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  • Title: Sampling on ice will not yield reliable uric acid monitoring in rasburicase-treated patients.
    Author: Depreter B, Stove V, Delanghe J.
    Journal: Clin Biochem; 2016 Dec; 49(18):1390-1395. PubMed ID: 27129796.
    Abstract:
    OBJECTIVES: 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. DESIGN AND 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 Km of 128μmol/L highlights that maximum uricolytic activity is reached at UA concentrations lower than those observed for TLS patients. Furthermore, the Eact of 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. CONCLUSION: 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.
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