Fibroza układowa nefrogeniczna

Fibroza układowa nefrogeniczna
Epidemiologia

Fibroza układowa nefrogeniczna (NSF) to rzadka, potencjalnie śmiertelna choroba związana z ekspozycją na środki kontrastowe zawierające gadolin (GBCA) u pacjentów z zaawansowaną niewydolnością nerek, szczególnie przy eGFR <30 ml/min/1,73 m². Choroba objawia się włóknieniem skóry oraz głębszych tkanek, prowadząc do znacznej niepełnosprawności i ryzyka zgonu. Epidemiologicznie NSF dotyczy pacjentów w różnym wieku, najczęściej 51-60 lat, bez predyspozycji płciowej czy etnicznej. Ryzyko rozwoju NSF jest silnie związane z typem GBCA: środki liniowe (grupa I) niosą wysokie ryzyko (36,5/100 000 badań MRI), natomiast makrocykliczne (grupa II) i inne (grupa III) mają ryzyko <0,07%. Dodatkowe czynniki ryzyka to wysoka dawka i skumulowana ekspozycja, stan zapalny oraz hiperfosfatemia. Po wprowadzeniu ostrzeżeń FDA i EMA w 2007 roku oraz restrykcji stosowania GBCA u pacjentów z eGFR <30 ml/min/1,73 m² liczba nowych przypadków NSF drastycznie spadła, z ostatnim zgłoszonym przypadkiem w USA w 2010 roku.

Epidemiologia i występowanie fibrozy układowej nefrogenicznej

Rozpowszechnienie NSF na świecie
Czynniki demograficzne i rozpowszechnienie
Związek z czynnikami ryzyka
Związek z ekspozycją na środki kontrastowe zawierające gadolin
Częstotliwość występowania w zależności od typu GBCA
Czynniki wpływające na ryzyko NSF

Nadzór i monitorowanie NSF

Ograniczenie występowania po wprowadzeniu wytycznych
Aktualne wytyczne dotyczące nadzoru i profilaktyki NSF
Rola dializy w profilaktyce NSF
Problemy i wyzwania w monitorowaniu NSF

Znaczenie kliniczne i przeciwdziałanie NSF

Działania zapobiegawcze i wytyczne bezpieczeństwa
Przesiewowe badania funkcji nerek
Komunikacja ryzyka i świadomość kliniczna
Nowe trendy i kierunki w monitorowaniu NSF
Kolejne rozdziały

Epidemiologia i występowanie fibrozy układowej nefrogenicznej

Fibroza układowa nefrogeniczna (ang. Nephrogenic Systemic Fibrosis, NSF) to rzadka, potencjalnie śmiertelna choroba, rozpoznana po raz pierwszy w 1997 roku, a opisana w literaturze medycznej w 2000 roku.¹² Początkowo nazwana nefrogeniczną dermopathią włókniejącą (NFD) ze względu na charakterystyczne zmiany skórne, jednak późniejsze badania wykazały, że u niektórych pacjentów występuje również włóknienie głębszych struktur, w tym mięśni, powięzi, płuc i serca.³⁴

Rozpowszechnienie NSF na świecie

Według danych Amerykańskiej Agencji ds. Żywności i Leków (FDA), około 4,5 miliona Amerykanów jest rocznie narażonych na działanie środków kontrastowych zawierających gadolin (GBCA). Do 2019 roku FDA odnotowała 3094 przypadki NSF, w tym 742 zgonów i 2922 poważnych zachorowań.⁵ W 2019 i 2020 roku zgłoszono po 32 nowe przypadki NSF.⁶

Dania ma najwyższą odnotowaną częstość występowania NSF na świecie, wynoszącą 12 przypadków na milion mieszkańców. W badaniu przeprowadzonym w Danii znaleziono 65 pacjentów z NSF, co daje wskaźnik 65 na 5,6 miliona mieszkańców.⁷⁸⁹ Wysoki wskaźnik może wynikać z wysokiego poziomu świadomości choroby wśród lekarzy, polityków i mediów, a także faktu, że przeprowadzono ogólnokrajowe badanie dotyczące NSF.⁸

W Irlandii odnotowano jedynie trzy przypadki NSF wśród 1915 pacjentów dializowanych, co daje częstość występowania 0,002 wśród pacjentów z końcowym stadium choroby nerek.¹⁰ W publikacjach naukowych opisano łącznie mniej niż 500 przypadków NSF.¹¹

Czynniki demograficzne i rozpowszechnienie

Fibroza układowa nefrogeniczna dotyka w przybliżeniu równą liczbę mężczyzn i kobiet, bez związku z pochodzeniem etnicznym lub regionem geograficznym.¹²¹³ Choroba najczęściej występuje u osób w średnim wieku, ale opisano przypadki u pacjentów w różnym wieku – od dzieciństwa do starości.¹² Potwierdzone przypadki NSF zgłoszono u pacjentów w wieku od 8 do 87 lat, z najwyższą częstością występowania w przedziale wiekowym 51-60 lat.¹⁴

Badania epidemiologiczne sugerują, że występowanie NSF nie jest związane z płcią ani pochodzeniem etnicznym i nie uważa się, że ma podłoże genetyczne.¹² Większość przypadków NSF odnotowano w Stanach Zjednoczonych, następnie w Europie i Azji.¹⁵

Związek z czynnikami ryzyka

Najważniejszym czynnikiem ryzyka rozwoju NSF jest zaawansowana niewydolność nerek.¹⁶¹⁷ NSF występuje niemal wyłącznie u pacjentów z niewydolnością nerek, szczególnie u tych z szacunkowym współczynnikiem filtracji kłębuszkowej (eGFR) poniżej 30 ml/min/1,73m².¹⁸¹⁵

Według badania Zou i wsp., dwie najbardziej narażone grupy to pacjenci z przewlekłą niewydolnością nerek (CRF) poddawani dializie (85% przypadków) oraz pacjenci z ostrą niewydolnością nerek.¹⁹ Ryzyko jest największe wśród pacjentów z zaawansowaną przewlekłą chorobą nerek (CKD), szczególnie w stadium 4 i 5.²⁰

Chociaż NSF najczęściej występuje u pacjentów z zaawansowaną CKD i schyłkową niewydolnością nerek, opisano również rzadkie przypadki NSF u pacjentów z CKD w stadium 3a. W jednym z badań opisano pacjenta, u którego rozwinęła się NSF podczas CKD w stadium 3a, sześć miesięcy po pierwszej ekspozycji na gadolin.²⁰

Związek z ekspozycją na środki kontrastowe zawierające gadolin

Rozwój NSF jest silnie związany z ekspozycją na środki kontrastowe zawierające gadolin (GBCA) stosowane w obrazowaniu metodą rezonansu magnetycznego (MRI) u pacjentów z niewydolnością nerek.²¹¹⁴ Pierwsza sugestia związku między NSF a gadolinem pojawiła się w 2006 roku, gdy Grobner opisał rozwój objawów skórnych u 5 pacjentów z końcowym stadium choroby nerek 2-4 tygodnie po przeprowadzeniu angiografii rezonansu magnetycznego z kontrastem.²²²³

