| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Letters |
1 Loma Linda University Medical Center Loma Linda, CA 92354
2 University of Pittsburgh Medical Center–Presbyterian Pittsburgh, PA
15213
WEB—This is a Web exclusive article.
Gadolinium has now been shown by High et al. [3] to be deposited in tissue of patients with NSF 4–11 months after contrast administration in areas of fibrosis usually in association with significant deposits of other cations such as iron, zinc, and calcium. This tissue deposition of gadolinium in NSF patients was also confirmed by Boyd et al. [4] who found the gadolinium deposited in areas of calcium phosphate deposition.
In addition to deposition of CD34 and procollagen-1 positive spindle cells and numerous collagen bundles, the NSF-involved tissue becomes a focus of deposition of high concentrations of gadolinium and other cations in the setting of severe renal dysfunction. Although other cofactors (such as proinflammatory conditions, acidosis, and elevated serum iron or phosphate concentrations) may be involved, the exact pathogenesis is unclear. The detected gadolinium is unlikely to represent gadolinium-based contrast media because this should diffuse freely between the interstitium and intravascular space and should be readily removed with hemodialysis. In fact, with the scanning electron microscopy technique used by High et al. [3], the tissue samples are washed in such a way that all soluble forms of gadolinium (including gadolinium-based contrast media) should be washed clear of the sample before analysis. Therefore, it seems highly likely that the detected gadolinium represents gadolinium (+3) ion released from the chelate by transmetallation within the tissue interstitium. Subsequently the free gadolinium ion likely binds to phosphate or other anions or a newly expressed binding protein intrinsic to the tissue. The ligand released from the chelate competitively binds with other cations, some of which may be insoluble and deposit in tissue. Alternatively, a newly expressed binding protein may serve as a scavenger for the deposition of other cations. This may help explain why a number of patients in our study had abnormal soft-tissue uptake of another cation, technetium, in the distribution of their NSF disease during bone scintigraphy.
Additional information was requested regarding the timing of dialysis for the NSF patients dialyzed on the same day as gadodiamide administration. Immediately after publication of our manuscript, this question was brought to our attention by Emanuel Kanal, of the University of Pittsburgh Medical Center and chair of the American College of Radiology Blue Ribbon Panel on MR Safety. He voiced the concern that if hemodialysis were significantly delayed after gadodiamide administration, the drug might have already escaped in significant volumes to a relatively dialysis-protected extravascular third space.
This led us to further investigate the precise relative timing of the dialysis sessions for these NSF patients. In our study 10 of 12 patients with gadodiamide-associated NSF were dialyzed at least once within 1–2 days of contrast administration without the prevention of NSF. Patients 1, 4, and 5 in Table 1 [2] were on daily hemodialysis for three consecutive days with dialysis starting 9 hours, 17 hours, and 18 hours after the injection of gadodiamide. In addition, patient 3 started daily dialysis for three consecutive days on the day after a late-night MRI (21 hours after contrast administration). In summary, we had four NSF patients who received daily dialysis for 3 consecutive days starting within 24 hours of contrast administration. We did not have any patients who were dialyzed immediately after the MRI examination.
Regarding the details of the dialysis therapy, all four patients were dialyzed with an intermittent hemodialysis technique. Patient 1 underwent dialysis with a large PSN dialyzer (Baxter) with only a flow of 200–300 mL/min for 3 hours. Patient 2 was dialyzed with a medium size Exeltra 170 dialyzer (Baxter) for 3 hours and 1 hour of isolated ultrafiltration with a blood flow of 300 mL/min. Patient 3 had 3-hour dialysis sessions with a PSN 120 dialyzer (Baxter) with a blood flow of 300–400 mL/min. Patient 4 had 3-hour dialysis sessions with a PSN 210 (Baxter) dialyzer with a blood flow of 300 mL/min. In summary, these patients predominantly under-went low-intensity dialysis because three of the four patients had acute hepatorenal syndrome and were relatively unstable.
In conclusion, daily low-intensity hemodialysis performed on 3 consecutive days after gadodiamide administration did not prevent the development of NSF in four patients whose dialysis was started 9–21 hours after contrast administration. The likely trigger for NSF is transmetallation of the gadolinium-based contrast media with release of gadolinium ion with binding to the involved tissue limiting or inhibiting its extraction with dialysis after this time period. It is quite possible that gadolinium-based contrast media triggers the pathogenesis of NSF within a short time (less than 9 hours after gadolinium-based contrast media administration). An alternative hypothesis is that the triggering process of transmetallation may take days to months to occur because of high initial contrast dose administration, poor renal clearance, and sequestration of gadolinium-based contrast media into relatively dialysis-protected third spaces. The latter hypothesis is further supported by the fact that a number of reported NSF patients have often had multiple administrations of gadolinium-based contrast media within a 3- to 12-month period before the development of NSF. Whether dialysis immediately or within a few hours after MRI can prevent NSF is unclear from our data. However, present data strongly suggest a dose–response relationship between these agents and NSF development. In patients with severely impaired renal function, the only means available to acutely decrease patient drug load is hemodialysis. Thus, given the lack of any consistently effective treatment for NSF, immediate hemodialysis after MRI as a potential preventive measure should continue to be strongly advised for all hemodialysis patients who receive gadolinium-based MR contrast agents [5]. For those patients who lack hemodialysis access, such as nondialysis or peritoneal dialysis patients, the risks of hemodialysis probably do outweigh the questionable potential benefit of NSF prevention.
References
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. R. Prince, H. Zhang, M. Morris, J. L. MacGregor, M. E. Grossman, J. Silberzweig, R. L. DeLapaz, H. J. Lee, C. M. Magro, and A. M. Valeri Incidence of Nephrogenic Systemic Fibrosis at Two Large Medical Centers Radiology, September 1, 2008; 248(3): 807 - 816. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
