Was There Something Rotten in Denmark: Nephrogenic System Fibrosis Cases Occurring in Copenhagen.

More than half of all serious adverse drug reactions are identified seven years after FDA approval. One recent and unusual example involves a syndrome initially termed nephrogenic dermatopathic fibrosis, and then called nephrogenic systemic fibrosis (NSF).

Nephrogenic Systemic Fibrosis Risk Assessment and Skin Biopsy Quantification in Patients with Renal Disease following Gadobenate Contrast Administration.

BACKGROUND AND PURPOSE: Nephrogenic systemic fibrosis following administration of intravenous gadobenate during MR imaging is rare. This study aimed to analyze any nephrogenic systemic fibrosis-related risks and quantify skin gadolinium levels in patients with impaired renal function but without nephrogenic systemic fibrosis who had received gadobenate. MATERIALS AND METHODS: In this retrospective study with a prospective skin biopsy phase, patients with estimated glomerular filtration rates of <60 mL/min/1.73 m2 undergoing contrast-enhanced MR imaging from July 2007 through June 2014 were screened for nephrogenic systemic fibrosis using a questionnaire. This was highly sensitive but not specific and reliably excluded nephrogenic systemic fibrosis if responses to at least 6 of the 8 questions were negative. If no nephrogenic systemic fibrosis was detected, a skin biopsy was requested. RESULTS: Of 2914 patients who met these criteria, 1988 were excluded for various reasons. Of the remaining 926 patients, 860 were screened negative for nephrogenic systemic fibrosis. Of these, 17 (2%) had estimated glomerular filtration rates of <15 mL/min/1.73 m2, 51 (6%) had levels of 15 < 30 mL/min/1.73 m2, 234 (27%) had levels of 30 < 45 mL/min/1.73 m2, and 534 (62%) had levels of 45 < 60 mL/min/1.73 m2. Of the 66 who were not cleared of nephrogenic systemic fibrosis by the questionnaire, 6 patients were evaluated by a dermatologist and confirmed not to have nephrogenic systemic fibrosis (no biopsy required). CONCLUSIONS: A diagnosis of nephrogenic systemic fibrosis was excluded in 860 patients with impaired renal function who were followed up and received gadobenate during MR imaging. In 14 such patients who underwent at least 1 gadobenate-enhanced MR imaging examination and did not have nephrogenic systemic fibrosis, gadolinium levels in the skin were exceedingly low.

A Systematic Review of 639 Patients with Biopsy-confirmed Nephrogenic Systemic Fibrosis.

Background Although nephrogenic systemic fibrosis (NSF) affects the use of gadolinium-based contrast agents (GBCAs) in MRI, there continues to be limited knowledge because of the small number of patients with NSF. Purpose To perform a systematic review of NSF. Materials and Methods PubMed database was searched by using the term "Nephrogenic systemic fibrosis" from January 2000 to February 2019. Articles reporting details on individual patients with NSF diagnosis on the basis of both clinical presentations and biopsy confirmation were included. Data were pooled and authors were contacted for clarifications. Rates of NSF were compared through 2008 versus after 2008 and for group I versus group II GBCAs, assuming equal market share. Results Included were 639 patients from 173 articles. Data regarding sex were found for 295 men and 254 women. Age at NSF symptom onset was reported for 177 patients (mean, 49 years ± 16 [standard deviation]; age range, 6-87 years). There were 529 patients with documented exposure to GBCAs including gadodiamide (n = 307), gadopentetate dimeglumine (n = 49), gadoversetamide (n = 6), gadobutrol (n = 1), gadobenate dimeglumine (n = 1), multiple (n = 41), and unknown (n = 120). Among patients with previous exposure, only seven patients were administered GBCA after 2008, yielding a lower rate of NSF after 2008 (P < .001). There were motion limitations in 70.8% (296 of 418) of patients, indicating a more serious debilitation. Associated factors reported for NSF included exposure to GBCA group I (P < .001), dialysis, proinflammatory conditions, hyperphosphatemia, ß-blockers, and epoetin. For 341 patients with follow-up, 12 patients were cured and 72 patients partially improved including one during pregnancy. Among those 84 patients reported as cured or improved, in 34 patients cure or improvement occurred after renal function restoration. Four deaths were attributed to NSF. Conclusion Although 639 patients with biopsy-confirmed nephrogenic systemic fibrosis were reported, only seven were after gadolinium-based contrast agent exposure after 2008, indicating that regulatory actions and practice changes have been effective preventive measures. Improvement and sometimes cure with renal function restoration are now possible. © RSNA, 2019 See also the editorial by Davenport in this issue.