W badaniu kohortowym przeprowadzonym w Stanach Zjednoczonych w 2007 roku z udziałem pacjentów dializowanych wykazano 2,4% ryzyko rozwoju NSF po ekspozycji na środki kontrastowe zawierające gadolin o różnych formułach.²⁴ W przypadku pacjentów z eGFR poniżej 30 ml/min, każde badanie radiologiczne z użyciem gadolinu wiązało się z 2,4% ryzykiem rozwoju NSF.²

W analizie epidemiologicznej przeprowadzonej przez Thomsena i wsp. ryzyko rozwoju NSF u pacjentów z niewydolnością nerek po ekspozycji na GBCA zostało określone na nawet 25-30%.²⁵²⁶²⁷²⁸ Z kolei badanie przeprowadzone przez Deo i wsp. na populacji pacjentów ze schyłkową niewydolnością nerek wykazało częstość występowania NSF na poziomie 4,3 przypadków na 1000 pacjento-lat.²

Częstotliwość występowania w zależności od typu GBCA

Ryzyko rozwoju NSF znacząco różni się w zależności od zastosowanego typu środka kontrastowego zawierającego gadolin. Środki kontrastowe GBCA zostały sklasyfikowane na trzy grupy w zależności od ryzyka wywoływania NSF:²¹²⁹

Grupa I (wysokie ryzyko) – liniowe środki kontrastowe (np. gadodiamid, gadopentetan dimegluminy, gadowersetamid)
Grupa II (niskie ryzyko) – makrocykliczne środki kontrastowe (np. gadobutrol, gadoterate meglumina, gadoteridol)
Grupa III (bardzo niskie ryzyko) – pozostałe środki kontrastowe

²¹²⁰

Przy stosowaniu GBCA z grupy 1 (wysokiego ryzyka) szacowana częstość występowania wynosiła 36,5 przypadków na 100 000 badań MRI z użyciem kontrastu gadolinowego.⁵ Systematyczne przeglądy wykazały, że u pacjentów otrzymujących GBCA z grupy 2 lub 3 nie rozwinęła się potwierdzona biopsją NSF; szacowane ryzyko NSF przy stosowaniu GBCA z grupy 2 lub 3 jest mniejsze niż 0,07%.⁵³⁰

Czynniki wpływające na ryzyko NSF

Ryzyko rozwoju NSF zależy od kilku kluczowych czynników:⁵

Stopień resztkowej funkcji nerek
Rodzaj zastosowanego GBCA
Wielkość początkowej dawki GBCA
Skumulowana dawka GBCA

³¹

W jednym z badań analizujących częstość występowania NSF w dwóch dużych ośrodkach medycznych stwierdzono, że częstość NSF po podaniu wysokiej dawki GBCA wzrosła do 0,4% u pacjentów w programie przewlekłej hemodializy i do 8,8% u tych z eGFR poniżej 15 ml/min, którzy nie byli poddawani hemodializie.³²³³

Częstość NSF u pacjentów z ostrą niewydolnością nerek, którzy otrzymali wysoką dawkę, gdy ich poziom kreatyniny wzrastał, wynosiła 19% (11 z 58 pacjentów), gdy hemodializa była opóźniona o więcej niż 2 dni.³⁴ Zwiększone ryzyko NSF było również związane ze stanem zapalnym i hiperfosfatemią.³⁴

Nadzór i monitorowanie NSF

Ograniczenie występowania po wprowadzeniu wytycznych

Po zidentyfikowaniu GBCA jako przyczyny NSF w 2006 roku oraz wprowadzeniu środków kontrolnych i zapobiegawczych, liczba nowych przypadków NSF drastycznie się zmniejszyła.¹²¹⁶ W 2007 roku zarówno FDA, jak i Europejska Agencja Leków (EMA) wydały ostrzeżenia podkreślające ryzyko NSF związane z używaniem GBCA.²³

W odpowiedzi na to zagrożenie FDA nakazała umieszczenie tzw. „czarnej ramki ostrzegawczej” (black box warning) w oznakowaniu wszystkich GBCA, podkreślającej ryzyko NSF u pacjentów z ostrą/przewlekłą ciężką chorobą nerek (GFR < 30 ml/min/1,73 m²) lub ostrym uszkodzeniem nerek.³⁵⁶ Etykieta została zaktualizowana w 2010 roku i zawierała zalecenie przeprowadzania badań przesiewowych funkcji nerek, zmniejszenia dawki kontrastu i stosowania kontrastów o niższym ryzyku.⁶

Od 2008 roku liczba zgłoszonych przypadków NSF znacząco spadła, co może świadczyć o przestrzeganiu zaleceń dotyczących unikania GBCA u pacjentów z GFR poniżej 30 ml/min/1,73 m².⁶²¹ Ostatni zgłoszony przypadek w Stanach Zjednoczonych pochodzi z 2010 roku, a ostatni raport na świecie był w 2012 roku.³⁶

Wytyczne ustalone przez FDA i towarzystwa radiologiczne były niewątpliwie skuteczne w ograniczaniu choroby, a w końcu w jej eliminacji. Niedawny przegląd 639 pacjentów z potwierdzoną biopsją NSF z 173 artykułów oszacował, że ryzyko NSF na milion ekspozycji zmniejszyło się z 2,07 przed 2008 rokiem do 0,028 po nim.³⁶

Aktualne wytyczne dotyczące nadzoru i profilaktyki NSF

Obecne wytyczne opracowane przez organizacje radiologiczne i nefrologiczne zalecają następujące podejście do pacjentów z ryzykiem NSF:²¹²⁹³⁷

Przesiewowa ocena funkcji nerek przy użyciu instytucjonalnych kwestionariuszy przesiewowych i obliczenie eGFR
Unikanie stosowania GBCA z grupy I (wysokiego ryzyka) u pacjentów z ostrym uszkodzeniem nerek lub przewlekłą chorobą nerek
W przypadku pacjentów z zaawansowaną chorobą nerek preferowane jest stosowanie GBCA z grupy II (niskiego ryzyka)

²¹¹⁸

Amerykańskie Kolegium Radiologów (ACR) i Narodowa Fundacja Nerek wydały w listopadzie 2020 roku wspólne oświadczenie, w którym stwierdzono: „Ponieważ ryzyko włóknienia układowego nefrogenicznego jest tak niskie w przypadku środków kontrastowych zawierających gadolin z grupy II, potencjalne szkody wynikające z opóźniania lub wstrzymywania podawania GBCA z grupy II w klinicznie wskazanym badaniu MRI u pacjenta z ostrym uszkodzeniem nerek lub szacunkową szybkością filtracji kłębuszkowej mniejszą niż 30 ml/min/1,73 m² mogą przeważać nad ryzykiem NSF w większości sytuacji klinicznych, niezależnie od stanu dializy.”³⁸³⁷

