What is Nephrogenic Systemic Fibrosis (NSF)?

From the Guidelines

Nephrogenic systemic fibrosis (NSF) is a rare but serious condition characterized by fibrosis of the skin and internal organs that occurs primarily in patients with advanced kidney disease, strongly associated with exposure to gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) 1.

Key Characteristics of NSF

• NSF is a condition that primarily affects patients with advanced kidney disease, particularly those undergoing renal replacement therapy, with acute kidney injury (AKI), or at stages 4 or 5 chronic kidney disease (CKD) 1.
• The risk of NSF differs between gadolinium-based contrast media (GBCM) and can be stratified into three groups: group I (highest risk), group II (very low risk), and group III (likely very low risk but insufficient confirmatory evidence) 1.
• The risk of NSF increases with larger doses of group I GBCM, and the dose-related risk of NSF from group II and group III GBCM is unknown, but in general, the lowest diagnostic dose of GBCM should be used 1.

Prevention and Management of NSF

• To prevent NSF, patients with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m² should avoid gadolinium exposure whenever possible 1.
• If contrast is absolutely necessary, macrocyclic GBCAs (such as gadobutrol, gadoterate meglumine, or gadoteridol) should be used at the lowest possible dose, as these have a lower risk of causing NSF than linear GBCAs 1.
• Hemodialysis patients should undergo dialysis promptly after GBCA administration, ideally within 2-3 hours 1.
• There is no proven effective treatment for established NSF, though improvement in kidney function may help, and physical therapy is important to maintain joint mobility and prevent contractures 1.

Screening for Kidney Disease

• Kidney function screening prior to group II GBCM administration is optional, but it is necessary for group III GBCM administration in patients with eGFR less than 30 mL/min per 1.73 m² or AKI 1.
• The risk of NSF is very low for a standard dose (0.1 mmol/kg) of group II GBCM, even in patients with eGFR less than 30 mL/min per 1.73 m² or AKI 1.

From the Research

Definition and Characteristics of Nephrogenic Systemic Fibrosis (NSF)

• Nephrogenic systemic fibrosis is a progressive, potentially fatal, multiorgan-system fibrosing disease related to exposure of patients with renal failure to gadolinium-based contrast agents used in magnetic resonance imaging 2.
• It is characterized by thickening and hardening of the skin with fibrosis of the dermis, and can lead to significant disability and death 3, 4.
• The disease can affect various organs, including the skin, lungs, myocardium, and striated muscles, and is often associated with a "woody" texture of the skin, resembling "peau d'orange" 4.

Risk Factors for NSF

• Advanced kidney disease, particularly end-stage renal disease requiring dialysis, is a major risk factor for NSF 2, 3, 4, 5.
• Exposure to high-dose and specific gadolinium-based contrast agents, such as gadodiamide, increases the risk of NSF 2, 4, 6.
• Other potential risk factors include metabolic acidosis, iron overload, divalent ion disturbances, endothelial/vascular injury, and high erythropoietin doses 4.
• Patients with acute kidney injury or severe chronic kidney disease are also at increased risk of developing NSF 2, 3, 5.

Clinical Presentation and Diagnosis

• The clinical presentation of NSF can vary, but often includes red skin areas or plaques that develop over several weeks to painful thickened skin with a "woody" texture 4.
• Skin biopsy can reveal thickened collagen bundles, mucin deposition, proliferation of fibroblasts and elastic fibers, without inflammation 4.
• The diagnosis of NSF is often confirmed by biopsy, and the disease can be distinguished from other fibrosing disorders by its characteristic clinical and histological features 3, 4.