Nephrogenic systemic fibrosis: A survey of the use of gadolinium-based contrast agents in Ghana.

INTRODUCTION: The aim of this study is to identify current practice of administration of gadolinium-based contrast agents (GBCAs) in Ghana. METHOD: A total of 13 MRI (magnetic resonance imaging) facilities were sent a survey questionnaire to request information on their current practice with the use of GBCAs. RESULTS: Gadodiamide, a high risk GBCA accounted for 67% of first line agents. 5 (42%) had a departmental protocol on the administration of GBCAs with regards to its association with nephrogenic systemic fibrosis (NSF). Of the 8 that use gadodiamide, 3 check kidney function in all patients, 2 check in selected patients, and 3 do not check at all. All 3 that screen all patients do not use contrast if the patient has an eGFR (estimated glomerular filtration rate) of 30-59 ml/min, 1 considers other modality; and if the patient has an eGFR of <30 ml/min, 2 do not use contrast but consider other modality, however 1 continues with the high risk agent. CONCLUSION: Gadodiamide is widely used, with varied practice in screening for renal function, and risk factors associated with NSF. Current evidence shows that it is advisable to administer macrocyclic agents in patients with compromised renal function. It is also imperative to establish local guidelines in line with international guidelines in order to minimize the incidence of NSF.

Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study).

OBJECTIVE: To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. METHODS: Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 µmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at -15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. RESULTS: Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = -1.4 %, 95%CI = (-7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. CONCLUSION: Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. KEY POINTS: • Contrast-induced nephropathy (CIN) is a potential problem following gadolinium administration for MRI. • Meglumine gadoterate (Gd-DOTA) appears safe, even in patients with chronic kidney disease. • Gd-DOTA only caused a temporary creatinine level increase in 1/70 such patients. • No case or sign of NSF was detected at 3-month follow-up.

Contrast-induced nephropathy and nephrogenic systemic fibrosis: minimizing the risk.

INTRODUCTION: Contrast-enhanced cross-sectional imaging is essential to the urologist's practice. Traditionally, patients with impaired renal function could not be imaged with a computed tomography (CT) scan with contrast due to the risk of contrast-induced nephropathy (CIN). These patients could alternatively be imaged by magnetic resonance imaging (MRI) with gadolinium. However, the recent identification of the association between nephrogenic systemic fibrosis (NSF) and gadolinium administration has created significant challenges for urologists and radiologists when faced with the need for evaluation with contrast-enhanced cross-sectional imaging. In this review, we summarize the most comprehensive articles discussing both NSF and CIN and present a straightforward, evidence-based algorithm to determine the appropriate approach to cross-sectional imaging for all patients, as well as future directions regarding cross-sectional imaging. MATERIALS AND METHODS: A MEDLINE literature search for review articles from 1966 to August 2009 was performed. Selected additional articles for specific topics were also reviewed. This search yielded a total of 25 articles for NSF and 28 for CIN that were reviewed. RESULTS: The pathophysiology and risk factors of NSF and CIN are discussed, as well as potential interventions to decrease either morbidity or incidence. A multidisciplinary (urologist, nephrologist, radiologist) evidence-based algorithm is introduced for managing patients in need of cross-sectional imaging. CONCLUSIONS: The associated risks of contrast-enhanced, cross-sectional imaging has created significant challenges for urologic evaluation. We propose an evidence-based approach to guide patient therapy, which can minimize patient risk and physician anxiety, while simplifying the decision-making process.

Risk of nephrogenic systemic fibrosis in liver transplantation patients.