W 2021 roku Komitet ACR ds. Leków i Środków Kontrastowych uznał, że ryzyko NSF wśród pacjentów, którym podano standardowe dawki GBCA z grupy II, jest „wystarczająco niskie lub potencjalnie nieistniejące, że ocena funkcji nerek za pomocą kwestionariusza lub badań laboratoryjnych jest opcjonalna przed dożylnym podaniem.”³⁸³⁷

Rola dializy w profilaktyce NSF

Rola dializy w zapobieganiu NSF nie jest do końca jasna. Obecnie przyjmuje się, że ryzyko rozwoju NSF może się zmniejszyć, gdy pacjenci są poddawani natychmiastowej dializie (< 24 godzin) po podaniu środka kontrastowego.⁶ Jednak Saitoh i wsp. zwrócili uwagę, że jeden zabieg dializacyjny nie jest wystarczający do usunięcia całego gadolinu.⁶

W badaniu dotyczącym częstości występowania NSF w dwóch dużych ośrodkach medycznych stwierdzono, że u pacjentów z eGFR poniżej 15 ml/min hemodializa pomogła zapobiec NSF.³⁴ Z drugiej strony, wskaźnik NSF u pacjentów z ostrą niewydolnością nerek, którzy otrzymali wysoką dawkę GBCA, wynosił aż 19%, gdy hemodializa była opóźniona o więcej niż 2 dni.³⁴

Problemy i wyzwania w monitorowaniu NSF

Dokładne określenie rzeczywistej liczby przypadków NSF stanowi wyzwanie z kilku powodów. Wszystkie dowody wskazują na to, że prawdziwa liczba pacjentów z NSF nie została dokładnie obliczona; choroba wydaje się być niedodiagnozowana z różnych przyczyn.¹

Częstość występowania przypadków NSF różni się w zależności od różnych GBCA, a odpowiednia dokumentacja przypadków NSF po ekspozycji na pozakomórkowe GBCA pozostaje problemem.¹ Ponadto, wiele osób jest narażonych na różne związki GBCA, co utrudnia oszacowanie wpływu pojedynczego GBCA.³¹

Model symulacyjny wykazał, że pacjenci otrzymujący GBCA o niższym udziale w rynku i późnym wprowadzeniu na rynek są mniej prawdopodobni do zaobserwowania w niezakłóconym środowisku. Rok wprowadzenia na rynek, a także udział w rynku USA w latach 2000-2007, znacznie wpłynęły na bezwzględną liczbę zgłoszeń NSF dla każdego GBCA, ich prawdopodobieństwo a priori wywołania NSF, a także ich prawdopodobieństwo a priori powiązania z niezakłóconymi przypadkami NSF.³⁹²²

Znaczenie kliniczne i przeciwdziałanie NSF

Znaczenie kliniczne NSF wynika z faktu, że jest to potencjalnie śmiertelna choroba, która może prowadzić do znacznej niepełnosprawności. Pacjenci z piorunującą postacią NSF mogą stać się zależni od wózka inwalidzkiego w ciągu kilku tygodni z powodu rozwoju przykurczów zgięciowych i utraty mobilności.¹³

Śmierć może nastąpić w wyniku powikłań choroby nerek lub zabiegu przeszczepienia, a także złamań i upadków wynikających z zależności od wózka inwalidzkiego.¹³ NSF jest poważną chorobą, która może prowadzić do znacznego upośledzenia funkcjonowania i jakości życia pacjentów.

Działania zapobiegawcze i wytyczne bezpieczeństwa

W celu zapobiegania NSF wprowadzono następujące działania i wytyczne:⁶²¹⁴⁰

Ograniczenie stosowania GBCA u pacjentów z zaburzeniami czynności nerek
Restrykcyjne stosowanie GBCA u pacjentów z CKD w stadium 4 lub 5
Unikanie stosowania gadodiamidu i gadopentetatu dimegluminy u pacjentów z niewydolnością nerek
Ostrożne stosowanie innych liniowych GBCA
Preferowanie GBCA z grupy II (niskiego ryzyka) u pacjentów z ryzykiem NSF
Stosowanie najniższej skutecznej dawki GBCA
Unikanie wielokrotnego podawania GBCA w krótkim czasie

²⁷²⁶²⁵

Od czasu wprowadzenia tych wytycznych liczba nowych przypadków NSF drastycznie spadła. Nie zgłoszono żadnych nowych przypadków NSF przez ponad 10 lat.¹⁶⁴¹ Jest to głównie wynikiem świadomości FDA i środowiska medycznego na temat wpływu GBCA na osoby z chorobami nerek.⁴¹

Przesiewowe badania funkcji nerek

Badania przesiewowe funkcji nerek są ważnym elementem zapobiegania NSF. Komitet ACR ds. Leków i Środków Kontrastowych uznał jednak, że ryzyko NSF związane ze standardowymi dawkami GBCA z grupy II jest na tyle niskie, że ocena funkcji nerek za pomocą kwestionariusza lub badań laboratoryjnych jest opcjonalna przed dożylnym podaniem.³⁸³⁷

GBCA z grupy II mogą być podawane pacjentom z grupy wysokiego ryzyka bez badań przesiewowych funkcji nerek i bez kontaktu z lekarzem kierującym, w zależności od indywidualnych wzorców praktyki.³⁸³⁷

Komunikacja ryzyka i świadomość kliniczna

Świadomość NSF wśród radiologów i nefrologów jest kluczowa dla skutecznego zapobiegania tej chorobie. W wyniku zwiększonej świadomości na temat choroby wśród radiologów i nefrologów częstość występowania NSF maleje.¹¹

Fibroza układowa nefrogeniczna nie jest chorobą z przeszłości, a FDA nadal otrzymuje raporty o nowych przypadkach NSF każdego roku za pośrednictwem systemu raportowania zdarzeń niepożądanych FDA.⁶ Dlatego ważne jest, aby lekarze zlecający badania MRI z użyciem GBCA byli świadomi ryzyka NSF.⁴²

Chociaż niektóre autorytety sugerują, że przypadki NSF nie występują po zastosowaniu nowszych środków kontrastowych zawierających gadolin, kompleksowa analiza sugeruje, że przypadki mogą występować sporadycznie. Ostrożne stosowanie gadolinu u pacjentów z poważnie ograniczoną funkcją nerek jest wskazane.⁴³

Nowe trendy i kierunki w monitorowaniu NSF

W ostatnich latach pojawiły się dane sugerujące, że gadolin może gromadzić się w mózgu po wielokrotnej ekspozycji na GBCA, nawet u pacjentów ze zdrowymi nerkami. Znaczenie tego odkładania się w mózgu pozostaje nieznane, a do tej pory nie wykryto niekorzystnych skutków zdrowotnych.⁴⁴

Chociaż NSF została zasadniczo wyeliminowana od czasu wdrożenia wytycznych, zgłoszono kilka przypadków NSF u pacjentów, którzy nigdy nie byli narażeni na gadolin. Sugeruje to, że środki kontrastowe zawierające gadolin są głównym czynnikiem wyzwalającym NSF, ale mogą nie być jedynym.⁴⁴

