title: Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats.
abstract: The purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.
  
  
  
  A comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.6 mmol Gd/kg a week for 5 weeks (cumulative dose of 12 mmol Gd/kg) of gadodiamide or saline solution. The MR signal enhancement in the deep cerebellar nuclei was monitored by weekly magnetic resonance imaging examinations. One week after the final injection, the total Gd concentration was determined by inductively coupled plasma mass spectrometry in different regions of the brain including the cerebellum, plasma, cerebrospinal fluid, parietal bone, and femur.
  
  
  
  After the administration of gadodiamide, the subtotal nephrectomy group presented a significantly higher T1 signal enhancement in the deep cerebellar nuclei and a major increase in the total Gd concentration in all the studied structures, compared with the normal renal function group receiving the same linear Gd-based contrast agent. Those potentiated animals also showed a pronounced hypersignal in the choroid plexus, still persistent 6 days after the last injection, whereas low concentration of Gd was found in the cerebrospinal fluid (<0.05 μmol/L) at this time point. Plasma Gd concentration was then around 1 μmol/L. Interestingly, plasma Gd was predominantly in a dissociated and soluble form (around 90% of total Gd). Total Gd concentrations in the brain, cerebellum, plasma, and bones correlated with creatinine clearance in both the gadodiamide-treated groups.
  
  
  
  Renal insufficiency in rats potentiates Gd uptake in the cerebellum, brain, and bones.
authors.affiliation: From the *Guerbet Research and Innovation Department, Aulnay-sous-Bois; †Institut Curie, Centre de Recherche, PSL Research University; and ‡Université Paris-Sud, Université Paris-Saclay, CNRS, UMR-9187, INSERM, U1196, F-91405, Orsay, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Rasschaert
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Idée
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fretellier
authors.forename: Véronique
authors.initials: V
authors.lastname: Vives
authors.forename: Xavier
authors.initials: X
authors.lastname: Violas
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ballet
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
mesh_terms: D000818:Animals; D002529:Cerebellar Nuclei / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000503:physiopathology*; D012965:Sodium Chloride / Q000008:administration & dosage; D013054:Spectrophotometry, Atomic
chemical_list: D003287:Contrast Media; D012965:Sodium Chloride; C064925:gadodiamide; D019786:Gadolinium DTPA