OBJECTIVE: The purpose of our study was to evaluate the exposure of our institution's liver transplantation population to gadolinium-based contrast agents and assess the rate of nephrogenic systemic fibrosis (NSF) within this unique group. MATERIALS AND METHODS: Institutional review board approval was obtained for a retrospective review of medical records of patients who had undergone liver transplantation at our institution between 1997 and 2008. Informed consent was not required. Demographic information, history of gadolinium-based contrast agent exposure, stage of chronic kidney disease (CKD), and evidence of NSF were recorded. RESULTS: A total of 2142 patients who had undergone liver transplantation at our institution between 1997 and 2008 were identified. Of this total, 33% (709/2142) had documented gadolinium-based contrast agent exposure peritransplantation. Patients in CKD1 and 2, CKD3, CKD4, and CKD5 comprised 50% (352/709), 28% (200/709), 8% (60/709), and 14% (97/709), respectively. Of patients in CKD5, 76% (74/97) required dialysis. Thorough review of all patients' medical records identified one biopsy-confirmed case of NSF in the 709 patients. This patient was also in CKD5 and required dialysis. CONCLUSION: Within our institution, only 0.1% (1/709) of all liver transplantation patients exposed to gadolinium-based contrast agents or 1.4% (1/74) of CKD5 patients requiring dialysis had biopsy proof of NSF. This incidence is consistent with the rate of NSF in all patients exposed to gadolinium-based contrast agents regardless of liver transplantation reported in the literature. Therefore, liver transplantation may not be an independent risk factor in development of NSF in patients exposed to gadolinium-based contrast agents.

Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines.

PURPOSE: To retrospectively determine the incidence of nephrogenic systemic fibrosis (NSF) in a large academic medical center after the adoption of restrictive gadolinium-based contrast agent (GBCA) administration guidelines. MATERIALS AND METHODS: For this retrospective HIPAA-compliant study, institutional review board approval was obtained and the requirement for informed consent was waived. Restrictive GBCA guidelines were adopted in May 2007. The guidelines (a) require a recent serum creatinine level measurement in any patient who is aged 60 years or older and/or at risk for renal disease, (b) limit the maximal weight-based GBCA dose administered to any patient with an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/m(2) to 20 mL, and (c) prohibit the administration of any GBCA in patients who have an eGFR lower than 30 mL/min/m(2) and/or are undergoing chronic dialysis treatment (except in emergency situations). The electronic medical records were searched for all contrast material-enhanced magnetic resonance (MR) imaging examinations performed during the post-guidelines adoption period between January 2008 and March 2010 and the pre-guidelines adoption and transitional period between January 2002 and December 2007. Separate pathology records were searched for biopsy-confirmed cases of NSF during the same study periods. The incidences of NSF during the pre-guidelines adoption and transitional period and post-guidelines adoption period were compared by using the paired Z test. RESULTS: A total of 52,954 contrast-enhanced MR examinations were performed during the post-guidelines adoption period. Of these 52,954 examinations, 46,464 (88%) were performed in adult patients with an eGFR of 60 mL/min/m(2) or higher or presumed normal renal function and 6454 (12%) were performed in patients with an eGFR of 30-59 mL/min/m(2). Thirty-six patients with an eGFR lower than 30 mL/min/m(2) underwent contrast-enhanced MR imaging for emergent indications. Review of the pathology records for January 2008 to September 2010 revealed no new cases of NSF resulting from GBCA exposure. CONCLUSION: After restrictive guidelines regarding GBCA administration were instituted, no new cases of NSF were identified among 52,954 contrast-enhanced MR examinations, including those performed in patients with an eGFR lower than 60 mL/min/m(2).

Nephrogenic systemic fibrosis, in patients with end-stage kidney disease on dialysis, in the greater Auckland region, from 2000-2006.

