Authors' recommendations: NSF is a recently described and uncommon condition for which research remains in a preliminary stage. Apart from its invariable occurrence in patients with kidney disease, basic epidemiologic information (incidence, length of time post-exposure for development, prevalence, natural history, and risk factors other than GBCA exposure) is unavailable or highly variable and based on descriptive reports, as is an empirical understanding of underlying disease mechanisms.Although published analytic studies are generally consistent in finding an association with gadolinium, most studies titled “case-control” are more accurately classified as cross-sectional, and any causal role for GBCAs is incompletely documented. Treatment research is restricted to the descriptive: guidelines from the US, Canada, Europe, and Japan are not clearly based on rigorous evaluations of evidence for epidemiology, prevention, or treatment.In this context, the three specific questions added to TAP’s charge (page 1) are incompletely answered, at best. Grobner (2008) summarizes a clinical approach that agrees with available consensus guidelines (Leiner, 2009) and recognizes limitations in the knowledge base:“Patients with ESRD on dialysis are at high-risk to develop NSF after exposure to linear Gd-chelates. Though not yet proven, we believe that reduced or negligible urine production, a marker of poor residual renal function, is another risk factor, potentially explaining the sporadic development of NSF in all ESRD patients after GBCA exposure. Patients with CKD stages 4 and 5 as well as those with acute insufficiency are also at risk to develop NSF, but to a lesser degree. Those with more preserved renal function, such as CKD stages 1-3 are at very low or no risk, although those with advanced stage 3 disease (eGFR, 31-40ml/min) may maintain some risk if exposed to multiple/high doses of GBCA nonionic linear chelate. Currently, this is a purely speculative risk as no such cases have been reported.” (Grobner, 2008).The conclusions of the single strongest study included here (the CDC’s case-control; Appendix Table 5) also deserve another iteration; in closing:“…this study shows an independent association between gadolinium-containing MRI contrast agents and the development of clinically apparent NSF, a relationship for which a biologically plausible explanation exists. Many issues remain to be clarified with respect to NSF, including the prevalence of this condition, possible cofactors, and the level of renal dysfunction that predisposes to the disease. Additional studies are needed to determine whether some gadolinium contrast agents are safer than others in this population and whether prompt dialysis after contrast administration can lessen the risk of this debilitating condition.” (Kallen, 2007).The lack of subjects to fill all shaded cells in Table 2 has argued for analytic studies to be analyzed as cross-sectional studies rather than calculation of the “classical“ case control cross-product odds ratio (Appendix Table 5). The existence of risk for NSF with GBCAs is increasingly credible, but only a single study (Kallen, 2007) explicitly estimates magnitude or considers contributions from other exposures.While NSF cases without GBCA exposure have been reported (Wahba, 2007; Coollidge, 2007; Kallen, 2007; Bahrami, 2009), the Yale NSF registry has yet to fulfill its potential in supplying subjects for all of the cells in Table 2. The literature discounts reports of cases without exposure or actually incorporates exposure into case definitions (Leiner, 2009), making rigorous documentation from credible sources essential to full understanding.

Project Status: Completed

URL for project: http://www4.va.gov/VATAP/docs/Gadolinium2010.pdf

Year Published: 2010

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: VA Technology Assessment Program

Contact Address: Liz Adams, VA Technology Assessment Program, Office of Patient Care Services (11T), VA Boston Healthcare System Room 4D-142, 150 South Huntington Avenue, Boston, MA 02130 USA Tel: +1 617 278 4469; Fax: +1 617 264 6587;

Contact Name: elizabeth.adams@med.va.gov

Contact Email: elizabeth.adams@med.va.gov

Copyright: VA Technology Assessment Program (VATAP)