Nowsze wytyczne i raporty pokazują, że nie wszystkie środki kontrastowe wiążą się z takim samym ryzykiem wywołania NSF. Środki kontrastowe o najniższym ryzyku to: gadobenat dimegluminy, gadoteridol, gadoterydol meglumin i gadobutrol.⁶

Meta-analiza i systematyczny przegląd ryzyka NSF u pacjentów z przewlekłą chorobą nerek w stadium 4 lub 5 otrzymujących GBCA z grupy II, przeprowadzona przez Woolena i wsp., wykazały, że zastosowanie kontrastów o najniższym ryzyku u pacjentów z chorobą nerek w stadium 4 i 5 CKD wiąże się z ryzykiem mniejszym niż 0,07%.⁶³⁰

Poza ryzykiem związanym z rodzajem GBCA, istotnym czynnikiem jest również dawka i częstotliwość podawania. Jak wykazano w jednym z badań, częstość występowania NSF po zastosowaniu GBCA bez badań przesiewowych funkcji nerek wynosiła zero z 74 124 pacjentów otrzymujących standardową dawkę GBCA i 15 (0,17%) z 8997 pacjentów otrzymujących wysoką dawkę (P < 0,001).³³

Oprócz oceny funkcji nerek i rodzaju GBCA, ważne jest również monitorowanie innych czynników ryzyka, takich jak stan zapalny, hiperfosfatemia i kwasica metaboliczna, które mogą zwiększać ryzyko NSF u pacjentów z niewydolnością nerek.⁴⁵

