Treatment of Nephrogenic Systemic Fibrosis: Limited Options but Hope for the Future Douglas R. Linfert, Jane O. Schell, and Derek M. Fine Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland ABSTRACT Nephrogenic systemic fibrosis has now been linked to gadolin- ium-based contrast exposure in those with compromised kid- ney function. When present, symptoms can be quite devastating for the patient including severe pain and immobil- ity. Unfortunately there is a lack of a universally effective ther- apy at this time and the literature, reviewed in this article, is comprised of primarily case reports and small case series allow- ing few conclusions to be drawn. It is widely recognized that supportive management with physical therapy and aggressive pain management is essential. Resolution of renal function in acute kidney injury appears to attenuate disease in most cases and transplantation has been associated with variable success. Therapies with anecdotal benefit include extracorporeal photo- pheresis and intravenous sodium thiosulfate. Other interven- tions have shown limited success. As the mechanism becomes more readily understood, it is hoped that targeted therapy might prove more effective than currently available remedies. In all likelihood prevention will prove to be most effective in avoiding this devastating complication. Nephrogenic systemic fibrosis (NSF) has now been linked to exposure to gadolinium-based contrast (GBC) in those with compromised kidney function, particularly those with end-stage renal disease (ESRD). The pro- posed mechanism is the tissue deposition of the metal in patients, where prolonged half-life allows transmetalla- tion and dissociation of the ion. Free metal deposits in tissues setting off a cascade of events that are poorly understood. Part of this includes macrophage activation and recruitment of circulating fibrocytes with sub- sequent induction of edema and fibrosis. Unfortunately there is a lack of a universally effective therapy at this time. Several interventions described in this article, though effective in some cases, have not been reproducible. Table 1 outlines attempted therapies. Most of the available literature on treatment precedes the discovery of the GBC association. Therefore, as the mechanisms and the role of GBC become more readily understood, it is hoped that targeted therapy proves more effective than currently available remedies. Little is known about re-exposure to GBC during many of the described cases and it is certainly possible that some patients had ongoing exposures resulting in limited response or worsening of disease. When reviewing this literature and assessing ones own patients’ response to therapy, it is important to note that following recovery from NSF, patients may have contin- ued joint contractures and immobility. These chronic sequelae of NSF need to be distinguished from the acute or active disease process where patients usually experi- ence edema, severe pain, and other related symptoms. This distinction is critical to allow the correct diagnosis, which will significantly impact on management. Those with acute disease (recognized early) may benefit from some of the interventions to be discussed, while those with chronic residual contractures and immobility will likely not. It is imperative that all patients, regardless of acuity, receive physical and occupational therapy to maintain joint mobility. An aggressive pain regimen is also essen- tial to provide relief for often debilitating pain that attends this disease. Above all, prevention is most effec- tive in avoiding this devastating complication. Therapies Most Likely to Benefit Recovery of Renal Function Because all cases of NSF have been described in those with impaired renal function, including acute kidney injury (AKI), chronic kidney disease (CKD), and ESRD, it has been hypothesized that renal recovery might result in improvement. Indeed this was observed in several case reports where resolution of AKI resulted in regression of lesions (1–5). Pre- sumably, resolution of AKI allows clearance of GBC and other fibrotic mediators, though definitive evi- dence of this is not available. Address correspondence to: Derek M. Fine, MD; 1830 East Monument Street, Suite 416, Baltimore, MD 21205, or e-mail: dfine1@jhmi.edu. Seminars in Dialysis—Vol 21, No 2 (March–April) 2008 pp. 155–159 DOI: 10.1111/j.1525-139X.2007.00407.x 155 NSF: WHAT WE KNOW AND WHAT WE NEED TO KNOW