases were associated with exposure to group I agents. […] Although NSF has been basically eradicated since the guidelines were implemented, several cases of NSF have been reported in patients who never were exposed to gadolinium. This suggests that gadolinium-based contrast agents are a major trigger for NSF, but they may not be the only one. Additionally, in recent years, there have been data suggesting that gadolinium can deposit in the brain after repeated exposure to gadolinium-based contrast agents, even in patients with healthy kidneys. The significance of this brain deposition remains unknown, and to date, no adverse health effects have been uncovered.

• #46 Nephrogenic systemic fibrosis: A frivolous entity

  https://www.wjgnet.com/2220-6124/full/v10/i3/29.htm

  NSF is a progressive, severely disabling fibrotic condition, which develops in patients with impaired kidney function exposed to GBCAs. However, the occurrence of NSF with newer contrast agents has been questioned in recent times. Determination of the putative underlying mechanisms, etiological or triggering factors necessitates further research and long-term data. Genetic predisposition may be a new revelation in future studies. Therapeutic approaches in the present literature are limited and have reduced benefit.

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