title: Sampling on ice will not yield reliable uric acid monitoring in rasburicase-treated patients.
abstract: OBJECTIVE
  Rasburicase is administered to prevent hyperuricemia and counteract the consequences of tumour lysis syndrome (TLS). The benefit of monitoring uric acid (UA) concentrations in rasburicase-treated patients is questionable as spuriously low values are most frequently encountered. The manufacturer recommends a cold sample handling procedure to arrest ex vivo uricolysis. Contrariwise, it was recently considered that the temperature does not significantly affects rasburicase uricolysis. We here present a thorough investigation on rasburicase kinetics in clinical samples.
  
  
  METHODS
  UA was spiked in sera from rasburicase-treated patients at varying concentrations, divided in three fractions for incubation at 4°C, 22°C or 37°C and measured at fix time points. The Michaelis-Menten constant (Km) and activation energy (Eact) were estimated by linear regression and the Arrhenius equation, respectively. Additionally, UA concentrations retrieved in sera of rasburicase-treated patients were retrospectively studied (3.5years period).
  
  
  RESULTS
  Although uricolysis increased at a higher temperature, incubation at 4°C did not arrest uricolysis entirely. The yielded Kmof 128μmol/L highlights that maximum uricolytic activity is reached at UA concentrations lower than those observed for TLS patients. Furthermore, the Eactof 27kJ/mol corresponds to only a modest logarithmic decrease of the uricolytic capacity by 4-5% per -1°C. In routine practise, 'negative' UA concentrations were observed during 88.5% of the rasburicase therapy episodes, even when samples were stored at 4°C.
  
  
  CONCLUSIONS
  In contrast to manufacturer's guidelines, simple cooling of the sample will not arrest the temperature-dependent uricolysis provoked by rasburicase and therefore not yield reliable UA monitoring.
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Paediatrics and Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Depreter
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Stove
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: joris.delanghe@ugent.be.
authors.forename: Joris
authors.initials: J
authors.lastname: Delanghe
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006074:Gout Suppressants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D014503:Urate Oxidase / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood*
chemical_list: D006074:Gout Suppressants; C469709:rasburicase; D014527:Uric Acid; D014503:Urate Oxidase
keywords: Fasturtec®; Kinetics; Rasburicase; Uric acid; Uricolysis; Uricolytic activity