It may be possible for patients with renal insufficiency, including those with end-stage kidney disease (ESKD), to undergo MRI using potentially safer preparations of gadolinium-based contrast agents (GBCAs) with “very low, if any” risk of the feared nephrogenic systemic sclerosis (NSF). ¹

In contrast to the so called “linear” chelates of gadolinium (eg, gadodiamide, gadopentetate), “cyclic” GBCA’s (eg, gadoteridol) have not been clearly associated with NSF. ² A Veterans Administration study involving gadoteridol identified no cases of NSF among the 141 patients on hemodialysis following 198 exposures. ² In fact, the 2017 American College of Radiology (ACR) Manual on Contrast Media reports the risk of NSF with cyclic chelates as “very low, if any”. ¹ A 2020 systematic review and meta-analysis involving 4931 patients with stage 4 or 5 chronic kidney disease (ie, GFR <30mL/min per 1.73 m²) failed to find any cases of NSF after receiving group II GBCAs (eg, non-linear, including cyclic).^2a When a cyclic GBCA is used in patients with ESKD, however, hemodialysis has been recommended as soon as possible after MRI. ³

GBCAs are chelates with 2 major components: gadolinium and either a linear or cyclic ligand. Cyclic ligands bind to gadolinium more avidly, resulting in lower probability of circulating renally-cleared free gadolinium which when deposited in tissue is thought to potentially trigger NSF.²

Although NSF is characterized by progressive fibrosis of skin and soft tissue, it may involve multiple organs with an estimated 30% mortality rate. ⁴

 Bonus Pearl: Did you know NSF is really a new disease, with no evidence of its existence before 1997?

 

Contributed by Richard Newcomb, MD, Mass General Hospital, Boston, MA.

 

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References

1. “Nephrogenic Systemic Fibrosis”. In ACR Manual on Contrast Media; Version 10.3; May 31, 2017. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf
2. Reilly RF. Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 2008;3:747-51. https://www.ncbi.nlm.nih.gov/pubmed/18287249.                                                   2a.  Woolen SA. Shankar PR, Gagnier JJ, et al. Risk of nephrogenic systemic fibrosis in patients with stage 4 or 5 chronic kidney disedse reciving a group II gadolinium-based contrast agent: A systematic review and meta-analysis. JAMA Intern Med 2020;180:223-230. Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis | Chronic Kidney Disease | JAMA Internal Medicine | JAMA Network
3. Wang Y, Alkasab TK, Nari O, et al. Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 2011;260:105-111.  https://www.ncbi.nlm.nih.gov/pubmed/21586680
4. Schlaudecker JD, Bernheisel CR. Gadolinium-associated nephrogenic systemic fibrosis. Am Fam Physician 2009;80:711-14. https://www.aafp.org/afp/2009/1001/p711.pdf

 

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