Dear Dr. Lu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Feb 28 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols....

We look forward to receiving your revised manuscript.

Kind regards,

Tarek Samy Abdelaziz, MD,FRCP

Academic Editor

PLOS One

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“This work was supported by the Anhui Provincial Health and Health Research Project (2024Aa20292), the Anhui Province Traditional Chinese Medicine Inheritance and Innovation Research Project (2024CCCX128), the Special Research Fund for Analgesia and Sedation in Critical Care (AHEBM20250707M1), and the Natural Science Research Project of Anhui Higher Education Institutions (2023AH053168).”

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

The author(s) received no specific funding for this work.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

5. Thank you for stating the following financial disclosure:

“This work was supported by the Anhui Provincial Health and Health Research Project (2024Aa20292), the Anhui Province Traditional Chinese Medicine Inheritance and Innovation Research Project (2024CCCX128), the Special Research Fund for Analgesia and Sedation in Critical Care (AHEBM20250707M1), and the Natural Science Research Project of Anhui Higher Education Institutions (2023AH053168).”

At this time, please address the following queries:

a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

b) State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

c) If any authors received a salary from any of your funders, please state which authors and which funders.

d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

6. In the online submission form you indicate that your data is not available for proprietary reasons and have provided a contact point for accessing this data. Please note that your current contact point is a co-author on this manuscript. According to our Data Policy, the contact point must not be an author on the manuscript and must be an institutional contact, ideally not an individual. Please revise your data statement to a non-author institutional point of contact, such as a data access or ethics committee, and send this to us via return email. Please also include contact information for the third party organization, and please include the full citation of where the data can be found.

7. Please include a separate caption for each figure in your manuscript.

8. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

9. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

10. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

11. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: This is a well-designed retrospective cohort study addressing an important clinical dilemma in the management of sepsis-associated AKI. The large sample size, consistent mortality findings across multiple analyses, and dose-response exploration are notable strengths. The manuscript contributes valuable real-world evidence to an area with limited data.

Major Points:

Causality and Interpretation

The conclusions should be tempered to emphasize association rather than benefit. Statements implying safety or effectiveness should be clearly framed within the limitations of observational data.

Residual Confounding

Although propensity score matching was performed, residual differences in urine output and fluid balance remain clinically meaningful. These variables may reflect both treatment response and baseline severity and should be discussed more explicitly as potential mediators or confounders.

Data Availability Compliance

Please revise the Data Availability Statement to comply with PLOS ONE policy by explicitly stating that the data are derived from the MIMIC-IV database and providing access details.

CRRT Timing

Since one of the main concerns addressed by the study is delayed CRRT initiation, providing more granular data or discussion on time-to-CRRT would further strengthen the manuscript.

Minor Points:

Improve language clarity and reduce repetition, especially in the Discussion.

Ensure consistent terminology (e.g., “pre-CRRT furosemide use” vs “furosemide administration within 72 hours”).

Consider adding a brief clinical implication section to guide readers on how findings may inform practice without overstating conclusions.

Reviewer #2: This is a very good and novel study that addresses an important clinical question. The study is well designed, methodologically sound, and provides valuable insights with potential implications for clinical practice.

Comment 1:

Score Matching

Line 2-3: Very interesting title, but you don’t need to mention the statistical tests used in the study (Propensity Score Matching).

Comment 2:

Line 24-29:

Specify the precise objectives of your study; currently, you only state the aim.

Comment 2:

Line 76:

The introduction is very well written, clear, and effectively aligned with the study's core objectives. I suggest adding a paragraph that discusses the potential mechanisms by which pre-CRRT furosemide administration might influence mortality, to strengthen the clinical rationale and contextualize the study findings.

Line 82:

I recommend adding a dedicated subsection titled *“Study design, participants, and setting.” Additionally, the study design is not clearly described and should be explicitly stated to improve clarity and methodological transparency.

Line 94:

Include this criterion within the inclusion criteria (Line 87).

Line 136:

For Figure 1, the propensity score matching flow diagram is conceptually appropriate and consistent with a 1:1 matching approach. However, the figure lacks information on excluded unmatched patients and should be complemented by a clear description of the matching methodology and balance diagnostics to ensure transparency and reproducibility.

Line 140:

Please revise the manuscript to report baseline characteristics for the propensity score–matched cohort and present them after propensity score matching, as this approach is essential for reducing bias and controlling for confounding. Baseline characteristics before matching may also be reported; however, the primary focus should be on the post-matching results.

Line 176:

3.5. Subgroup analyses:

Please report the results directly with their statistical significance. Avoid interpreting confidence intervals or p-values. The Results section should focus on presenting the findings rather than discussing their statistical implications.

Line 185:

3.6. Sensitivity analyses:

I believe there is redundancy between this section and lines 154–158, which makes the presentation confusing. Please clarify how this section differs from lines 154–158 or consider consolidating the overlapping content to improve clarity, or combine with primary outcome paragraph.

Line 192:

3.7. Dosage and Prognosis:

Please clarify the furosemide dosing strategy, specifically whether it was administered as a continuous infusion over 24 hours or as intermittent dosing. This distinction is important, as it remains an area of debate in the literature and may influence clinical outcomes.

Line 213 – 216:

Please indicate whether there are previous studies worldwide that have assessed these outcomes (7-day, 90-day, ICU, and in-hospital mortality) in relation to furosemide use, and briefly contextualize the findings in relation to your findings.

**********

what does this mean?). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our Privacy Policy..-->

Reviewer #1: Yes: Elabbass Ali AbdelmahmuodElabbass Ali AbdelmahmuodElabbass Ali AbdelmahmuodElabbass Ali Abdelmahmuod

Reviewer #2: Yes: Mohamed A. AlbekeryMohamed A. AlbekeryMohamed A. AlbekeryMohamed A. Albekery

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Pre-CRRT furosemide and mortality in sepsis-associated AKI: A retrospective cohort study

PONE-D-25-46945R1

Dear Dr. Lu,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support....

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tarek Samy Abdelaziz, MD,FRCP

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments: