PONE-D-21-31746Weight Gain After Renal Transplant: Prevalence, Risk Factors, and OutcomesPLOS ONE

Dear Dr. Altheaby,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

John Richard Lee, M.D.

Academic Editor

PLOS ONE

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

Additional Editor Comments;

In addition to the reviewers’ comments, please consider the following:

1) It’s unclear to me that weight gain was observed in 235 patients and weight decreased in 57 patients but Table 1 shows gained weight (n=161) and stable weight (n=134).

2). How did the authors choose a BMI >2 as a cutoff? Do the authors have literature support this cutoff?

3) Table 1 should have legend explaining the test comparing the two groups (i.e. Fisher’s exact test and/or unpaired t-test). Also Table 2 and Table 3.

4) What were the maintenance immunosuppression in each group? This data should be included. Was the weight gain driven by prednisone? Are differences in other regimens?

5) Is the repeated measured analysis with contrasts? Can you please explain more detail in the methods how this was done since you are comparing groups at different time points?

6) How did you define proteinuria? Did you quantify the proteinuria with a Urine P/C ratio?

7) More detail is needed in Table 3: how did you define rejection, DGF, CMV, and BK? How long was the follow up for patients, was this all at 1 year?

8) In the multivariable logistic regression, how did you choose the variables that went into the multivariable analysis? Did you do a univariate analysis and those significant went into the multivariable analysis? How did you come to choose age > 40 rather than continuous variable?

9). The authors note mortalities? Did this occur in the first year? If so, how was the weight account for if the patient died before 1 year?

10) Figure 1 and Figure 2 need legends and should be separated

11) The manuscript would benefit from grammatically editing

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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: No

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

Reviewer #1: I Don't Know

Reviewer #2: No

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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: No

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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: This is a single center retrospective cohort study of 295 kidney transplant recipients in Saudi Arabia whose objective is to estimate the prevalence of weight gain in the first-year post kidney transplantation, identify potential risk factors, and assess allograft outcomes. The authors observe weight gain in nearly 80% of patients, with patients with lower dialysis duration having significantly higher risk of weight gain. Graft outcomes were comparable in both the “stable weight” and “gained weight” groups. As noted by the authors, a limitation is the short follow up period for potential complications.

Overall, the authors’ findings will be beneficial to the field, adding to data regarding the prevalence and significance of weight gain post renal transplantation, particularly in a population from Saudi Arabia that has not been well studied. The manuscript is organized and written reasonably well. However, it requires careful review and proofreading of grammatical and typographical errors. My recommendations include the following:

1. The authors report that patients “had the same tacrolimus-based maintenance immunosuppression regimen”. It would be useful to clarify if patients are on steroid-free or steroid maintenance immunosuppression and report if there are differences in steroid use between the groups.

2. Abbreviations and acronyms such as CMV, BK, DM, FBS should be spelled out in full the first time they are used, and the standard abbreviation provided in parentheses.

3. In the Results section there is mention of 57 patients having decreased weight. Were these patients categorized under the “stable weight” group?

4. In Table 1, please report units of measurement for “Duration of dialysis” (e.g. months or years).

5. In Figures 1 and 2, please report units of measurement for blood pressure. In Figure 2, please label the two groups appropriately by adding “BMI” to “<2” and “>=2”.

6. In Table 2, please clarify criteria for “proteinuria”.

7. In Table 2, “FBS” is reported as mg/dL, however the values provided appear to be consistent with mmol/L.

8. In Table 3, please define “BK”. For instance, is this referring to BKV nephropathy, BKV viremia or BKV viruria?

9. The authors report CMV infection was significantly less common in the group that gained more weight, and they could not find an explanation for this finding. However, they do not discuss any further analysis that may have been done. It may be useful to explore variables such as CMV serostatus of the donor/recipient pair, CMV prophylaxis regimen, and donor type (there was a trend toward more deceased donors in the "stable weight" group).

10. There are numerous typographical and grammatical errors throughout the manuscript. Recommend a meticulous review and proofreading of the manuscript.

Thank you for the opportunity to review this manuscript.

Reviewer #2: 1. In methods, clarify "Comparison between groups was assessed by unpaired t-test or Mann-Whitney test while

follow-up data were compared using paired t-test and repeated measures ANOVA". what does groups and follow up data refer to? Also, express age as median and interquartile range since it is a skewed distribution.

2. The induction therapy in about 60% was ATG, what was the regimen in the remaining? What is the tacrolimus based regimen- does it include steroids? Need to clarify the immunosuppresive regimen

3. Many descriptions used in the table is ambiguous- what does "bariatric" refer to? What is the unit used to express duration of dialysis. What does DM, HTN and CAD stand for. Similarly table 2 also needed to be revised to correct for incomplete descriptions and units. What was the definition of CMV infection used for the manuscript?

4. Many abbreviations are used throughout the manuscript without mentioning their expansion in the manuscript.

5. Since the authors have not rigorously studied if the outcomes were directly related only to the weight gained post transplant and it is a retrospective study, it is not appropriate to use the term "outcomes" in the title and conclusion

6. Since the authors looked at weight gain post transplantation, it is looking at incidence rather than prevalence of weight gain

7. The manuscript needs to rigorously reviewed again for several grammatical errors and poor sentence construction

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

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Reviewer #1: No

Reviewer #2: No

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PONE-D-21-31746R1Weight Gain After Renal Transplant: incidence, Risk Factors, and OutcomesPLOS ONE

Dear Dr. Altheaby,

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 Apr 03 2022 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,

John Richard Lee, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

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.

Additional Editor Comments:

Please address comments of the reviewer.

1) Also please put the details in the methods/results on what was done specifically for the anova testing, as described in the response letter.

2) Also please put the details in the methods/results on what was done specifically for the multivariable logistic regression, as described in the response letter.

3) The manuscript needs thorough editing for fluency and grammar as also indicated by Reviewer 1.

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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)

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: I Don't Know

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 #1: Yes

Reviewer #2: 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

Reviewer #2: 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: Thank you for the revisions and helpful clarifications.

1. There are several typographical errors throughout the manuscript. Again, recommend a thorough review and editing of grammatical errors. For instance, in the Abstract under “Objective”, the sentence should likely read, “The objective of this study is to estimate…”

2. In the multivariate analysis (Table 4), it may be helpful to state why and how age >40 was chosen as a variable.

3. For Figures 1 and 2, please add units of measurement for blood pressure.

Thank you for the opportunity to review this manuscript.

Reviewer #2: (No Response)

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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: No

Reviewer #2: No

[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.

Weight Gain After Renal Transplant: incidence, Risk Factors, and Outcomes

PONE-D-21-31746R2

Dear Dr. Altheaby,

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,

John Richard Lee, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: