Welcome to IM Department Meeting! Gadolinium Based Contrast Exposure and Risk of Nephrogenic Systemic Fibrosis Tonight’s Facilitators: Barbara Doerr, DO William Myers, DO Staci Smith, DO Michelle 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) o skeletal 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 pts o 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 risk o 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 angiography o chelates are excreted exclusively by the kidney Gadolinium Half Life o o o o 1.3 hrs if healthy 10 hrs at GFR of 20 - 40 mL/min 34 hrs if ESRD 1.9 - 2.6 hrs if HD follows administration Gadolinium Based Contrast Agents o Omniscan o launched in the U.S. in 1993 by GE o Magnevist o MultiHance o OptiMARK o ProHance Risk factors for NSF o renal impairment o hypercoagulable state o thrombotic events o recent vascular study o transplant failure Signs and Symptoms of NSF o o o o o burning skin itchy skin swelling tight and hard skin red or dark skin patches o contractures o stiffness in joints o trouble moving extremities o pain deep in the bones o muscle weakness o “woody” feel of skin o yellow scleral plaques NSF Upper Extremity o thick, hardened skin o brawny hyperpigmentation o distinct papules o subcutaneous nodules NSF Upper Extremity o soft-tissue swelling o flexion contractures of hand NSF o slightly raised and erythematous nodular plaques o linear, confluent regions of fibrosis Differential Diagnosis o scleroderma / systemic sclerosis o eosinophilic fasciitis o eosinophilia–myalgia syndrome Differential Diagnosis o Unlike scleroderma o NSF spares the face o lacks the serologic markers of scleroderma o symmetrical lesions o prefers trunk and extremities Punch Biopsy : Skin widening of subcutaneous septae w/ thick collagen bundles Histological Findings and Pathogenesis o o o o thick collagen bundles with surrounding clefts mucin deposition increased fibrocytes and elastic fibers increased factor XIIIa and mononucleated cells Topic Development: PICO oP Patient Population oI Intervention or Exposure oC Comparison Intervention oO Outcome 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 754759. 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 2000 o renal dysfunction pts o regardless of cause o not just HD pts, PD pts as well o other associations: o vascular sx o vascular thrombosis o scleral plaques The Patient: NSF: Report of a New Case o 39 yo AAM o ESRD on HD d/t HTN for 8 yrs o multiple medical problems o antiphospholipid ab syndrome o no other rheumatologic history o 3 yrs before hospital admission o stiff fingers and arms o thickening skin on calves and thighs o rapid progression to contractures The Patient- NSF: Report of a New Case o pt’s lab data -p 755 o autopsy results o extensive fibrosis o fibrosis around o plaque like changes translumbar HD cath across chest, extremities o pt expired after 45 o contractures min of ACLS o thickened pleura o dense collagenous bands o fibrotic cardiac tissue NSF: Report of a New Case o taut, waxy appearance o 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 section o 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 disease o systemic manifestations o muscle, pleura, diaphragm, myo and pericardium o initiating factors in NSF o tissue injury o hypercoagulable state Discussion - NSF: Report of a New Case o NSF involves aberrant fibrocyte recruitment o decrease EPO due to fibrogenic properties o NO consistent treatment proven effective Article o 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 pts o both 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 o discussed with Dermatology o stratified by gadolinium exposure o 0, 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 dialysis o 592 pts or 4% had CKD 3 – 4 o 6,636 total pts received gad from 2004-2006 o skin bx w/ immunoperoxidase staining for CD 34 NSF After Gadolinium Exposure o Results: o 849 total pts o 261 had 354 MRI scans o w/ gadolinium (Omniscan) o 1 time exposure in 191 pts o 2 exposures in 53 o 3 exposures in 13 o 4 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 Dialysis o overall NSF rate 0.5% (4 of 261) o 1.5% risk of NSF after one gad exposure o 98.5% did not develop NSF o odds ratio 6.67 w/ one exposure o 44.5 odds ratio with multiple exposures o skin lesions appeared within 2-3 mo o strong statistical association with NSF and gadolinium exposure NSF After Gadolinium Exposure o Results : CKD 3 – 4 pts o no patients discovered to have NSF o 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 low o increased exposure leads to increased risk o higher Ca, Phos, and Epo may be associated with increased NSF incidence o NO need for gad restriction in CKD 3- 4 o monitor skin for 4-6 mo if gad is used o consider dialysis immediately after exposure o kidney transplant therapy in future Concluding Points oA o Academic Detailing oR o Reminders oE o Enticements oA o Audit Concluding Points: Academic Details o Academic Detailing: o Medical knowledge o NSF o Patient care o Communication o OMM/OPP o Systems based practice o Physician interacts with healthcare system o Practice based learning o Physicians maintain knowledge and skills to provide ongoing pt care Osteopathic Considerations o myofascial release o indirect techniques o whole body approach Osteopathy in Action o NSF registry o collects info about NSF pts from all over the world o General Clinical Research Center at Yale University o e-mail : registermc @juno.com o CDC o www.cdc.gov o FDA o 1-800-FDA-1088 o www.FDA.gov Systems Based Practice o acute NSF: 58089 o chronic NSF: 5829 o 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 future o screening baseline kidney fxn / size o acute kidney injury vs CKD o CrCl –when not to use gadolinium o follow-up labs after gadolinium use o when to dialyze ESRD pts if GBCA used Enticements/ Systems Based Practice o MRI imaging: DRG 8897 o o o o MRI brain w/ contrast: $3,692 MRI brain w/o contrast: $2,255 MRI thoracic/lumbar spine w/ contrast : $2,465 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 safety o balance benefits and risks of GBCA’s o screen all pts with labs and history o GBCA’s should NOT be used if CrCl <30 o careful consideration if CrCl <60 o alternative imaging methods Conclusions: Take Home Points o monitor for skin manifestations after GBCA o follow labs after administration o do not exceed recommended dose o 0.1-0.2 mmol/kg o allow time for elimination before readministration Please Join Us Next Month o IM Journal Club o presented by Dr. Bryan o 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.