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Welcome to IM Department Meeting!
Gadolinium Based Contrast Exposure and Risk of Nephrogenic Systemic Fibrosis
Tonight’s Facilitators:Barbara Doerr, DOWilliam Myers, DOStaci Smith, DOMichelle Cacek, DO
Nephrogenic Systemic Fibrosis (NSF)
o originally named nephrogenic fibrosing dermopathy (NFD)
o manifestations initially thought to be confined to the skin
o systemic fibrosis on autopsy (NSF)oskeletal muscles ,diaphragm ,pleura ,dura
mater, pericardium & myocardium
Nephrogenic Systemic Fibrosis (NSF)
o predominately in pts with acute kidney injury or severely impaired renal function o CrCl less than 30
o no predilection for age, race, gender ,or location
o typically middle aged ptso reported in 8 yo children, as well as elderly
What’s the risk?
o risk of NSF estimated at 4.3 cases per 1,000 dialysis patients per year
o about 2.4 % for each time a CKD pt is exposed to gadolinium
o balancing benefit and risko majority of pts who receive Gd do not
develop NSF
What’s the issue with NSF?
o avoidance of GBCA’s o limited radiological studies
o roadblocks to specific dx
o litigation opportunities
September 12, 2007
Boxed Warning
o Gadolinium based contrast agents increase risk of NSF in pts with:o acute and chronic renal failure (GFR <
30)o acute renal insuffciency of any severity
due to hepatorenal syndrome or in perioperative liver transplant period
What is Gadolinium?
o nonionic, hyperosmolar (650 mosmol/kg) contrast agent
o metal with powerful magnetic properties o contrast for MR imaging or MR angiographyo chelates are excreted exclusively by the
kidney
Gadolinium Half Life
o 1.3 hrs if healthyo 10 hrs at GFR of 20 - 40 mL/mino 34 hrs if ESRDo 1.9 - 2.6 hrs if HD follows administration
Gadolinium Based Contrast Agents
o Omniscano launched in the U.S. in 1993 by GE
o Magnevisto MultiHanceo OptiMARKo ProHance
Risk factors for NSFo renal impairmento hypercoagulable stateo thrombotic eventso recent vascular studyo transplant failure
Signs and Symptoms of NSF
o burning skino itchy skino swelling o tight and hard skin o red or dark skin
patcheso contractures
o stiffness in joints o trouble moving
extremities o pain deep in the boneso muscle weaknesso “woody” feel of skino yellow scleral plaques
NSF Upper Extremity
o thick, hardened skin
o brawny hyperpigmentation
o distinct papules
o subcutaneous nodules
NSF Upper Extremityo soft-tissue swelling o flexion contractures of hand
o slightly raised and erythematous nodular plaqueso linear, confluent regions of fibrosis
NSF
Differential Diagnosis
o scleroderma / systemic sclerosis o eosinophilic fasciitis o eosinophilia–myalgia syndrome
Differential Diagnosis
o Unlike sclerodermao NSF spares the face o lacks the serologic markers of
sclerodermao symmetrical lesions
oprefers trunk and extremities
Punch Biopsy : Skin
widening of subcutaneous septae w/ thick collagen bundles
Histological Findings and Pathogenesis
o thick collagen bundles with surrounding clefts
o mucin depositiono increased fibrocytes and elastic fiberso increased factor XIIIa and mononucleated
cells
Topic Development: PICO
o PPatient Population
o IIntervention or Exposure
o CComparison Intervention
o OOutcome
Question ???
o What degree of kidney disease should we not use gadolinium based contrast agents ?
Article
o Nephrogenic Fibrosing Dermopathy/ Nephrogenic Systemic Fibrosis: Report of a New Case with Literature Review
o Daram, et al. AJKD, Vol 46, No 4, 2005, pp 754-759.
Evidence Based Medicine
o Nephrogenic Fibrosing Dermopathy /Nephrogenic Systemic Fibrosis: Report of a New Case with Literature Review
o Daram ,et al. o AJKD 2005
Introduction- NSF: Report of a New Case
o first cases of NSF recognized in 2000o renal dysfunction pts
o regardless of causeo not just HD pts, PD pts as well
o other associations:o vascular sxo vascular thrombosiso scleral plaques
The Patient: NSF: Report of a New Case
o 39 yo AAM o ESRD on HD d/t HTN for 8 yrso multiple medical problems
oantiphospholipid ab syndrome
o no other rheumatologic history o 3 yrs before hospital admission
ostiff fingers and armsothickening skin on calves and thighsorapid progression to contractures
The Patient- NSF: Report of a New Case
o pt’s lab data -p 755o fibrosis around
translumbar HD catho pt expired after 45
min of ACLS
o autopsy resultso extensive fibrosiso plaque like changes
across chest, extremities
o contractureso thickened pleurao dense collagenous
bandso fibrotic cardiac tissue
NSF: Report of a New Case
o taut, waxy appearanceo cobblestone pattern o fig 1B
NSF: Report of a New Case
o chest wall w/thick dermis
o dense white fibrous bands in septa
NSF: Report of a New Case
haphazardly arranged collagen bundles w/ clefts
NSF: Report of a New Case
o diaphragm sectiono fibrous bands o fibroblast like cells
NSF: Report of a New Case
dendritic projections on CD34 cells CD45 RO cells
Discussion- NSF: Report of a New Case
o NFD is not merely a cutaneous diseaseo systemic manifestations
omuscle, pleura, diaphragm, myo and pericardium
o initiating factors in NSFo tissue injuryo hypercoagulable state
Discussion - NSF: Report of a New Case
o NSF involves aberrant fibrocyte recruitmento decrease EPO due to fibrogenic properties
o NO consistent treatment proven effective
Articleo Nephrogenic Systemic Fibrosis After
Exposure to Gadolinium in Patients with Renal Failure
o Othersen, J. et al, Nephrology Dialysis Transplantation, Sept 21, 2007, p 1-7.
