Time

Prog #

Martin R. Prince¹, Honglei Zhang², Michael Morris³, Jennifer MacGregor⁴, Jeffrey Silbertsweig⁵, Marc E. Grossman⁴, Anthony M. Valeri⁴, Cynthia Magro¹, Robert DeLapaz⁴, Henry Lee¹, David N. Silvers⁴

¹Weill Medical College of Cornell University, New York, New York, USA; ²Weill Medcial College of Cornell University, New York, New York, USA; ³Columbia University , New York, New York, USA; ⁴Columbia University, New York, New York, USA; ⁵Rochefeller University, New York, New York, USA

Ten years of medical records were reviewed to identify biopsy-confirmed cases of NSF and the number of patients undergoing GBCA enhanced MRI.  Maximum risk of NSF, 8 of 22 (36%) patients, occured in dialysis patients with pro-inflammatory events receiving high-dose gadodiamide without undergoing dialysis for ≥ 3 days.  Dialysis within one day following gadodiamide reduces risk to 1/127 (0.8%).  Acute renal failure with rising serum creatinine is higher risk than severe chronic renal insufficiency.  Risk of NSF with single dose GBCA was 0 in 63597 patients.  A minority of NSF (7/25) cases were unrelated to GBCA exposure.

Thomas A. Hope¹, Robert J. Herfkens, Eli Weil

¹Kaiser San Francisco, San Francisco, California , USA

This study intends to determine the risk of developing Nephrogenic Systemic Fibrosis (NSF) in dialysis dependent patients and those with elevated creatinines who have received gadopentetate dimeglumine. No previous study has published an incidence using gadopentetate dimeglumine.  During the study period there were MRAs in 442 dialysis dependent patients and 3,065 patients with creatinines < 1.8. Our preliminary results show a lower prevalence of developing NSF in patients with renal disease than has previously been reported.

Martin A. Sieber¹, Thomas Frenzel, Philipp Lengsfeld, Joachim Hütter², Hubertus Pietsch¹

¹Bayer Schering Pharma AG, Berlin, Germany; ²Bayer Schering Pharma AG, Germany

Nephrogenic Systemic Fibrosis (NSF) is only observed in patients with severe renal dysfunction and a role for Gadolinium-based contrast agents (GBCAs) as a possible trigger has been suggested. The objective of this study was to evaluate the impact of prolonged circulation time of GBCAs on the onset of NSF-like signs in renal impaired rats. A prolonged circulation time for linear contrast agents due to reduced renal elimination correlated with an increased Gd retention in skin, in particular after administration of non-ionic linear GBCAs. For macro-cyclic compounds, no long-term retention of Gd in the skin could be observed.

Sameer M. Mazhar¹, Masoud Shiehmorteza¹, Chad A. Kohl¹, Jamey Allen¹, Michael S. Middleton¹, Claude B. Sirlin¹

¹University of California, San Diego, San Diego, California , USA

There have been increasing concerns of nephrogenic systemic fibrosis (NSF) in patients with chronic liver disease, as evidenced by the FDA’s black box warning cautioning against the use of gadolinium-based contrast agents in liver patients with renal insufficiency in the setting of hepatorenal syndrome or the perioperative liver transplantation period.  We performed a comprehensive review of the NSF literature to characterize NSF in patients with chronic liver disease.  A total of 291 unique patients were identified, 34 of whom (11.7%) had liver disease.  Analysis revealed that liver disease does not appear to be an independent risk factor for NSF.

Zeke W. Foster¹, Kendal Martin, Chad A. Kohl², Masoud Shiehmorteza², Sameer M. Mazhar², Lillian O. Pacheco², Jamey Allen², Claude B. Sirlin²

¹The Ohio State University School of Medicine, Columbus, USA; ²UCSD, San Diego, USA

Purpose: To determine the prevalence of nephrogenic systemic fibrosis (NSF) in patients with chronic liver disease exposed to gadolinium-based contrast agents.Methods: Retrospective review of 500 patients with chronic liver disease with gadolinium-enhanced MRI scans.Results: None of the 500 patients reviewed developed a fibrotic dermopathy consistent with NSF. Conclusions:  Liver disease does not appear to substantially increase the risk for NSF development.

Joseph P. Hornak¹, Brittany Lipchick¹, Melissa Monahan¹

¹RIT, Rochester, New York, USA

NMR relaxometric data of mixtures of gadodiamide with copper and zinc indicate different interactions between the contrast agent and two metals.  Two copper ions complex with the gadodiamide ligand DTPA-BMA.  No clear complex ratio was seen for the zinc.

Peter Caravan¹, Yan Wang, Marga Spiller

¹Massachusetts General Hospital, Charlestown, Massachusetts, USA

It is widely assumed that extracellular fluid Gd-based contrast agents do not bind to proteins.  We used relaxometry (NMRD) to demonstrate that commercial GdDTPA (ionic) and GdDTPA-BMA (non-ionic) contrast agents do exhibit weak protein binding and that the extent of binding depends on the specific protein and the specific contrast agent.  These results have implications for estimating in vivo Gd concentration from T1 changes, and may be important for understanding differences in the biological activity of these agents.

Martin A. Sieber¹, Thomas Frenzel, Philipp Lengsfeld, Joachim Hütter², Hubertus Pietsch²

¹Bayer Schering Pharma AG, Berlin, Germany; ²Bayer Schering Pharma AG, Germany

Several recent publications suggest a role for Gadolinium based contrast agents (GBCAs) as a possible trigger for Nephrogenic Systemic Fibrosis (NSF). The aim of the study was to evaluate the possible long-term retention of Gadolinium (Gd) in the skin of rodents following administration of different GBCAs. Gd-concentration in the skin was measured after application of linear non-ionic (Omniscan® and OptiMARK®); linear ionic (Magnevist®); macro-cyclic GBCAs (Gadovist®,  ProHance® and Dotarem®). Regarding the Gd-concentration in the skin, we observed statically significant differences between the different GBCAs classes.

Ivan Pedrosa¹, Philip Robson¹, Martin P. Smith¹, Andrew Wagner¹, Neil M. Rofsky¹, David Alsop¹

¹Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Magnetic Resonance (MR) imaging has played an important role in the characterization of renal tumors over the last years, particularly in the setting of impaired renal function where the nephrotoxic iodinated contrast agents used for computed tomography are not desirable. However, the recently reported association between gadolinium-contrast agents and the systemic disease nephrogenic systemic fibrosis has limited the use of these contrast agents in patients with moderate-to-severe renal insufficiency. Alternative imaging techniques for these patients that provide accurate differentiation between non-neoplastic and neoplastic renal masses based on their perfusion is mandatory in clinical practice. This abstract presents our initial experience with an arterial spin labeling (ASL) MR imaging technique, for the characterization of renal masses in patients with impaired renal function.