Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

PONE-D-20-30112

Sex Differences in Chronic Kidney Disease Awareness among US Adults, 1999 to 2018

PLOS ONE

Dear Dr. Schernhammer,

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 Dec 04 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Florian Kronenberg

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. Thank you for stating in your Funding Statement:

"Initials of the authors who received each award: MH

Grant numbers awarded to each author: KL754-B

The full name of each funder: FWF, Austrian Science Fund

URL of each funder website: https://m.fwf.ac.at/en/

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

4. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data.

5. Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately.  These will be automatically included in the reviewers’ PDF.

6. 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.

7. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

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 **.

[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?

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

Reviewer #3: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: N/A

**********

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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: The authors examine NHANES data to conclude that CKD awareness is lower in women than in men and that the gap between the sexes is narrowing due to greater reliance on eGFR, replacing serum creatinine, as a measure of renal function

Major

1. NHANES does not provide data regarding access to healthcare. There are no data to assess the frequency which women versus men visit PCPs or are referred for consultation to a nephrologist. Prior publications indicate that women are referred to nephrologists less frequently than men and data from the USRDS suggests that women undergo fewer serum creatinine measurements than men. Less contact with PCPs and nephrologists and fewer serum creatinine measurements may contribute to lesser awareness of CKD. The authors should include this limitation in their discussion.

Minor

1. The authors point to a large body of literature that indicates that CKD is less prevalent in men than in women. In this context, they should discuss limitations of these data including (1) differences in bias between the sexes in the GFR estimating equations and (2) controversy regarding the need for sex/age specific GFR cut offs and UACR cutoffs to define CKD.

2. In the Introduction section the authors point out that women start dialysis at a lower GFR than men. However they should also point out that this observation does not account for the difference in bias between the sexes in the GFR estimating equations which is equivalent to the difference in the GFR at the start of dialysis in men vs. women.

3. The authors indicate that serum creatinine was corrected and cite several references -- NHANES Data Documentation, Codebook, and Frequencies. Since standardization of creatinine assays is an important issue in evaluating their data and conclusions, the authors should describe in some detail how the correction was performed.

4. The authors may wish to speculate as to why it is that Caucasian women drive the increase in CKD awareness over time.

5. The authors may wish to point out the weakness of data from the USRDS that seem to contradict their conclusions. USRDS data show that women are as likely as men to receive pre-ESRD care from a nephrologist, strongly suggesting equivalent CKD awareness in men and women in late stage CKD. However, these data are seriously limited since they only apply to individuals who ultimately start dialysis

6. In general the paper is clear, well written and easy to understand. However, on several occasions the authors misuse idioms that obfuscate the meaning of sentences. For example: “consecutively declining” and “tilt towards”. (Unfortunately the pages are not numbered so I cannot identify these phrases by page and line number).

Reviewer #2: Hödlmoser et al. investigated the sex difference in the awareness of CKD using data from US NHANES. Overall, the awareness was low <22.5%. The authors observed higher awareness in men than in women, but the sex-difference became smaller overtime. The sex difference was more evident in whites than in blacks. The study question is important and the manuscript is well written overall. Nonetheless, I have several suggestions and comments as summarized below.

Major

1. The definition of CKD.

a. “CKD is characterized by a gradual loss of kidney function,” Kidney damage is a part of CKD, which may not be accompanied by reduced kidney function. This sentence thus should be rephrased.

b. “we restricted our study to CKD stages 3 to 5, which are based solely on eGFR” Please specify that these are KDIGO CKD G stages. This comment applies to the entire manuscript.

c.

2. Not sure whether the authors reported weighted results for the descriptive statistics in the section of “Characteristics of the study sample”. Please specify. If the authors reported unweighted estimates, they should report the weighted results instead.

3. Figure 2 was blank in the PDF.

4. Figure 2 may be trying to show this, but it seems important to show an analysis restricted to participants with diabetes, hypertension, or both.

Minor

Abstract

1. Please specify that sampling weights were taken into account in the Abstract.

Methods

2. “[20 to 50 years], [50 to 65 years], [65 to 80 years] and 80+ years” Not clear which category included 50, 65, and 80 years old.

Results

3. “most of the study participants (92.7%) had CKD stage 3” This seems misleading. I believe the authors meant “most of the study participants with CKD had G stage 3”

4. “Due to the low number of participants with CKD stage 5, the volatility and decrease of awareness in both sexes should be considered with caution.” This is not a result and thus should be moved to Discussion.

5. “Figure 4 s” s should not be in bold.

Discussion

6. The authors should discuss higher awareness in blacks than in whites.

7. “Chronic kidney disease is defined by abnormalities of kidney function,” The defined abbreviation of CKD should be used.

Reviewer #3: The review is too difficult to read. The main problem is due to a different diseases that can lead to CKD. For example the glomerulonephrithis should be considered. Also CKD should be diagnosed also considered urine output, proteinuria, ecc

**********

6. 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

Reviewer #3: 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.

Sex Differences in Chronic Kidney Disease Awareness among US Adults, 1999 to 2018

PONE-D-20-30112R1

Dear Dr. Schernhammer,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Florian Kronenberg

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

Reviewer #2: All comments have been addressed

**********

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: (No Response)

Reviewer #2: Yes

**********

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

Reviewer #1: (No Response)

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: (No Response)

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: (No Response)

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: (No Response)

Reviewer #2: Overall, the authors have adequately addressed my comments. I do not have any other additional comments.

**********

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