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Materiały źródłowe

#1 Nephrogenic Systemic Fibrosis: History and Epidemiology
https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2060118109
Nephrogenic systemic fibrosis (NSF) is a new disease; the first case was diagnosed in 1997. […] It took 9 years before an association between NSF and gadolinium-based contrast agents (Gd-CAs) was identified. […] The prevalence of NSF cases varies between the various Gd-CAs, and adequate documentation of NSF cases after exposure to extracellular Gd-CAs remains a problem. […] All evidence points toward the fact that the real number of patients who have NSF has not been accurately totaled; the disease seems to be underdiagnosed for various reasons.
#2 Nephrogenic Systemic Fibrosis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1097889-overview
Nephrogenic systemic fibrosis is an uncommon condition. Since 1997, hundreds of cases have been reported to the NFD Registry. Few cases have occurred since guidelines have been instituted by the ACR, FDA, and EU regulatory authorities; however, this author has heard at meetings that a few sporadic cases have occurred. […] Deo et al studied a population of patients with end-stage renal disease in and around Bridgeport, Connecticut over an 18-month period. The incidence of nephrogenic systemic fibrosis was 4.3 cases per 1000 patient-years. Each radiologic study using gadolinium presented a 2.4% risk for developing nephrogenic systemic fibrosis. […] Nephrogenic systemic fibrosis is an uncommon condition. Several case series from Europe have been reported. Four cases were described in a report in the British Journal of Dermatology in March 2003. Additional cases have been reported in Germany and Switzerland.
#3 Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease – UpToDate
https://www.uptodate.com/contents/nephrogenic-systemic-fibrosis-nephrogenic-fibrosing-dermopathy-in-advanced-kidney-disease
Nephrogenic systemic fibrosis (NSF) is a disorder seen only in patients with advanced kidney disease and is characterized by two primary features: Thickening and hardening of the skin overlying the extremities and trunk; Marked expansion and fibrosis of the dermis in association with CD34+ fibrocytes. […] NSF was originally named nephrogenic fibrosing dermopathy (NFD) because of the characteristic skin findings. However, subsequent studies showed that some patients had fibrosis of deeper structures, including muscle, fascia, lungs, and heart. […] While NSF is only seen among patients with kidney disease, retention of gadolinium (Gd) has been demonstrated in other organs (eg, brain) in patients without and with kidney disease.
#4 Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease – UpToDate
https://www.uptodate.com/contents/nephrogenic-systemic-fibrosis-nephrogenic-fibrosing-dermopathy-in-advanced-kidney-disease/print
Nephrogenic systemic fibrosis (NSF) is a disorder seen only in patients with advanced kidney disease and is characterized by two primary features: […] NSF was originally named nephrogenic fibrosing dermopathy (NFD) because of the characteristic skin findings. However, subsequent studies showed that some patients had fibrosis of deeper structures, including muscle, fascia, lungs, and heart. […] While NSF is only seen among patients with kidney disease, retention of gadolinium (Gd) has been demonstrated in other organs (eg, brain) in patients without and with kidney disease.
#5 Nephrogenic Systemic Fibrosis – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK567754/
Nephrogenic systemic fibrosis is an iatrogenic disease first identified in 2000. According to a report by the FDA, about 4.5 million Americans are exposed to GBCAs annually. Until 2019, the FDA reported 3094 cases of NSF, including 742 deaths and 2922 serious cases. Of note, the US has the second-highest MRI utilization rate after Germany. As noted above, 32 cases were reported in each of 2019 and 2020. […] NSF affects any ethnicity, sex, or age. The risk of developing NSF depends on the amount of residual renal function and the type of GBCA used. The amount of the initial dose and the cumulative dose of GBCA can also increase the risk. When the high-risk group 1 GBCAs were used, the estimated incidence was 36.5 cases per 100,000 gadolinium-enhanced MRI examinations. Systematic reviews have found that no patients developed biopsy-proven NSF among patients receiving group 2 or 3 GBCAs; the estimated risk of NSF when using group 2 or 3 GBCAs is less than 0.07%.
#6 Nephrogenic Systemic Fibrosis as a Complication after Gadolinium-Containing Contrast Agents: A Rapid Review
https://www.mdpi.com/1660-4601/18/6/3000
Nephrogenic systemic fibrosis (NFS) is a generalized disorder occurring in people with kidney failure. This new disease entity can lead to significant disability or even death. Gadolinium-associated systemic fibrosis is related to exposure to contrast agents used for magnetic resonance imaging. The aim of this study was to review the literature in available scientific databases on NFSâcomplication after gadolinium-containing contrast agents. Since 2008, the number of reported cases of NSF has decreased significantly. More recent guidelines and reports indicate that not all contrast agents are associated with the same risk of developing NSF. Most NSF occurs after exposure to linear contrast agents. Therefore, it is recommended to limit their use, especially in dialyzed patients and patients with a GFR < 30 mL/min. 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. The common feature of all patients with NSF is renal failure. Many authors emphasized that the highest risk of NSF exists in patients with a GFR < 15 mL/min/1.73 mÂ² (i.e., chronic kidney disease at stage 5). The role of dialysis in preventing NSF is unclear. Currently, it is assumed that the risk of developing NSF may decrease when patients undergo immediate dialysis (<24 h) after contrast medium administration. However, Saitoh et al., pointed out that one dialysis treatment is not sufficient to remove all gadolinium. In 2007, the US Food and Drug Administration (FDA) mandated a black box warning advising the avoidance of all gadolinium-containing contrast agents in at-risk patients. The label was updated in 2010. It included a recommendation to perform the screening of renal function tests, reduce the dose of contrast and use lower-risk contrasts. Implementation of the recommendations and changes in hospital policy have contributed to virtually eliminating this complication. Since 2008, the number of reported NSF cases has decreased significantly. This may show the adherence to regulatory recommendations to avoid GBCAs in patients with a GFR less than 30 mL/min/1.73 mÂ². More recent guidelines and reports show that not all contrast agents have the same risk of triggering NFS. The lowest risk contrast agents are: gadobenate dimeglumine, gadoteridol, gadoterate meglumine and gadobutrol. A systematic review and meta-analysis risk of NFS in Patients with Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent by Woolen et al., showed that the use of contrasts with the lowest risk in patients with kidney disease in stage 4 and 5 CKD is less than 0.07%. The risk of developing NSF is almost as small as the risk of developing an allergic reaction after contrast application, with frequencies varying from 0.004% to 0.7%. NSF is not an entity of the past, and the FDA continues to receive reports on new cases of NFS each year through the US Food and Drug Administration Adverse Reporting System Public Dashboard. There were 32 cases each reported in 2019 and 2020.
#7 Nephrogenic Systemic Fibrosis: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1097889-overview
A study in Denmark found a rate of 12 cases of nephrogenic systemic fibrosis per million, which may be the highest prevalence worldwide. […] In France, after new guidelines for use of gadolinium were instituted, a study of patients from 2009-2011 found that no cases of nephrogenic systemic fibrosis occurred.
#8 Nephrogenic Systemic Fibrosis in Denmarkâ A Nationwide Investigation | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082037
Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal impairment. […] The outcome of the nationwide investigation revealed that Denmark had 65 patients with nephrogenic systemic fibrosis and thereby the highest prevalence of nephrogenic systemic fibrosis worldwide with 65 per 5.6 million inhabitants, or 12 per million. […] The nationwide investigation in Denmark revealed the highest prevalence of NSF worldwide. This may be rooted in a high level of awareness of NSF both among doctors, politicians and, not least, the media, combined with the fact that a nationwide NSF investigation was initiated.
#9 Nephrogenic Systemic Fibrosis in Denmarkâ A Nationwide Investigation | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082037
This first nationwide NSF investigation showed a prevalence of 65 per 5.6 million inhabitants, or 12 per million in Denmark. To our knowledge, Denmark has the highest prevalence of NSF worldwide. […] The rise in the number of reported NSF cases and subsequent pressure from the media made a nationwide investigation mandatory in Denmark.
#10 Nephrogenic systemic fibrosis.
https://lenus.ie/handle/10147/114790
Nephroaenic systemic fibrosis (NSF) is a potentially fatal dermatological condition found exclusively in patients with advanced renal failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland’s experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients–giving a point prevalence among Irish end-stage kidney disease patients of 0.002. […] Caution with gadolinium administration must be exercised in patients with advanced renal failure.
