Comparing Refrigeration to Immediate Room Temperature Testing for Uric Acid Monitoring in Rasburicase-Treated Patients

Abstract

Abstract Rasburicase (Rb) is a uric acid (UA) degrading enzyme important for treating tumor lysis syndrome. Rb retains activity at room temperature (RT), so specimens collected for UA-level monitoring require cooling protocols: collecting samples in pre-chilled tubes, transporting on ice, centrifuging at 4°C, and testing within 4 hours. In our laboratory, specimens are tested within ~45 minutes of collection. Our clinical study objective was to determine if we could ease these pre-analytical requirements to improve compliance while maintaining accuracy. 50 pairs of specimens were transported and stored either on ice or at RT. All were tested at 3 time points post-collection: immediately upon arrival to the laboratory (~45 minutes), 90 minutes, and 135 minutes. Linear regression analysis of iced versus RT specimens showed a high correlation with R2= 0.99 (p< .0001) and bias of -2.4%, which indicate no clinical differences observed in UA concentrations between 1-12 mg/dL, at the immediate testing time point. UA levels did not significantly decrease in the iced specimens at any time point. However, UA levels had decreased by >10% in 16 of the 50 RT specimens after 90 minutes. Linear regression analysis of specimens tested immediately on ice versus RT specimens tested after 135 minutes yielded an R2= 0.84 (p< .0001) and bias of -17.5%. The best model from a stepwise regression was composed of the number of binned Rb half-lives (0-2 or >2) that had passed since the patients’ Rb infusion (Rb half-life= 1080 minutes; p< .0001) and the Rb dose (3 mg versus 6 mg, p< .0001), which explained ~50% of the UA variation (R2= 0.48, p< .0001). Keeping Rb dose constant, RT specimens tested within 0-2 half-lives post-infusion had an additional 24% average decrease in UA concentration compared to those tested after >2 half-lives. Similarly, keeping Rb half-life constant, RT specimens from patients given a 6-mg dose had an 18% decrease in UA concentration compared to patients given a 3-mg dose. Using a total allowable error (TEA) of 17% as a threshold, 96%, 60%, and 38% of RT specimens tested within 0-2 half-lives were within TEA at the immediate (45-minute), 90-minute, and 135-minute time points, respectively. In contrast, 100%, 96%, and 88% of RT specimens tested after >2 half-lives were within TEA at the immediate (45-minute), 90-minute, and 135-minute time points, respectively. UA concentrations are not clinically different in RT or iced specimens, as long as tested within ~45 minutes post-collection. Specimens tested within 2 Rb half-lives post-infusion have significantly decreased UA levels if kept at RT for >90 minutes. Laboratories that can test UA levels rapidly after specimen collection may be able to validate alternative pre-analytical methods to transporting and testing on ice.