AIM: Nephrogenic systemic fibrosis (NSF) is a rare and serious disease characterised by thickening and hardening of the skin with fibrosis of the dermis with CD34-positive fibrocytes. NSF occurs in patients with renal failure and has been linked to exposure of gadolinium contrast agents. The Auckland region has a population of 1.3 million with consultation and dialysis services for patients with end stage kidney disease provided by two separate renal units. The aim of this study was to determine the incidence and frequency of NSF in the Auckland region and determine the risk based on exposure to gadolinium based contrast agents. METHODS: A retrospective case notes review of all patients with end stage kidney disease under the care of the renal services between 1(st) January 2000 and 31(st) December 2006 was undertaken. All cases of proven or suspected NSF were identified. Using a picture archive and communications support system all imaging and exposure to contrast was identified. RESULTS: Three cases of biopsy proven NSF and two further cases of clinical NSF were identified. In all cases there was exposure to Gadolinium. This risk of NSF on exposure to any gadolinium based contrast agents was 0.67%. Gadodiamide was used in one institution where all five cases of NSF were seen, gadodiamide was used in 1% of patients in the other institution with no recognised cases. CONCLUSION: The incidence of NSF is low with the greatest risk on exposure to linear, non-ionic chelates, with no ethnic predisposition.

Revisiting nephrogenic systemic fibrosis in 6 kidney transplant recipients: a single-center experience.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a fibrotic disorder occurring in patients with renal dysfunction. Exposure to gadolinium (Gd)-based contrast agents (GBCAs) during renal impairment is associated with development of NSF. METHODS: A cross-referenced search of kidney transplantation and radiology databases at a single institution revealed the prevalence of NSF in the transplant population. Clinical records and skin biopsy specimens from 6 patients with kidney transplant given a diagnosis of NSF were reviewed to identify contributing factors. RESULTS: Between January 1999 and December 2006, NSF was diagnosed in 6 of 705 patients with kidney transplant (0.9%). Renal function was impaired in all patients. Of 33 patients with kidney transplant exposed to GBCAs, 5 (15.2%) developed NSF. Disease onset ranged from 7 days to 11 months after exposure to GBCAs. All 5 patients exposed to GBCAs who developed NSF were also treated with a beta-blocker and clinical improvement was observed with discontinuation. The sixth case NSF appeared unrelated to Gd, without a known exposure, and testing of tissue via mass spectrometry revealed no Gd. Symptoms of NSF in this patient disappeared after administration of darbepoetin was switched from subcutaneous to intravenous injection. One patient with NSF who manifested the highest Gd level in tissue died 22 months after disease onset. LIMITATIONS: The study represents the retrospective experience of only a single center. CONCLUSIONS: NSF can develop in kidney transplant recipients with altered graft function. In these patients, exposure to GBCAs appears associated with development of NSF. The role of beta-blockers in the course of the disease merits further investigation.

Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases.

The aim of this article is to review the published cases of nephrogenic systemic fibrosis (NSF) in Japan. The Japanese medical literature database and MedLine were searched using the keywords NSF and nephrogenic fibrosing dermopathy (January 2000 to March 2009). Reports in peer-reviewed journals and meeting abstracts were included, and cases with biopsy confirmation were selected. 14 biopsy-verified NSF cases were found. In seven of eight patients reported after the association between gadolinium-based contrast agent (GBCA) and NSF was proposed, GBCA administration was documented: five received only gadodiamide; two received both gadodiamide and gadopentetate dimeglumine. In four cases, the amounts of contrast agent were registered: two received only a single dose (0.1 mmol kg(-1) body weight) whereas the other two received 7-15 ml (the body weight was not disclosed) for each MR examination. Five patients had multiple injections of GBCA before NSF developed. Except for one patient in whom renal assessment was not reported, none of the patients had an estimated glomerular filtration rate >30 ml min(-1) 1.73 m(-2) and all received dialysis. 5 of the 8 patients (63%) in whom GBCA exposure was confirmed were treated with peritoneal dialysis. Skin lesion of the lower extremity was the first symptom in 12 patients (86%), whereas 2 patients had primarily symptoms from the upper extremity. In three cases, GBCA was administered even after onset of the NSF symptoms because of the physicians' lack of knowledge about the possible association between GBCA and NSF. NSF is found among Japanese end-stage renal failure patients even after examinations using a single dose.

Prevalence of NSF following intravenous gadolinium-contrast media administration in dialysis patients with endstage renal disease.