#11 SciELO Brazil – Nephrogenic systemic fibrosis: concepts and perspectives Nephrogenic systemic fibrosis: concepts and perspectives
https://www.scielo.br/j/abd/a/YRrkNwbg8vdYmP5SR85wmcG/?lang=en
Nephrogenic systemic fibrosis is a chronic, progressive condition that develops in some patients with renal impairment after exposure to gadolinium-based contrast agents used in magnetic resonance imaging. […] The diagnosis of the disease requires careful clinicopathological correlation. […] Reduction and prevention of nephrogenic systemic fibrosis cases are based on limiting the use of gadolinium-based contrast agents in patients with kidney disorders (especially in patients with advanced renal failure at stages 4 and 5), and restricting their use to situations in which they are essential to diagnosis/follow-up. […] Due to increased awareness about the disease among radiologists and nephrologists, the incidence of nephrogenic systemic fibrosis is declining. […] NSF is a rare condition, with fewer than 500 cases reported in the literature.
#12 Nephrogenic systemic fibrosis – Wikipedia
https://en.wikipedia.org/wiki/Nephrogenic_systemic_fibrosis
Nephrogenic systemic fibrosis 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. […] 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. […] Screening for impaired kidney function is routinely conducted and has drastically reduced the incidence of NSF.
#13 SSA – POMS: DI 23022.835 – Nephrogenic Systemic Fibrosis – 10/06/2023
https://secure.ssa.gov/apps10/poms.nsf/lnx/0423022835
Nephrogenic Systemic Fibrosis (NSF) is a rare disease involving severe thickening and hardening of the skin (fibrosis) overlying the extremities and trunk. The cause of nephrogenic systemic fibrosis is attributed to 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 3, 4 and 5) and acute or chronic inflammatory insults. […] NSF affects males and females in approximately equal numbers. NSF may occur in children but most commonly affects the middle-aged. […] NSF is a debilitating and sometimes fatal disease. People with a fulminant (disease developing or progressing suddenly) form of NSF may become wheelchair dependent within weeks due to development of flexion contractures and loss of mobility. Death may result from complications of kidney disease or transplant surgery. In addition, fractures and falls from wheelchair dependency may be fatal.
#14
https://link.springer.com/article/10.1007/s00467-013-2636-z
Nephrogenic systemic fibrosis (NSF) is a multisystem disease seen exclusively in patients with renal impairment. […] There is a strong association with gadolinium-based contrast agents used in magnetic resonance imaging (MRI). […] After implementation of guidelines restricting the use of gadolinium-based contrast agents in at-risk patients, there has been a sharp reduction in new cases and no new reports in children. […] The occurrence of NSF following gadolinium (Gd)-based contrast-agent administration was first reported in 2006. […] NSF has been reported in approximately 500 patients worldwide, but in dialysis patients given high doses of Gd, the incidence is as high as 18 %. […] The natural history of NSF is variable. […] Confirmed cases of NSF have been reported in patients from 8 years to 87 years old, with a peak incidence at ages 51-60 years.
#15 Contrast Agent Safety and Nephrogenic Systemic Fibrosis | Radiology Key
https://radiologykey.com/contrast-agent-safety-and-nephrogenic-systemic-fibrosis/
Nephrogenic systemic fibrosis (NSF) is a rare disease typically found among individuals with severe renal impairment. […] NSF affects men and women equally and cases have been reported in Caucasian, African, Asian, Indian, and Hispanic individuals. Most cases have been identified in the United States, followed by Europe and Asia. […] There is a strong connection between NSF and poor renal function. […] One study looking at NSF incidence among patients receiving gadolinium contrast at two large medical centers in the United States found that all patients developing NSF had an estimated glomerular filtration rate (GFR) less than 30 mL/min/1.73 m2. […] The incidence of NSF associated with high-dose gadolinium increased from 0.4% among patients getting chronic hemodialysis to 8.8% among patients with a GFR less than 15 mL/min/1.73 m2 but who were not on hemodialysis.
#16 Nephrogenic Systemic Fibrosis (NSF): Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/17783-nephrogenic-systemic-fibrosis-nsf
Nephrogenic systemic fibrosis (NSF) is a rare disease that occurs mostly in people with kidney disease after exposure to gadolinium-based contrast agents (GBCAs). […] Its an incredibly rare disease. There havent been any new cases of NSF in over 10 years. The prevalence went down significantly after 2006 when the healthcare community became aware of how GBCAs affect people with kidney issues. […] There havent been any new reports of NSF in almost 15 years. This is due to the development and use of more stable, less toxic GBCAs. Limiting the use of gadolinium in people with kidney disease also played a role. The FDA advises against using older GBCAs in people with kidney disease or a kidney injury. […] The main risk factor for developing NSF is having kidney disease or some other kidney function impairment.
#17
https://step2.medbullets.com/renal/121624/gadolinium-associated-nephrogenic-systemic-fibrosis
Epidemiology […] Incidence […] rare […] […] […] Demographics […] occurs only in patients with renal failure […] […] […] Risk factors […] renal failure […] renal transplant […] chronic kidney disease […] exposure to gadolinium-containing agents
#18 Nephrogenic systemic fibrosis – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/nephrogenic-systemic-fibrosis/symptoms-causes/syc-20352299
Nephrogenic systemic fibrosis is a rare disease that occurs mainly in people with advanced kidney failure with or without dialysis. […] For some people with advanced kidney disease, being exposed to older gadolinium-based contrast agents (group 1) during magnetic resonance imaging (MRI) and other imaging studies has been identified as a trigger for development of this disease. Recognition of this link has dramatically reduced the incidence of nephrogenic systemic fibrosis. […] The Food and Drug Administration (FDA) recommends avoiding older gadolinium-based contrast agents (group 1) in people with acute kidney injury or chronic kidney disease. […] Avoidance of older gadolinium-based contrast agents (group 1) is key to preventing nephrogenic systemic fibrosis, as newer gadolinium-based contrast agents (group 2) are safer and are not associated with increased risk.
#19 Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media | NefrologÃa
https://revistanefrologia.com/en-renal-function-nephrogenic-systemic-fibrosis-articulo-X2013251414054390
Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. […] NSF affects most cases of patients with impaired renal function, particularly those with an estimated glomerular filtration rate of less than 30ml/min/1.73m2 independently of the origin of renal damage (acute, chronic or haemodialysis patients) who are administered GBCM. […] According to Zou et al., the two most affected groups are patients with chronic renal failure (CRF) on dialysis (85% of cases) and those with acute renal failure. […] Although various authors have reported different prevalences in accordance with the population selected, it is currently estimated that there is a mean incidence of 0%-18% in the risk population. […] Thanks to the knowledge of risk factors and the better use of GBCM, the number of cases of NSF has decreased significantly. […] Since 2008, there have been no cases of any CM being reported without these CM being replaced.
#20 :: JKMS :: Journal of Korean Medical Science
https://jkms.org/DOIx.php?id=10.3346/jkms.2020.35.e293
Nephrogenic systemic fibrosis (NSF) is a progressive systemic fibrosing disease that may occur after gadolinium contrast exposure. […] NSF is highly prevalent among patients with advanced chronic kidney disease (CKD). […] Although the development of NSF varies according to kidney function, the type and dose of GBCAs, NSF mainly occurs in patients with advanced chronic kidney disease (CKD), especially CKD stages 4 and 5. […] Only a few cases of NSF have been reported in patients with stage 3 CKD. […] This is the first reported case of NSF occurring in a stage 3a CKD patient without previous known risk factor. […] NSF mostly occurs in patients with advanced CKD and end stage renal disease. […] These patients have a 1%7% chance of developing NSF after exposure to GBCAs, especially type 1 GBCAs that contain linear ligands (such as gadodiamide, gadopentetate, and gadoversetamide). […] In conclusion, we described a patient who developed NSF during stage 3a CKD six months after first exposure to gadolinium.
#21 Nephrogenic systemic fibrosis | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/nephrogenic-systemic-fibrosis?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. […] The number of reported cases of NSF has significantly decreased since 2008, likely secondary to regulatory actions, reduced administration of group I GBCAs, and changes in clinical practice guidelines. […] Patients should be screened for the possible risk of developing nephrogenic systemic fibrosis (NSF) by using institutional screening questionnaires and calculating the eGFR. […] New consensus suggests that kidney function screening is optional for the use of group II GBCAs. […] The 2021 ACR Committee on Drugs and Contrast Media considers the risk of NSF among patients administered standard doses of group II GBCAs „sufficiently low or possibly nonexistent such that assessment of renal function with a questionnaire or laboratory testing is optional prior to intravenous administration.”
#22
