Early Treatment with Rasburicase and Kidney Replacement Therapy or Death in Patients with Tumor Lysis Syndrome

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Background: Rasburicase rapidly lowers plasma uric acid levels and is often used to treat hyperuricemia in patients with tumor lysis syndrome (TLS). Despite its potent biochemical efficacy, no study has rigorously examined whether rasburicase improves clinical outcomes in patients with TLS. Methods: We performed a multicenter cohort study of 1,694 consecutive adults hospitalized with TLS at 26 hospitals across the US from 2014 to 2023. Detailed data were collected by manual chart review. We used a target trial emulation (TTE) framework to examine outcomes in patients who received early treatment with rasburicase (within 12 hours of meeting TLS criteria) to those who did not. The TTE framework included strict eligibility criteria to mimic those that would be used in a hypothetical randomized trial, along with detailed multivariable adjustment for confounders to emulate randomized treatment assignment. The primary outcome was a composite of AKI requiring kidney replacement therapy (AKI-KRT) or death during hospital admission. Secondary outcomes included individual components of the primary outcome and alternate definitions for AKI. Results: Among 1,019 eligible patients (Figure 1A), 554 (54.4%) received rasburicase within 12 hours following TLS, and 377 (37.0%) had a primary outcome event. In the primary analysis, patients who received rasburicase within 12 hours had a lower odds of developing the primary outcome compared to those who did not (adjusted odds ratio, 0.64 [95% CI, 0.47–0.87)]. Similar findings were observed for secondary outcomes (Figure 1B). Conclusion: In this multicenter cohort study of hospitalized adults with TLS, the risk of AKI-KRT or death was considerably lower in those who received early treatment with rasburicase compared to those who did not.

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