PURPOSE: To evaluate the prevalence of nephrogenic systemic fibrosis (NSF) in a patient population being at highest risk for developing this disease and to evaluate possible risk factors. MATERIALS AND METHODS: The radiological records of 552 patients with ESRD being on hemodialysis (HD) or peritoneal dialysis (PD) were retrospectively reviewed to identify whether the patients underwent MR-examinations with or without intravenous administration of GBCA. In case of exposure to GBCA, the number of contrast injections, the benchmark and the cumulative doses of GBCA, and possible cofactors regarding pathogenesis of NSF were recorded. Diagnosis of NSF was confirmed either by deep skin biopsy or by review of medical and histopathological records. Data of NSF patients were compared with data of dialysis patients who did not develop NSF after MR-examinations. RESULTS: 146 dialysis patients underwent MRI without i.v.-administration of GBCA. No case of NSF was observed in this patient population. 195/552 patients proved to have a total number of 325 well-documented exposures to GBCA. Seven different types of GBCA were used during these MR-examinations. NSF prevalence rate was 1.6%. One patient died of NSF. Three different types of GBCA were involved in 6 NSF cases. 4/6 proved to be confounded cases. The cumulative dose of GBCA, history of thrombosis, recent surgery, and the combination of HD and PD proved to be significant cofactors for the development of NSF (p<.05). No significant difference regarding residual renal clearance (p=.898) and residual urine volume (p=.083) was found between NSF and non-NSF patients. CONCLUSION: The prevalence of NSF proved to be much lower in this high risk patient group being exposed to GBCA compared to the literature. NSF was not observed in ESRD patients undergoing MRI without administration of GBCA. Our data support a positive association between cumulative dose of GBCA and development of NSF. No positive association was found between residual renal clearance and residual urine volume and NSF.

Prevalence of nephrogenic systemic fibrosis in renal insufficiency patients: results of the FINEST study.

PURPOSE: Nephrogenic systemic fibrosis (NSF) is characterized by widespread tissue fibrosis, mainly affecting the skin. Gadolinium chelates have been implicated in the onset of NSF in patients with renal impairment (RI). The FINEST study (FIbrose Néphrogénique SysTémique) was designed to determine the prevalence of NSF after magnetic resonance imaging (MRI) in French RI patients. MATERIALS AND METHODS: We studied all patients with RI who had at least one MRI examination during a one-year period, with or without gadolinium chelate administration. Data were collected retrospectively from 9 Nephrology Departments in France, and included sex, age, renal function, type of gadolinium administered, and subsequent cutaneous disorders. If a patient presented a cutaneous disorder, a skin biopsy was performed to confirm the diagnostic. RESULTS: The 308 eligible patients had a mean age of 59.9 years, 59% were men, and 54% had stage 5 RI. 75% of those 308 patients received a Gadolinium chelate. Among those patients who received a gadolinium chelate, 76% received gadoterate, 20% gadopentetate, 3% gadodiamide and 1% gadobenate. No cutaneous disorders were recorded after MRI. CONCLUSION: These results confirm that NSF is a rare disease. Based on a reported frequency, approximately 3.5% in patients with glomerular filtration rate <30ml/min/1.73m(2)), some cases should have been observed in our study which included 308 patients. Most patients received gadoterate, a macrocyclic gadolinium chelate for which no case of NSF has been observed worldwide. This suggests that more stable macrocyclic agents may be less likely to induce NSF.

Ten-year experience with nephrogenic systemic fibrosis: case-control analysis of risk factors.

OBJECTIVES: To analyze all cases of nephrogenic systemic fibrosis (NSF) at our institution and to compare them with controls. METHODS: After the institutional review board approval, 13 biopsy-proven NSF cases were identified. Ten cases had complete records and were compared in a case-control format with 10 age- and sex-matched, dialysis-dependent controls. Analyzed risk factors included single and cumulative gadolinium dose, medication and transplant history, and serum electrolytes at the time of gadolinium exposure. RESULTS: There were 1.9% of dialysis-dependent, gadolinium-exposed patients who developed NSF. There was no difference in gadolinium dose, transplant history, or serum electrolytes. Seven of 10 cases and 3 of 10 controls were treated with erythropoietin (P = 0.13). At the time of NSF diagnosis, 7 of 10 cases were on immunosuppressive therapy. Two of 7 cases developed NSF only after immunosuppressive therapy was initiated. Two of 10 controls were on immunosuppressive therapy (P = 0.06). CONCLUSIONS: All cases of NSF occurred in dialysis-dependent, gadolinium-exposed patients. Associations between immunosuppressive and erythropoietin therapies and NSF need further investigation.

