Case-control study of gadodiamide-related nephrogenic systemic fibrosis

Marckmann, Peter; Skov, Lone; Rossen, Kristian; Heaf, James; Thomsen, Henrik S.

doi:10.1093/ndt/gfm261

Cited by 188 publications

(153 citation statements)

References 19 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…This suggests that the higher phosphate level in ESRD patients may be a risk factor for Gd 3þ release in vivo, as previously suggested by Marckmann et al (46). In normal serum the release of Gd 3þ was about 10 times lower with the ionic linear GBCAs than with the nonionic linear GBCAs (Fig.…”

Section: Role Of Complex Stability: Evaluation Of Marketed Productssupporting

confidence: 79%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Nephrogenic systemic fibrosis (NSF) is a potentially severe systemic disease typically characterized by fibrosis of the skin and connective tissues. The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury, proinflammatory state, the administration of high doses of erythropoietin, and more recently the use of gadolinium-based contrast agents (GBCAs). The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on animal experiments. The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.

show abstract

Section: Role Of Complex Stability: Evaluation Of Marketed Productssupporting

confidence: 79%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

View full text Add to dashboard Cite

show abstract

“…Lifetime gadodiamide doses in adult patients with disabling NSF were greater than in patients with nondisabling NSF or in controls. 40 NSF patients had mean 25-day symptom-free periods following gadodiamide administration. [40][41][42] Three months earlier, an Austrian nephrologist reported that five of nine CKD patients who had undergone gadodiamide-enhanced MRIs developed NSF.…”

Section: Nephrogenic Systemic Fibrosismentioning

confidence: 99%

“…40 NSF patients had mean 25-day symptom-free periods following gadodiamide administration. [40][41][42] Three months earlier, an Austrian nephrologist reported that five of nine CKD patients who had undergone gadodiamide-enhanced MRIs developed NSF. 43 In 2008, Marckmann reported that between 2001 and 2006, 18 % of CKD patients at Herlev Hospital with severe renal insufficiency had developed NSF following administration of high-doses of gadodiamide.…”

Section: Nephrogenic Systemic Fibrosismentioning

confidence: 99%

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

et al. 2012

View full text Add to dashboard Cite

Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye’s syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States’ NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common

show abstract

“…NSF tends to affect the middle-aged most often (mean age 46.4 years) (2,23); the oldest reported patient was 87 years old (23)(24)(25). There are currently nine pediatric cases in schoolchildren and adolescents (age 8-19 years), but no reported cases in infants (26).…”

Section: Epidemiologymentioning

confidence: 99%

“…In detail, there is a number of case reports or small case series of patients with NSF who had an acute occlusion of their dialysis access (23,43), required creation of arteriovenous fistula (23,50,51), an angioplasty (50), suffered from deep venous thrombosis (7,44), pulmonary embolism (52), antiphospholipid antibody syndrome (7,27,45,53), protein C deficiency (54,55), renal vein thrombosis of the transplanted kidney (8), an atrial clot (56), peripheral vascular occlusion (43), transient ischemic attacks (43), multiple brain infarcts (43), an episode of atheroembolism (45), graft failure (42,47,48,52,(54)(55)(56), shock (8,50), multiple myeloma (44), lymphoproliferative disorder (48), brain tumor (23), infections (7,48,50), nonspecific inflammation (42), systemic lupus erythematodes (57), hepatic disease (23,45,53), or metabolic acidosis (13,50,54,55). Marckmann et al (25) found in a small case-control study that among CKD patients exposed to Gd-CA those who developed NSF had higher serum calcium and phosphate levels and received higher doses of erythropoietin than those who did not. Grobner (13) found in his very small series of five affected patients that all had metabolic acidosis, while all unaffected patients (n ¼ 4) showed normal findings regarding pH and bicarbonate values.…”

Section: Co-morbiditymentioning

confidence: 99%

Nephrogenic systemic fibrosis: Clinical spectrum of disease

Mayr

Burkhalter

Bongartz

2009

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Nephrogenic systemic fibrosis (NSF) is a rare systemic fibrosing disorder that primarily affects the skin and the subcutaneous structures. Also, there are reports of involvement of deeper structures and organs in the human body, but the confirmation of systemic involvement is complicated by overlap of other disease processes that occur in patients with severe renal impairment. The disorder leads to significant disability and is an important contributing factor of death. Virtually all patients who developed NSF suffered from endstage renal disease (ESRD) or severe chronic kidney disease (CKD) or from an acute acquired kidney injury (AKI). There is an increase in evidence that a causal relation between gadolinium‐based contrast agents (Gd‐CA) and NSF is probable. Therefore, advanced kidney injury and the exposure to Gd‐CA are regarded as prerequisites to develop NSF. Overall, the prognosis is poor and there is no established therapy that shows a consistent benefit. The purpose of this review is to discuss the clinical spectrum of the disease. The clinical presentation, role of co‐morbidity in disease development and manifestation, time course, prognosis, outcome, and epidemiological aspects are especially reviewed. J. Magn. Reson. Imaging 2009;30:1289–1297. © 2009 Wiley‐Liss, Inc.

show abstract

Case-control study of gadodiamide-related nephrogenic systemic fibrosis

Cited by 188 publications

References 19 publications

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Nephrogenic systemic fibrosis: Clinical spectrum of disease

Contact Info

Product

Resources

About