Early treatment with rasburicase and risk of kidney replacement therapy and death in adults with tumour lysis syndrome: emulated target trial.

Abstract

To examine the association between early rasburicase treatment and acute kidney injury requiring kidney replacement therapy or death among patients with tumour lysis syndrome (TLS). Emulated target trial. 36 US hospitals. 1276 adults (≥18 years) admitted to hospital between 2014 and 2023 with active haematological malignancy or solid tumour with metastases, high tumour burden, or laboratory findings and clinical features consistent with TLS. The primary outcome was a composite of acute kidney injury requiring kidney replacement therapy or death during the index hospital admission. A key secondary outcome was 90 day mortality. Outcomes were compared between patients who received rasburicase within 12 hours after TLS onset and those who did not, using logistic regression with inverse probability of treatment weighting to adjust for confounding. Among 1276 patients included in the analysis, 705 (55.3%) received rasburicase within 12 hours after TLS onset. Among patients treated within 12 hours of TLS onset, rasburicase was administered at a median of 5.0 hours (interquartile range 3.1-7.5 hours). Patients who received rasburicase had higher uric acid concentrations than those who did not (median 0.71 <i>v</i> 0.59 mmol/L (11.9 <i>v</i> 9.9 mg/dL)); however, severity of illness was well balanced after applying inverse probability of treatment weighting. Early rasburicase treatment was associated with a lower risk of acute kidney injury requiring kidney replacement therapy or death (32.7% <i>v</i> 42.0%; adjusted odds ratio 0.67, 95% confidence interval 0.52 to 0.88; P<0.001). Results were consistent across multiple sensitivity analyses and for 90 day mortality (adjusted odds ratio 0.71, 0.54 to 0.94). Among adults with TLS, early rasburicase treatment for TLS was associated with about one third lower risk of acute kidney injury requiring kidney replacement therapy or death compared with delayed or no rasburicase treatment.