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

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Dear Editor,

Shenoy and colleagues report a large multicentre cohort of adults with established tumour lysis syndrome (TLS) in which severity of illness at or near TLS onset was abstracted manually from medical records; their finding that early rasburicase is associated with fewer episodes of kidney replacement therapy or death addresses a question randomised trials have left open for two decades.[1] Earlier responses covered time-zero alignment, odds versus risk and residual confounding.[2-4] We raise a further point, checkable against the paper.

The comparator's composition is reported inconsistently. The Results state that, of 571 patients not treated within 12 hours, 193 (33.8%) received rasburicase later and 378 (66.2%) never did; tables S5 and S6 use this split, so 898 patients (705 plus 193) received rasburicase in total. Yet the legend to supplementary figure S3 states that 1083 of 1276 patients (84.9%) received rasburicase within seven days, the window table S5 uses to define "no receipt", which would instead imply 378 (1083 minus 705) treated more than 12 hours but within seven days and 193 (1276 minus 1083) not treated within seven days. The histogram supports the latter: its first bar, about 65%, matches 705/1083 (65.1%), not 705/898 (78.5%). Table S5 contains a further inconsistency: 126 men in the late-treated column plus 312 in the never-treated column exceeds the 384 men reported among all 571 in table 1. The primary estimate does not depend on which version is correct, but the interpretation of table S6 and of the "early v no rasburicase" sensitivity analysis in figure 2 does. Could the authors state the correct group sizes, correct the affected text, tables and figures, and confirm that this sensitivity analysis used the intended never-treated comparator?

References

1. Shenoy T, Sanchez-Almanzar D, Dias JA, et al. Early treatment with rasburicase and risk of kidney replacement therapy and death in adults with tumour lysis syndrome: emulated target trial. BMJ 2026;394:e100040. doi: 10.1136/bmj-2026-100040
2. Ding G, Wang J, Wu J. Re: Early treatment with rasburicase and risk of kidney replacement therapy and death in adults with tumour lysis syndrome: emulated target trial. BMJ 10 August 2026. https://www.bmj.com/content/394/bmj-2026-100040/rr-1
3. Zeng D. Re: Early treatment with rasburicase and risk of kidney replacement therapy and death in adults with tumour lysis syndrome: emulated target trial. BMJ 4 August 2026. https://www.bmj.com/content/394/bmj-2026-100040/rr-0
4. Tuersun A. Re: Early treatment with rasburicase and risk of kidney replacement therapy and death in adults with tumour lysis syndrome: emulated target trial. BMJ 24 July 2026. https://www.bmj.com/content/394/bmj-2026-100040/rr

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

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

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

Check this box if you would like your letter to appear anonymously:: Last Name: ZhuFirst name and middle initial: JiaxingEmail:

zhujx35@mail2.sysu.edu.cn

Address: No.58 Zhongshan Er Road, Guangzhou 510080, ChinaOccupation: Phd studentOther Authors: Qingui ChenAffiliation: Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityBMJ: Additional Article Info: Rapid response