Sampling on ice will not yield reliable uric acid monitoring in rasburicase-treated patients

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.

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 (K_m) and activation energy (E_act) 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).

Although uricolysis increased at a higher temperature, incubation at 4°C did not arrest uricolysis entirely. The yielded K_m of 128μmol/L highlights that maximum uricolytic activity is reached at UA concentrations lower than those observed for TLS patients. Furthermore, the E_act 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.

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.