title: Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case-control study from Denmark.
abstract: BACKGROUND
  Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disease associated with exposure to gadolinium-based contrast agents (GBCA) in patients with renal insufficiency.
  
  
  OBJECTIVE
  To report the prevalence of NSF in a well-defined cohort of patients with renal insufficiency exposed to GBCA, to investigate if GBCA-unexposed controls showed signs of NSF and to evaluate selected risk factors among NSF cases and GBCA-exposed controls.
  
  
  METHODS
  A study among GBCA-exposed patients with renal insufficiency (n=565) was conducted to identify cases of NSF. The NSF cases found were age and sex matched and clinically compared with GBCA-exposed and unexposed patients with renal insufficiency in a case-control study.
  
  
  RESULTS
  We identified 17 NSF cases. No signs of NSF were observed among the controls. The prevalence of NSF was 4·7%, highest among patients with chronic kidney disease (CKD) stage 5 exposed to GBCA and undergoing haemodialysis or peritoneal dialysis. Three NSF cases were identified among patients with CKD stage 3 and 4. Three patients developed NSF after macrocyclic GBCA exposure. NSF cases had a tendency to have higher serum phosphate concentrations than GBCA-exposed controls.
  
  
  CONCLUSIONS
  Our study supports the view that GBCA is a major risk factor for NSF. Importantly, we found that patients with CKD stage 3 and 4 can be at risk of NSF. NSF may also be triggered by macrocyclic GBCA. Further, we observed a trend for higher phosphate levels in NSF cases compared with controls. The important findings drawn from this case-control study indicate that NSF is not an overlooked condition among patients with renal insufficiency not exposed to GBCA.
authors.affiliation: Institute of Clinical Medicine, Department of Dermatology, MR Research Centre, Department of Nephrology, Department of Rheumatology and Department of Pathology, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-82000 Aarhus, Denmark.
authors.forename: T R
authors.initials: TR
authors.lastname: Elmholdt
authors.forename: M
authors.initials: M
authors.lastname: Pedersen
authors.forename: B
authors.initials: B
authors.lastname: Jørgensen
authors.forename: K
authors.initials: K
authors.lastname: Søndergaard
authors.forename: J D
authors.initials: JD
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Ramsing
authors.forename: A B
authors.initials: AB
authors.lastname: Olesen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D003287:Contrast Media / Q000009:adverse effects*; D005260:Female; D005682:Gadolinium / Q000009:adverse effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D054989:Nephrogenic Fibrosing Dermopathy / Q000097:blood / Q000139:chemically induced*; D010755:Organophosphates / Q000378:metabolism; D006435:Renal Dialysis / Q000379:methods; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D003287:Contrast Media; D010755:Organophosphates; D005682:Gadolinium