Risk factors for NSF: a literature review.

Emerging evidence linking gadolinium-based contrast agents (GBCAs) to nephrogenic systemic fibrosis (NSF) has changed medical practice patterns toward forgoing GBCA-enhanced magnetic resonance imaging (MRI) or substituting other imaging methods, which are potentially less accurate and often radiation-based. This shift has been based on reports of high NSF incidence at sites where a confluence of risk factors occurred in patients with severe renal dysfunction. This review article explores the factors that affect NSF risk, compares risks of alternative imaging procedures, and demonstrates how risk can be managed by careful selection of GBCA dose, timing of injection with respect to dialysis, and other factors. Nearly half of NSF cases are a milder form that does not cause contractures or reduce mobility. It appears that eliminating even a single risk factor can reduce NSF incidence/risk at least 10-fold. Elimination of multiple risk factors by using single-dose GBCA, dialyzing dialysis patients quickly following GBCA administration, avoiding GBCA in acute renal failure while serum creatinine is rising, and avoiding nonionic linear GBCA in renal failure patients may reduce NSF risk more than a thousand-fold, thereby allowing safe GBCA-enhanced MRI in virtually all patients. J. Magn. Reson. Imaging 2009;30:1298-1308. (c) 2009 Wiley-Liss, Inc.

Nephrogenic systemic fibrosis in liver disease: a systematic review.

Nephrogenic systemic fibrosis (NSF) may develop in patients with liver disease, a fact highlighted by Food and Drug Administration (FDA) announcements cautioning against the use of gadolinium-based contrast agents (GBCAs) in select liver disease patients. The purpose of this systematic literature review is to characterize the risk of NSF in patients with liver disease. All published articles on NSF from September 2000 through August 2008, were identified via PubMed searches and examination of articles' reference lists. Two reviewers independently read each article and identified unique patients with biopsy-proven or suspected NSF. Data on demographics, liver status, renal status, and GBCA exposure were collected. A total of 324 articles were reviewed, with 108 articles containing case descriptions of 335 unique NSF patients. After excluding the 95/335 (28%) patients in whom the presence or absence of liver disease was uncertain, liver disease was confirmed present in 41/239 (17%) patients. Renal insufficiency could be assessed in 35 of the liver disease patients; severe renal insufficiency, defined as a glomerular filtration rate (GFR) or estimated GFR (eGFR) <30 mL/min/1.73 m(2) or dialysis requirement, was present in 34/35 (97%) patients. The lone patient who developed NSF with mild/moderate renal insufficiency was atypical and received a total gadodiamide load of 0.76 mmol/kg over a 10-week period periliver transplantation. The published medical literature demonstrates that patients with liver disease who develop NSF also have severe renal insufficiency, suggesting that liver disease does not confer a risk for NSF beyond that of the underlying renal insufficiency. J. Magn. Reson. Imaging 2009;30:1313-1322. (c) 2009 Wiley-Liss, Inc.

Large sample of nephrogenic systemic fibrosis cases from a single institution.

OBJECTIVES: To estimate and stratify the risk of development of nephrogenic systemic fibrosis (NSF) in well-defined at-risk subpopulations from a large single institution, and to perform a single-institution case series study of patients with biopsy-proven NSF. DESIGN: Retrospective cohort of patients exposed to gadolinium-based contrast agents (GBCAs) at a single institution during an 8-year period (January 1, 1999, to December 31, 2006), and a case series study of patients with biopsy-proven NSF. SETTING: A primary, secondary, and tertiary health care center that treated more than 2.2 million outpatients and had 135 000 hospital admissions in 2007. Patients A total of 94 917 patients exposed to GBCAs; patients at risk for NSF (3779 patients on hemodialysis, 1694 patients with renal transplants, and 717 patients with liver transplants, a well-defined subgroup that includes patients at risk for reduced renal function); and 61 patients with a clinical diagnosis of NSF. MAIN OUTCOME MEASURE: Risk estimate for NSF. RESULTS: The risk of development of NSF is 1.0% for patients who undergo hemodialysis (8 of 827), 0.8% for patients with renal transplantation (4 of 527), and 0% for patients with liver transplantation at our institution (0 of 327). CONCLUSIONS: Despite the limitations, this study, which reviewed a large number of patients who underwent intravascular GBCA injections, demonstrates a 77-fold higher risk of NSF among patients who undergo hemodialysis and a 69-fold higher risk in patients with renal transplantation. This increased risk is thought to be associated with poor clearance of most GBCAs.