Evidence Based Medicine
o Nephrogenic Systemic Fibrosis After Exposure to Gadolinium in Patients with Renal Failure
NSF After Gadolinium Exposure
o Purpose:o analyze NSF incidence o association of NSF with gadolinium
exposure in CKD ptsoboth pre-dialysis and dialysis pts
o determine if increased gadolinium exposure increases NSF
NSF After Gadolinium Exposure
o Methods:o 849 total pts in 5 yr time span (2001-2006)o Nephrology at Medical University of SC
odiscussed with Dermatology
o stratified by gadolinium exposureo0, 1, or greater than 1
o statistical association between NSF rate and gad exposure
o statistical association of increasing gad exposure and NSF occurrence
NSF After Gadolinium Exposure
o Methods:o CKD pts NOT on dialysiso 592 pts or 4% had CKD 3 – 4o 6,636 total pts received gad from 2004-
2006o skin bx w/ immunoperoxidase staining for
CD 34
NSF After Gadolinium Exposure
o Results:o 849 total ptso 261 had 354 MRI scans
ow/ gadolinium (Omniscan)o1 time exposure in 191 ptso2 exposures in 53o3 exposures in 13o4 exposures in 5
NSF After Gadolinium Exposure
Gadolinium Exposure
NSF Incidence
Never 0%
One time 1.1%
Greater than one time 2.9%
NSF After Gadolinium Exposure
o Results: Pts on Dialysiso overall NSF rate 0.5% (4 of 261)o 1.5% risk of NSF after one gad exposureo 98.5% did not develop NSFo odds ratio 6.67 w/ one exposure
o44.5 odds ratio with multiple exposures
o skin lesions appeared within 2-3 moo strong statistical association with NSF
and gadolinium exposure
NSF After Gadolinium Exposure
o Results : CKD 3 – 4 ptso no patients discovered to have NSFo incidence estimated at <0.2%o possibly due to only 4% have CKD 3-4
NSF After Gadolinium Exposure
o Conclusions:o NSF incidence is very lowo increased exposure leads to increased risko higher Ca, Phos, and Epo may be
associated with increased NSF incidenceo NO need for gad restriction in CKD 3- 4o monitor skin for 4-6 mo if gad is usedo consider dialysis immediately after
exposureo kidney transplant therapy in future
Concluding Points
o Ao Academic Detailing
o Ro Reminders
o Eo Enticements
o Ao Audit
Concluding Points: Academic Detailso Academic Detailing:
o Medical knowledgeoNSF
o Patient careo Communicationo OMM/OPP o Systems based practice
oPhysician interacts with healthcare systemo Practice based learning
oPhysicians maintain knowledge and skills to provide ongoing pt care
Osteopathic Considerations
o myofascial releaseo indirect techniqueso whole body approach
Osteopathy in Action
o NSF registry o collects info about NSF pts from all over the
worldo General Clinical Research Center at Yale
Universityo e-mail : registermc @juno.com
o CDCo www.cdc.gov
o FDAo 1-800-FDA-1088o www.FDA.gov
Systems Based Practice
o acute NSF: 58089o chronic NSF: 5829o include CKD staging: 585.-o principal procedure
o MRI imaging: 8897
Systems Based Practice
o Cerebral a. occlusion w/ cerebral infarction
DRG: 43491
$5,246.24 Medicare
o Cerebral a. occlusion w/ cerebral infarction
plus acute NSF DRG: 43491,
58089
$7,877.25 Medicare
Reminders
o Carepath in futureo screening baseline kidney fxn / sizeo acute kidney injury vs CKDo CrCl –when not to use gadoliniumo follow-up labs after gadolinium useo when to dialyze ESRD pts if GBCA used
Enticements/ Systems Based Practiceo MRI imaging: DRG 8897o MRI brain w/ contrast: $3,692o MRI brain w/o contrast: $2,255o MRI thoracic/lumbar spine w/ contrast :
$2,465o MRI thoracic/lumbar w/o contrast: $2,144
Audit
o How can we measure outcomes and progress?
o Practice habits changed in the future?
Conclusions : Take Home Points
o interest of pt safetyo balance benefits and risks of GBCA’s
o screen all pts with labs and historyo GBCA’s should NOT be used if CrCl
<30o careful consideration if CrCl <60
o alternative imaging methods
Conclusions: Take Home Points
o monitor for skin manifestations after GBCAo follow labs after administration o do not exceed recommended dose
o 0.1-0.2 mmol/kgo allow time for elimination before
readministration
Please Join Us Next Month
o IM Journal Clubo presented by Dr. Bryano laryngeal reflux and proton pump
inhibitors
References
o Nephrogenic Fibrosing Dermopathy /Nephrogenic Systemic Fibrosis: Report of a New Case with Literature Review.Daram ,et al. AJKD 2005.
o Nephrogenic Systemic Fibrosis After Exposure to Gadolinium in Patients with Renal Failure. Othersen, J. et al, Nephrology Dialysis Transplantation, Sept 21, 2007, p 1-7.
Happy Halloween !!
Trick or treat
References
• www.cdc.gov• www.fda.gov• Gadodiamide-Associated Nephrogenic
Systemic Fibrosis: Why Radiologists Should Be Concerned . Dale R. Broome et al. AJR 2007; 188:586-592.
• Adverse Reactions to Gadolinium Contrast Media: A Review of 36 Cases. Murphy,et al. AJR, Oct 1996:847-849.
