22-33: Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis is a multisystem disorder seen only in patients with CKD (primarily with an eGFR less than 15 mL/min/1.73 m², but rarely with a GFR of 15–29 mL/min/1.73 m²), AKI, and after kidney transplantation. Histopathologically, there is an increase in dermal spindle cells positive for CD34 and procollagen I. Collagen bundles with mucin and elastic fibers are also noted.

Nephrogenic systemic fibrosis was first recognized in hemodialysis patients in 1997 and has been strongly linked to use of contrast agents containing gadolinium. Incidence is projected to be 1–4% in the highest risk (ESRD) population that has received gadolinium, and lower in patients with less severe kidney dysfunction. Reassuringly, the incidence has decreased over time and is thought to result from modified preparations of gadolinium as well as carefully identifying individuals who should avoid exposure altogether. There is an FDA warning regarding avoidance of this agent for patients with an eGFR less than 30 mL/min/1.73 m².

Nephrogenic systemic fibrosis affects several organ systems, including the skin, muscles, lungs, and cardiovascular system. The most common manifestation is a debilitating fibrosing skin disorder that can range from skin-colored to erythematous papules, which coalesce to brawny patches. The skin can be thick and woody in areas and is painful out of proportion to findings on examination.

Several case reports and series describe benefit after treatment with corticosteroids, photopheresis, plasmapheresis, and sodium thiosulfate, but their true efficacy is unknown. Patients already on dialysis who absolutely require gadolinium typically receive prolonged hemodialysis on 3 consecutive days, but this is based on expert opinion rather than high-quality evidence.