Nephrogenic systemic fibrosis after gadopentetate dimeglumine exposure: case series of 36 patients.

PURPOSE: To retrospectively assess the association between gadopentetate dimeglumine exposure at magnetic resonance imaging and the development of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval. Informed consent was waived. A search of medical and pathologic records was performed to identify patients with NSF that was diagnosed between January 1998 and December 2007. Patients with known exposure to gadolinium-based contrast agents other than gadopentetate dimeglumine were excluded. Medical records were then reviewed for gadopentetate dimeglumine exposure, renal status, concomitant diseases, timing of NSF symptom onset, date of NSF diagnosis, and clinical outcome. Skin gadolinium deposition was assessed for those patients with adequate available tissue. Spearman rank correlations were estimated to assess the relationship between the dose of gadopentetate dimeglumine and the time to onset of NSF. RESULTS: Thirty-six patients (mean age, 62.6 years; range, 30-83 years) had been exposed to gadopentetate dimeglumine prior to NSF onset. All had stage 5 chronic kidney disease and all but one were undergoing dialysis at the time of exposure. NSF developed within 3 months after the last gadopentetate dimeglumine exposure (range, 1-59 months) in 21 (66%) of 32 patients. The patients had been exposed to median cumulative gadopentetate dimeglumine volumes of 35, 40, 85, and 117.5 mL over the 3, 12, and 24 months and up to 11 years preceding the onset of NSF, respectively. Patients who received higher cumulative and total gadopentetate dimeglumine doses had a higher risk of developing NSF than did those who received lower doses (odds ratio = 1.2). Twenty (56%) of 36 patients died, with a median interval of 18 months between NSF symptom onset and death. CONCLUSION: NSF develops in patients with renal impairment after exposure to gadopentetate dimeglumine in a dose- and time-dependent manner. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531082160/-/DC1.

Evaluation of the incidence of nephrogenic systemic fibrosis in patients with moderate renal insufficiency administered gadobenate dimeglumine for MRI.

AIM: To determine the incidence of nephrogenic systemic fibrosis (NSF) in stage 3 chronic kidney disease patients following intravenous exposure to gadobenate dimeglumine. MATERIALS AND METHODS: A prospective study was performed on 168 consecutive patients at a single institution with stage 3 chronic kidney disease who underwent clinically-indicated contrast-enhanced magnetic resonance imaging (MRI) examinations with gadobenate dimeglumine from January 2007 to March 2008. All patients were contacted by phone by investigators 3 months after MRI to verify the presence or absence of NSF signs or symptoms. If signs or symptoms suggestive of NSF developed, dermatologic referral was made and confirmatory skin biopsy performed if indicated. RESULTS: One hundred and eighty contrast-enhanced MRI examinations with gadobenate dimeglumine were performed on the 168 patients. Twenty patients were lost to follow-up, but 160 incidents of contrast medium exposure were followed up for 3-months and 105 incidents were followed up for 6 months. The mean contrast medium dose per weight was 0.093 mmol/kg (range 0.042-0.153 mmol/kg). The mean estimated creatinine clearance was 50.4 ml/min/1.73 m(2) (range from 30-59 ml/min/1.73 m(2)). Ten patients developed skin rashes during the 3-month follow-up period, but none were confirmed to represent NSF (0% prevalence rate). No other signs or symptoms of NSF were reported. CONCLUSION: Based on this limited study, NSF does not appear to occur in patients with stage 3 chronic kidney disease exposed to intravenous gadobenate dimeglumine for MRI at standard dosing of approximately 0.1 mmol/kg.