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

Abstract Objectives 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). Design Emulated target trial. Setting 36 US hospitals. Participants 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. Main outcome measures 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. Results 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 v 0.59 mmol/L (11.9 v 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% v 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). Conclusions 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.

Authors

Institutions

Publication Details

Journal
BMJ
Published
2026-07-23
DOI
https://doi.org/10.1136/bmj-2026-100040
Primary Topic
Methemoglobinemia and Tumor Lysis Syndrome
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Shahzad Shaefi, Mariam Charkviani, David E. Leaf, Naveed Jan et al.
BMJ
Methemoglobinemia and Tumor Lysis Syndrome
article

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

Shahzad Shaefi, Mariam Charkviani, David E. Leaf, Naveed Jan, Anushree C. Shirali, Vigneshwar Subramanian, Jeff Kaiser, KAVINDYA WICKRAMASINGHE, Robert Hayden, Meghan E. Sise, Rituvanthikaa Seethapathy, Shruti Gupta, Abinet M. Aklilu, Madison Edwards, Julie‐Alexia Dias, Akash Mathavan, Claude Bassil, Ann Steward LaCasce, Nadia Al Haddad, Audrey E Monson, Phuong Nguyen, Tomonori Takeuchi, Anip Bansal, Natalia Nombera-Aznaran, Neha Debnath, Stefania Renzi, Nivetha Subramanian, CZARINA T FALDU, Daniel Sanchez-Almanzar, Jasmine Nadayil, Todd Miano, Nikita Shah, Rushad Patell, A Mathavan, Jessica Shostak, Rachid Baz, Elizabeth Angus, Philippe Armand, Saieda A. Alleyne, Steven T Hoge, Clara Walling, Atif Nasim, Daniela Garcia, Eesha Verma, Amanda Renaghan, Aqeeb Ur Rehman, David J Turco, Rafia Ali, Victoria Lypka, Jian Ni, Michael GS Shashaty, Kyra Shelton, Raghu Radhakrishnan, Vaishnavi Jayakumar, Megan Kotzin, Shuchi Anand, Tushar Shenoy, Cyrilee Thompson, Susan Ziolkowski, Stephen Griffiths, Faith Obimdike, Sydney Chase, Chintan V Shah, Javier A Neyra, Brian P Donahue, Sarah Kaunfer, Christina HW Brotman, Anish Shah
article en

Abstract

Abstract Objectives 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). Design Emulated target trial. Setting 36 US hospitals. Participants 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. Main outcome measures 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. Results 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 v 0.59 mmol/L (11.9 v 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% v 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). Conclusions 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.

BMJVol. 394
Brigham and Women's Hospital (US), Beth Israel Deaconess Medical Center (US), Harvard University (US), University of New Mexico (US), National Institute of Informatics (JP), University of South Florida (US), Moffitt Cancer Center (US), University of Alabama at Birmingham (US), Yale University (US), University of Florida (US), Surgical Specialties (Canada) (CA), University of Tokyo Health Sciences (JP), Dana-Farber Cancer Institute (US), Hypertension Institute (US), Mass General Brigham (US), University of Virginia (US), University of Colorado Anschutz Medical Campus (US), Carnegie Mellon University (US), University of Pennsylvania (US), University of Brescia (IT), Florida College (US), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 10%
Methemoglobinemia and Tumor Lysis Syndrome
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.