https://journals.lww.com/investigativeradiology/fulltext/2018/09000/10_years_of_nephrogenic_systemic_fibrosis__a.5.aspx
Nephrogenic systemic fibrosis (NSF) was first described by Cowper et al in 2000, when they reported on 15 renal dialysis patients dating back to 1997 who had developed a scleromyxedema-like condition characterized by thickening and hardening of the skin of the extremities. […] The first link between NSF and gadolinium-based contrast agents (GBCAs) was suggested in 2006, when Grobner noted the development of skin symptoms in 5 patients with end-stage renal disease 2 to 4 weeks after they underwent contrast-enhanced magnetic resonance angiography with Omniscan. […] The European Medicines Agency (EMA) and the European Society of Urogenital Radiology defined risk categories for GBCAs with regard to NSF, classifying the macrocyclic GBCAs Gadovist, Dotarem, and ProHance as having the lowest risk for NSF development.
#23 Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines
https://consultqd.clevelandclinic.org/gadolinium-induced-nephrogenic-systemic-fibrosis-classification-risk-and-guidelines
Nephrogenic systemic fibrosis (NSF) is a debilitating and often-fatal fibrosing disease characterized by skin thickening and organ fibrosis. It was first reported in 15 dialysis patients in San Diego in the year 2000. However, the relationship between NSF and the use of gadolinium as contrast during MRI remained obscure for a long time, finally being suggested six years later in Europe. […] 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.
#24 SciELO Brazil – Nephrogenic systemic fibrosis: concepts and perspectives Nephrogenic systemic fibrosis: concepts and perspectives
https://www.scielo.br/j/abd/a/YRrkNwbg8vdYmP5SR85wmcG/?lang=en
A cohort study developed in the United States of America in 2007 with patients on dialysis showed a 2.4% risk of developing the disease after exposure to gadolinium-based contrast media of different formulations. […] The disease was described after the introduction of GBCA in high concentrations to perform magnetic resonance angiography in 1997 and after its use in a significant number of patients with renal impairment.
#25
https://journals.lww.com/co-nephrolhypertens/Fulltext/2008/05000/Nephrogenic_systemic_fibrosis__epidemiology_update.13.aspx?generateEpub=Article%7Cco-nephrolhypertens:2008:05000:00013%7C%7C
The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. […] Epidemiological and histochemical studies demonstrated that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. […] Up to 2530% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. […] It is mandatory to avoid exposing patients with renal failure to gadodiamide and gadopentetate dimeglumine. Other linear gadolinium-based contrast agents should be used with great caution.
#26 Nephrogenic systemic fibrosis: epidemiology update | CoLab
https://colab.ws/articles/10.1097%2FMNH.0b013e3282f4b605
Epidemiological and histochemical studies demonstrated that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. […] Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. […] It is mandatory to avoid exposing patients with renal failure to gadodiamide and gadopentetate dimeglumine. Other linear gadolinium-based contrast agents should be used with great caution.
#27 Nephrogenic systemic fibrosis: epidemiology update Â· ç é£ivySCI
https://www.ivysci.com/articles/5892353__Nephrogenic_systemic_fibrosis_epidemiology_update
Nephrogenic systemic fibrosis: epidemiology update […] Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. […] Epidemiological and histochemical studies demonstrated that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. […] Up to 2530% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. […] It is mandatory to avoid exposing patients with renal failure to gadodiamide and gadopentetate dimeglumine. Other linear gadolinium-based contrast agents should be used with great caution.
#28 Nephrogenic systemic fibrosis: epidemiology update
https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W1978351522
Nephrogenic systemic fibrosis: epidemiology update […] Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. […] Recent findings Epidemiological and histochemical studies demonstrated that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. […] Up to 2530% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. […] It is mandatory to avoid exposing patients with renal failure to gadodiamide and gadopentetate dimeglumine. Other linear gadolinium-based contrast agents should be used with great caution.
#29 Nephrogenic systemic fibrosis | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/nephrogenic-systemic-fibrosis?embed_domain=external.radpair.com%252525252527%25252525255b0%25252525255dfavicon.icoradiopaedia-icon-144.pngfavicon.icofavicon.icofavicon.ico&lang=gb
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. […] The number of reported cases of NSF has significantly decreased since 2008, likely secondary to regulatory actions, reduced administration of group I GBCAs, and changes in clinical practice guidelines. […] Patients should be screened for the possible risk of developing nephrogenic systemic fibrosis (NSF) by using institutional screening questionnaires and calculating the eGFR. […] New consensus suggests that kidney function screening is optional for the use of group II GBCAs. […] Recommendations pertaining to the administration of gadolinium-based contrast agents (GBCAs) in patients with kidney disease were updated in 2021, specifically with regard to the three different groups of GBCAs.
#30 #VisualAbstract: Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent | 2 Minute Medicine
https://www.2minutemedicine.com/visualabstract-risk-of-nephrogenic-systemic-fibrosis-in-patients-with-stage-4-or-5-chronic-kidney-disease-receiving-a-group-ii-gadolinium-based-contrast-agent/
1. In a systematic review and meta-analysis of the use of group II (low risk) gadolinium-based contrast agents (GBCA) for MRI in patients with stage 4 and 5 chronic kidney disease (CKD), there were no reported cases of nephrogenic systemic fibrosis (NSF). […] The current study is a systematic review and meta-analysis which evaluated the incidence and risk of NSF in patients with stage 4 and 5 CKD receiving group II GBCA. […] The study found that in a pooled sample of 4931 patients there was no reported cases of NSF and the upper 95% confidence interval limit for incidence was 0.07%. […] The main strengths of the meta-analysis include the large sample size, and low estimated bias in most domains. The main limitations of the study include the reliance on predominantly retrospective data with unblinded assessments, and the lack of universal standard for the diagnosis of NSF.
#31
https://link.springer.com/article/10.1007/s40134-014-0064-x
In addition to the aforementioned risk factors, higher one-time and cumulative doses of GBCA are considered additional risk factors for the development of NSF. […] Many patients who developed NSF after administration of GBCAs were exposed to different GBCA compounds, thus making it difficult to estimate the effects of an individual GBCA. […] Up to now (as of 5/2014), the number of unconfounded NSF cases that have been histologically confirmed is fewer than 1,000. […] The resulting calculated risk for NSF, accounting for the number of GBCA administrations worldwide, is thus on the order of 0.110 NSF cases per one million GBCA administrations in the general population depending on the GBCA. […] In a recently published study on the nationwide prevalence of NSF in Denmark, a prevalence of 12 cases per one million inhabitants was found. […] So far, this represents the highest reported prevalence worldwide, which according to the authors of the study could be explained by the high awareness of NSF in Denmark together with the initiation of this nationwide investigation.
#32 Incidence of nephrogenic systemic fibrosis at two large medical centers.
https://vivo.weill.cornell.edu/display/pubid18710976
PURPOSE: To determine the incidence and associated risk factors of nephrogenic systemic fibrosis (NSF) in patients who undergo gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance (MR) imaging. […] The incidence of NSF was calculated for patients who received a standard dose of GBCA, patients who received a high dose, and subgroups of patients with renal impairment. […] Fifteen patients developed NSF after gadolinium-enhanced MR imaging. All of them had an estimated glomerular filtration rate (eGFR) lower than 30 mL/min, and 11 had acute renal failure or acute deterioration of chronic renal failure. The incidence of NSF after gadolinium-enhanced MR imaging without screening for renal function was zero of 74,124 patients with the standard dose of GBCA and 15 (0.17%) of 8997 patients with the high dose.
#33 Incidence of nephrogenic systemic fibrosis at two large medical centers. | Pathology & Laboratory Medicine
https://pathology.weill.cornell.edu/research/publications/incidence-nephrogenic-systemic-fibrosis-two-large-medical-centers
PURPOSE: To determine the incidence and associated risk factors of nephrogenic systemic fibrosis (NSF) in patients who undergo gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance (MR) imaging. […] RESULTS: Fifteen patients developed NSF after gadolinium-enhanced MR imaging. All of them had an estimated glomerular filtration rate (eGFR) lower than 30 mL/min, and 11 had acute renal failure or acute deterioration of chronic renal failure. […] The incidence of NSF after gadolinium-enhanced MR imaging without screening for renal function was zero of 74,124 patients with the standard dose of GBCA and 15 (0.17%) of 8997 patients with the high dose (P .001). […] The NSF incidence associated with a high dose of GBCA increased to 0.4% in patients in a chronic hemodialysis program and to 8.8% in those who had an eGFR lower than 15 mL/min but were not undergoing hemodialysis (P .001).
