PONE-D-24-04086Sarcopenic obesity in predialysis chronic kidney disease: muscle strength is a predictor of mortality and disease progression in a six-year prospective cohortPLOS ONE

Dear Dr. Souza,

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.

 Both reviewers found merit in your manuscript but clarification on several points are needed. Some statements will need to be referenced and please provide the rationale for why certain criteria was selected. This was brought up by one of the reviewers, so please make sure that is addressed not only in the rebuttal but also in the manuscript.

Please submit your revised manuscript by Nov 09 2024 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.

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Jeremy P Loenneke

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

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: Partly

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

Reviewer #1: Yes

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: Yes

Reviewer #2: Yes

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4. 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 #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: Excellent manuscript and fine publication on this complicated topic.

Abstract

Include low and moderate BMI and death results.

Methods

Define kg/f

Discussion

The results from table 6 ie. BMI 18.5-24.9 and BMI < 18.5 should be discussed. These data suggest that low and moderate BMI is a cause for concern as is low grip strength.

Reviewer #2: This study aims to assess the associations of predialysis CKD patients with sarcopenic obesity and its components with death and disease progression to renal replacement therapy. This is an important topic and the information gained has the potential to positively benefit both patients with CKD and clinicians.

However, there are several concerns that need to be addressed by the authors.

Lines 58-59: reference is needed.

Lines 69-71: “The main findings regarding SO in patients with CKD are a direct relationship with albuminuria, even in patients with normal BMI”. I was not able to locate the reference in which SO was directly related to CKD patients with normal BMI. Please include. Also, by definition, individuals with a normal BMI are not obese. Therefore, is it possible to have sarcopenic obesity if you have normal BMI?

Ensure all abbreviations used consistently throughout the manuscript and are defined at first use. For example, FNIH and EWGSOP are not define within the text.

Line 104: decimal places should be consistent

Methods:

No rationale is provided for why both the EWGSOP and FNIH criteria were used. Also, only the FNIH criteria was used to assess SO and for analysis. Please provide clarification as to why EWGSOP was included in the methodology or why it was not used to assess SO and included in the analysis.

Participants were recruited from 2014-2022. The first phase of the study consisted of a cross-sectional evaluation of patients carried out between 2014-2016 which also included 100 participants (lines 90-93). Therefore, it seems no additional participant were recruited from 2017-2022, is this accurate? Please also include how many participants were excluded during the enrollment period and the reasons why such participants did not meet inclusion criteria.

Lines 123-125: “FNIH criteria were used in combination with BMI, FMI, and BFP to assess SO”. It is not clear how SO was diagnosed. What specific variables were used? And if multiple body composition variables were used as indicated, how did this change the prevalence of SO based on the variable used? Also, is there precedent for the method used in this study? If so, please include reference.

Please expand upon methods for how grip strength and gait speed were measured. For example, was grip strength determined in the dominant limb or both limbs. Were participants in the seated or standing position? Where participants instructed to walk at their customary gait speed?

Statistical analysis:

Lines 151-153: “associations were analyzed with Pearson correlation coefficient.” This information does not seem to be presented in the manuscript.

Results:

Lines 162-163: “Obesity was present in 36%, 28% of the sample had sarcopenia, and 16% had SO”. Please consider editing this sentence for clarity.

Table 4: authors indicate triglycerides to be significantly different between groups at a p-value of 0.054. This does not meet the level of significance as proposed in the statistical analyses section (p-value < 0.05).

Figure 1 quality makes it difficult to read and interpret.

Its unclear what added information Tables 5 and 6, please consider removing.

Lines 197-199: please include abdominal circumference values in Table 1 if measured.

Were differences in body composition and FNIH outcomes assess between SO and non-SO groups? This information is not presented in the Results.

Discussion:

Lines 211-212: “Higher levels of IL-6 were found in the SO group than non-SO group”. This statement does not seem to be true given that there were no significant differs between groups in IL-6 according to Table 4 or lines 168-170. Please revise.

Lines 212-216: Have the authors given consideration to the differences between primary (aging) versus secondary (disease-induced) sarcopenia and how this might influence the interpretation of the findings?

Lines 218-220: again, the data do not seem to support this statement. Please revise.

Lines 224-226: “greater risk of mortality in patients with lower BMI”. This statement deserves greater attention and discussion regarding the obesity paradox seems warranted.

Lines 234-244: this paragraph seems to lump together myosteatosis and strength. Although there is the potential for some interaction between these concepts, they are distinct from one another.

What are the clinical implications of the findings of this work? Given the importance of strength, what interventions should be considered? Has resistance exercise been shown to beneficial for preserving muscle health and strength in CKD patients?

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Reviewer #1: Yes:  Charles Paul Lambert, PhD

Reviewer #2: Yes:  Jared M. Gollie

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PONE-D-24-04086R1Sarcopenic obesity in predialysis chronic kidney disease: Muscle strength is a predictor of mortality and disease progression in a six-year prospective cohortPLOS ONE

Dear Dr. Souza,

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.

 The reviewer thought you addressed most of the concerns, however, there are a few that remain (labeling of tables, and a bit more discussion) which is why I rendered the decision of "minor revision".

Please submit your revised manuscript by Jan 30 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,

Jeremy P Loenneke

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 #1: (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 #1: Yes

**********

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

Reviewer #1: 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 #1: 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 #1: Yes

**********

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 #1: A well done project examining the effects of Sarcopenic obesity on a number of variables. Of note it appears that the heading for Non SO and Sarcopenic Obesity are switched for this table 3. This is evident when one looks at the significant measurements near the bottom of the table. For a discussion of table 6. The authors should discuss other papers where moderate to low bmi is associated with increased risk or rate of death. Additionally, providing evidence or explanation as to why grip strength predicts time to death is warranted. Things such as physical activity, nutrition, and rest or sleep!

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). 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 Privacy Policy .

Reviewer #1: Yes:  Charles Paul Lambert, PhD

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[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.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Sarcopenic obesity in predialysis chronic kidney disease: Muscle strength is a predictor of mortality and disease progression in a six-year prospective cohort

PONE-D-24-04086R2

Dear Dr. Souza,

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,

Jeremy P Loenneke

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 #1: 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 #1: Yes

**********

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

Reviewer #1: 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 #1: Yes

**********

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 #1: Yes

**********

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 #1: Well done. Excellent manuscript which advances the Sarcopenic obesity field. The authors should parlay this into major funding as this was an unfunded study. The problem of fat and low muscle mass is primarily a problem of a sedentary lifestyle. Regular resistance training and aerobic training can add muscle mass and reduce weight, respectively.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). 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 Privacy Policy .

Reviewer #1: Yes:  Charles Paul Lambert, PhD

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