What is Nephrogenic Systemic Fibrosis (NSF)?

Nephrogenic Systemic Fibrosis (NSF)

Nephrogenic Systemic Fibrosis (NSF) is a potentially debilitating and sometimes fatal systemic fibrotic condition that occurs almost exclusively in patients with acute kidney injury (AKI) or severe chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m² following exposure to gadolinium-based contrast agents (GBCAs). 1

Clinical Presentation and Pathophysiology

• NSF primarily manifests with skin and subcutaneous abnormalities including skin thickening, contractures, pruritus, and hyperpigmentation, as well as ocular findings such as scleral plaques 1
• Beyond cutaneous involvement, NSF can cause fibrosis of internal organs including the lungs, esophagus, and heart 1
• The development of NSF is triggered by exposure to GBCAs, though the exact mechanism remains poorly understood 1
• Symptoms may appear anywhere from the same day to approximately 10 years after GBCA exposure, with a median interval of 42 days 1
• Diagnosis requires a combination of clinical history, specific scoring criteria, and deep skin biopsy 1

Risk Factors

• The highest risk patients include those:

  • Undergoing renal replacement therapy (dialysis) 2
  • With acute kidney injury 1
  • With stage 4 or 5 CKD (eGFR < 30 mL/min per 1.73 m²) 1
  • Exposed to Group I GBCAs (linear agents), especially with repeated or higher-than-recommended doses 2

• The incidence of NSF in patients with AKI who received high-dose Group I GBCAs has been reported as high as 19% 1

• There are rare reports of NSF in patients with stage 3 CKD (eGFR 30-59 mL/min per 1.73 m²), though some of these reports have questionable validity 1

• No published reports exist of NSF in patients with eGFR ≥ 60 mL/min per 1.73 m² 1

GBCA Classification and Risk Stratification

GBCAs are categorized into three risk groups:

• Group I (highest risk): Linear GBCAs associated with nearly all unconfounded cases of NSF 2
• Group II (very low risk): Includes gadobenate dimeglumine and macrocyclic agents 2
• Group III (likely very low risk): Includes gadoxetate disodium, but with insufficient confirmatory evidence 2

Prevention and Management

• Screening for kidney function is optional for Group II GBCAs but necessary for Group III GBCAs 1
• For patients with eGFR < 30 mL/min per 1.73 m², Group II GBCAs should not be withheld if harm would result from not proceeding with an indicated contrast-enhanced MRI 1
• Always use the lowest diagnostic dose of GBCA possible 2
• For patients requiring dialysis, prompt hemodialysis after GBCA exposure may be beneficial, though evidence for efficacy is limited 3
• Non-contrast MRI techniques should be considered as first alternatives for patients with severe renal insufficiency 3
• Since implementation of guidelines restricting GBCA use in at-risk patients, NSF cases have dramatically declined to single digits annually 1

Treatment

• No uniformly effective treatments exist for NSF 4
• Recovery from AKI and successful renal transplantation may reverse or stabilize the disease in some cases 5
• Combined therapies including ultraviolet-A1 phototherapy, methotrexate, and steroids have been used with some success in halting disease progression 6

The most effective approach to NSF remains prevention through careful patient selection and appropriate GBCA use based on kidney function.