#34 Incidence of nephrogenic systemic fibrosis at two large medical centers. | Pathology & Laboratory Medicine
https://pathology.weill.cornell.edu/research/publications/incidence-nephrogenic-systemic-fibrosis-two-large-medical-centers
The NSF incidence in the patients with acute renal failure who received a high dose when their creatinine level was increasing was 19% (11 of 58 patients) when hemodialysis was delayed for longer than 2 days. […] CONCLUSION: For patients with an eGFR lower than 15 mL/min, hemodialysis helped to prevent NSF. For patients with an eGFR lower than 30 mL/min who received a high dose of GBCA, acute renal failure, delayed hemodialysis after contrast agent injection, proinflammatory events, and hyperphosphatemia were associated with increased risk of NSF.
#35
https://journals.lww.com/investigativeradiology/fulltext/2018/09000/10_years_of_nephrogenic_systemic_fibrosis__a.5.aspx
In May 2007, the Food and Drug Administration (FDA) issued a boxed warning in the product labeling of all GBCAs, highlighting the risk of NSF in patients with acute/chronic severe kidney disease (GFR 30 mL/min/1.73 m2) or acute kidney injury. […] The goal of this analysis was to incorporate less widely discussed aspects for NSF risk assessment, such as the year of market introduction and the market share of the GBCAs. […] Nephrogenic systemic fibrosis occurs almost exclusively in multimorbid patients who received multiple doses of GBCAs spread over numerous magnetic resonance imaging (MRI) examinations. […] This analysis demonstrates the limitations of relying on case reports, particularly single-agent reports, when assessing the risk of NSF associated with any GBCA.
#36 Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines
https://consultqd.clevelandclinic.org/gadolinium-induced-nephrogenic-systemic-fibrosis-classification-risk-and-guidelines
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. […] 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. However, those guidelines were applied to all gadolinium-based contrast agents without considering their stability or association with NSF. […] On the basis of accumulating evidence, the recent guidelines of the American College of Radiology, the European Society of Urogenital Radiology, and the Canadian Association of Radiologists all permit the use of group II gadolinium-based contrast agents in patients with advanced kidney disease.
#37 Nephrogenic systemic fibrosis | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/nephrogenic-systemic-fibrosis?embed_domain=external.radpair.com%252525252527%25252525255b0%25252525255dfavicon.icoradiopaedia-icon-144.pngfavicon.icofavicon.icofavicon.ico&lang=gb
The 2021 ACR Committee on Drugs and Contrast Media considers the risk of NSF among patients administered standard doses of group II GBCAs „sufficiently low or possibly nonexistent such that assessment of renal function with a questionnaire or laboratory testing is optional prior to intravenous administration.” […] Group II GBCAs may be administered to high-risk patients without kidney function screening and without contact with the referring provider, depending on individual practice patterns. […] Joint consensus statements by the American College of Radiology (ACR) and the National Kidney Foundation were issued in November 2020 that stated: „Since the risk of nephrogenic systemic fibrosis is so low with group II gadolinium-based contrast [agents] (GBCAs), the potential harms of delaying or withholding group II GBCAs for a clinically indicated MRI in a patient with acute kidney injury or estimated glomerular filtration rate less than 30 mL/min/1.73 m2 may outweigh the risk of NSF in most clinical situations, regardless of dialysis status.”
#38 Nephrogenic systemic fibrosis | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/nephrogenic-systemic-fibrosis?lang=us
Group II GBCAs may be administered to high-risk patients without kidney function screening and without contact with the referring provider, depending on individual practice patterns. […] Joint consensus statements by the American College of Radiology (ACR) and the National Kidney Foundation were issued in November 2020 that stated: „Since the risk of nephrogenic systemic fibrosis is so low with group II gadolinium-based contrast [agents] (GBCAs), the potential harms of delaying or withholding group II GBCAs for a clinically indicated MRI in a patient with acute kidney injury or estimated glomerular filtration rate less than 30 mL/min/1.73 m2 may outweigh the risk of NSF in most clinical situations, regardless of dialysis status.” […] The risk estimate of NSF for group II GBCAs in patients with stage 5 chronic kidney disease is based on data from 2581 individuals. It is possible that NSF may rarely occur in this population.
#39
https://journals.lww.com/investigativeradiology/fulltext/2018/09000/10_years_of_nephrogenic_systemic_fibrosis__a.5.aspx
The aim of this study was to critically assess the evaluation and categorization process for nephrogenic systemic fibrosis (NSF) based on reports received by Bayer from 2006 to 2016. […] A total of 779 NSF reports received by Bayer globally from 2006 to 2016 were included in the analysis. […] Most of all reports (86%) originated from the United States. […] The simulation model demonstrated that patients receiving a GBCA with lower market share and late market introduction are less likely to be observed in an unconfounded setting. […] Year of market introduction, as well as US market share in 2000 to 2007, greatly influenced the absolute number of NSF reports for each GBCA, their a priori probability to cause NSF, as well as their a priori probability to be associated with unconfounded cases of NSF.
#40
https://link.springer.com/article/10.1007/s00467-013-2636-z
The conclusion drawn in the European and American guidelines is that patients most at risk of NSF are those with CKD stage 4 or 5, including those needing dialysis and those with reduced renal function who have or are awaiting liver transplantation. […] Taking sales figures as a surrogate for quantities of Gd prescribed, there has been a decrease in worldwide sales of gadodiamide (the agent most frequently associated with NSF) since 2007 against a backdrop of increasing sales prior to this period. […] Since 2007, there has been a dramatic drop in the number of NSF cases reported, with multiple large studies in Sweden and the USA identifying reduced incidence or no new cases of NSF following restrictive prescribing policies. […] Although evidence in children is scant, current guidelines extrapolate from adult data and urge extra caution in pediatric imaging.
#41 Nephrogenic Systemic Fibrosis (NSF): Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/17783-nephrogenic-systemic-fibrosis-nsf
Healthcare providers are now aware of the harmful effects older GBCAs have on people with reduced kidney function. Your risk is much lower now that preventive measures are in place. […] Prior to 2019, the FDA reported 3,094 total cases of NSF, including 742 deaths. But there havent been any new cases in over 10 years. This is mainly because the FDA and healthcare community are aware of the effects of GBCA on people with kidney disease.
#42 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. […] 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. […] Many patients with nephrogenic systemic fibrosis have the triad of renal impairment, a proinflammatory state, and gadolinium exposure. […] The pathophysiology behind nephrogenic systemic fibrosis is unclear. […] Currently, there is no effective treatment for nephrogenic systemic fibrosis. […] Prevention of nephrogenic systemic fibrosis is the best practice. […] Nephrogenic systemic fibrosis is an important disease of which all physicians who order MRI with gadolinium-based contrast agents must be aware.
#43 Nephrogenic Systemic Fibrosis After Gadolinium-Contrast MRIlogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b
https://www.jwatch.org/na51867/2020/06/30/nephrogenic-systemic-fibrosis-after-gadolinium-contrast
Nephrogenic systemic fibrosis (NSF) â a severe and often fatal condition caused by collagen deposition in soft tissues and organs â occurs (rarely) in patients after receiving gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging. […] In this systematic review of 20 observational studies, researchers found no cases of NSF among >83,000 patients who had been exposed to newer GBCAs, but fewer than 20% of patients had any chronic kidney disease (<3% with stage 3â5 disease and 1% who were receiving dialysis). [...] However, interpreting the latter finding is problematic, because three of those four NSF patients had previous GBCA exposure outside the study setting. [...] Unfortunately, the number of patients with renal disease who were evaluated after use of newer gadolinium agents was relatively low and likely insufficient to allow definitive assessment of their risk. [...] Although some authorities suggest that NSF cases are nonexistent after newer gadolinium agents are used, this comprehensive analysis suggests that cases might occur occasionally. Prudent use of gadolinium among patients with severely limited renal function is advisable.
#44 Gadolinium-Induced Nephrogenic Systemic Fibrosis: Classification, Risk and Guidelines
https://consultqd.clevelandclinic.org/gadolinium-induced-nephrogenic-systemic-fibrosis-classification-risk-and-guidelines
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.
#45 Nephrogenic systemic fibrosis (NSF) – Questions and Answers in MRI
https://mriquestions.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. […] 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.