Nephrogenic Systemic Fibrosis, Kidney Disease, and Gadolinium

Nephrogenic systemic fibrosis (NSF), formerly known as nephrogenic fibrosing dermopathy (NFD), is now a major concern for nephrologists. This entity was first described in 1997 in renal transplant recipients with poor graft function (1). More than 215 cases of NSF have subsequently been described in the NFD/NSF registry, with increasing numbers of cases being reported (2). NSF is a fibrosing disorder that involves predominantly the skin but also affects systemic organs such as the liver, heart, lungs, diaphragm, and skeletal muscle (3). It is associated with severe physical disability and death when multisystem disease supervenes (3). The cause of NSF is unknown; however, underlying kidney dysfunction is present in all cases. Approximately 90% of the patients described in the registry have ESRD and are on either hemodialysis or peritoneal dialysis (2). The rest have chronic kidney disease (CKD) or developed NSF in the setting of acute kidney injury (AKI). Thus, underlying kidney disease is a requisite for NSF to occur. Because not all patients with kidney disease develop NSF, one must hypothesize that a trigger is required to set the “fibrosing process” into motion. What do we know about the histology of tissue fibrosis in NSF? Dermal spindle cells, the predominant cell type found in NSF biopsies, have an immunologic profile (CD34/procollagen I) that is identical to blood-borne cells, circulating fibrocytes (cF), which participate in normal wound healing (4). In the setting of tissue/endothelial injury, they enter tissues and engage in wound healing and scar formation. In NSF, however, this process differs from normal wound healing in that cF engage in this activity in the absence of a clinically evident wound. The disturbed environment of kidney disease may supply abnormal signals, which result in cF entry into normal tissues and induction of fibrosis (4). A logical first step to …