PONE-D-24-26287High level of soluble tumor necrosis factor receptors is associated with lower residual diuresis volume in hemodialysis patients: An exploratory study.PLOS ONE

Dear Dr. Lacerda,

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Reviewers' comments:

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Comments to the Author

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: Yes

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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.

Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: While I think an interesting analysis the lack of longitudinal data is regrettable. I think the conclusions drawn from the work are not sufficiently corroborated by the data since it only reports a cross-sectional association between inflammatory markers and residual renal function. Also - the correlational analyses are conducted in the overall sample of 60 HD patients, a study population which also comprises 27 anuric patients. As such the dependent variable is zero for almost half of the population - which I think will very much affected the results. A subset analysis in those with sufficient RRF is indicated but will suffer from the small ample size.

Reviewer #2: This study looked at the relationship between serum inflammation-related molecules and the level of residual kidney function in a cross-sectional cohort of patients on chronic HD.

Comments:

Indicate why only patients who have been on HD for more than 6 months were included.

Indicate why you chose to look at residual kidney function as a binary variable and why the cut-off of 100ml/day. Consider running the analyses with residual kidney function as a continuous variable.

What was the average interval (in days, weeks, months, or years) between the DEXA study and the testing of residual kidney function?

What was the average interval (in days, weeks, months, or years) between the measurement of sTNF-R1 and sTNF-R2 and the testing of residual kidney function?

Indicate the type of vascular access used for HD in Tables 1 and 2. Depending on vascular access type distribution between the groups, include the vascular access in regression analysis and Table 4.

The authors state: “During the study, patients underwent HD sessions using low-flux dialysis membranes,” Clarify what ‘during the study’ means, how long the patients were in the study.

Before entering the study, were any patients on high-flux dialyzers? If so, how many HD sessions, on average, did they receive with high-flux dialyzers before being switched to low-flux dialyzers?

Were other urine tests obtained, such as urea nitrogen or creatinine, and if so, please report Kidney stdKt/V or kidney urea clearance, kidney creatine clearance, in Tables 1 and 2

Consider adding in the Discussion that, besides the fact that this study does not prove causality, the direction of the association is also uncertain, For example, high levels of inflammatory markers can be a consequence (at least partly) of low residual kidney function rather than the etiology of low residual kidney function, or both.

Limitations appear in two separate sections –on page 15 and 16. Needs to be consolidated into one section, before Conclusions,

Same for Conclusions, it needs to be consolidated, it is mentioned on page 15 ‘Inc conclusion’, and again the paragraph on page 16,

Reference 11 – did not cross over properly, missing authors, journal

Tables 3 and 4: a/g ratio: add in the legend what a/g denotes

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Reviewer #1: No

Reviewer #2: Yes:  Mariana Murea

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PONE-D-24-26287R1High level of soluble tumor necrosis factor receptors is associated with lower residual diuresis volume in patients on hemodialysis: An exploratory study.PLOS ONE

Dear Dr. Lacerda,

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 19 2025 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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 https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Te-Ling Lu

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Partly

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: No

Reviewer #3: Yes

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4. 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.

Reviewer #2: No

Reviewer #3: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors addressed the comments satisfactorily with one exception which regards the following comment:

Comment 5: Indicate the type of vascular access used for HD in Tables 1 and 2. Depending on vascular access type distribution between the groups, include the vascular access in regression analysis and Table 4.

Author’s Response: Thank you for your consideration. The patients utilized either a central catheter or an arteriovenous fistula. While the type of vascular access is known to be associated with the patient's clinical prognosis (Yeh et al., 2019), it does not directly correlate with residual kidney function.

Reviewer’s Recommendations for R1: The type of vascular access used for hemodialysis can significantly impact serum levels of inflammatory markers. Hence, the recommendation to include the vascular access in the regression analysis remains very important.

Reviewer #3: The authors investigated the relationship between inflammatory markers and residual renal function in a cohort of 60 hemodialysis patients, of which 27 (45%) were anuric. Their findings revealed that elevated sTNFR1 levels were linked to reduced residual urine volumes, even after accounting for confounding factors.

The study is well-presented, and its conclusions are robust. Given the significance of these findings in translational research, this article warrants consideration for publication.

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Reviewer #2: No

Reviewer #3: No

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High level of soluble tumor necrosis factor receptors is associated with lower residual diuresis volume in patients on hemodialysis: An exploratory study.

PONE-D-24-26287R2

Dear Dr. Lacerda,

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.

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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,

Te-Ling Lu

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. 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.

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors addressed and clarified all suggestions. In particular, they clarified that all patients included in this analysis had a AVF as their vascular access. I have no further suggestions.

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Reviewer #2: No

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