Membranous nephropathy in the UK Biobank

Patrick Hamilton; Kieran Blaikie; Stephen A. Roberts; Matthew Gittins; Mallory L. Downie; Sanjana Gupta; Catalin Voinescu; Durga Kanigicherla; Horia Stanescu; Robert Kleta; Paul Brenchley

doi:10.1371/journal.pone.0281795

Peer Review History

Original SubmissionJanuary 31, 2023
14 Mar 2023 Decision Letter - Ali Moustafa Shendi Mohamed, Editor PONE-D-23-02797Membranous Nephropathy in the UK BiobankPLOS ONE Dear Dr. Hamilton, 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 28 2023 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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We will update your Data Availability statement to reflect the information you provide in your cover letter. 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript. 6. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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: -It seems that the authors meant expressing different albuminuria grades in mg/mmol (rather than mg/g). Please revise the unit used and corresponding values in the text and table 3, S4, S5. -In the last line in table 6 (distance from main road "per 100 meters"), it is not clear what the figures represent. [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: I Don't Know ****** 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 did an excellent work, using the UK BioBank data to identify patients with confirmed or potential MN according to genetic predisposition. It would be great if the authors could build on their work, by following up patients with putative MN for development of antiPLA2R Ab, and full clinical picture, and see whether this can be prevented earlier or not. May be an annual check for proteinuria, eGFR and serum antiPLA2R Ab level sounds reasonable. Please consider adjusting these changes to make the manuscript more understandable to the nephrology community: 1. Please use kidney instead of renal whenever possible, as per KDIGO latest recommendation. ESKD instead of ESRD. kidney functions instead of renal function, and so forth ... 2. There is a repeated error using albuminemia instead of albuminuria in lines 173, 209, 283. 3. Line 293: there is a symbol of question mark, what is it? 4. Please consider using the KDIGO grading of proteinuria for better understand of the degree of protienuria. uACR less than 30 is normal, and not considered proteinuria at all, A1 (normal) uACR less than 30, A2 (moderately increased) uACR 30-300 mg/g, A3 (severely increased) uACR <300 mg/g and avoid using micro and macro albuminuria terms. Reviewer 2: Well written and presented. Several limitations which the authors acknowledge - small numbers, inherent bias of the UK biobank population. Important study though how to integrate this additional information into clinical practice is not clear. Reviewer 3: No major or critical comments. The article is well wrriten. The methodology is total clear with a very good number of subjects involved. The discussion is also well written with clear details. ****** 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. https://doi.org/10.1371/journal.pone.0281795.r001
Revision 1
3 Apr 2023 Author Response PLOS ONE Journal 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 Manuscript updated to reflect journals formatting guidelines. 2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. No specific ethical approval is required. The UK Biobank has approval from the North West Multi-centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB). This approval means researchers do not require separate ethical clearance and can operate under the RTB approval (there are certain exceptions to this which are set out in the Access Procedures, such as re-contact applications). This RTB approval was granted initially in 2011 and it is renewal on a 5-yearly cycle: hence UK Biobank successfully applied to renew it in 2016 and 2021. UK Biobank will in due course apply for renewal effective in 2026. These renewal applications and approvals are shown on the website. https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us/ethics Methods section updated to state: ‘Ethics statement The UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee (MREC reference 21/NW/0157) as a Research Tissue Bank (RTB) and therefore no separate ethical approval was required.’ 3. Thank you for stating in your Funding Statement: "We acknowledge funding from Kidney Research UK (KRUK) for the Stoneygate Foundation Grant JFS_IN_003_20160914 MLD was supported by the KRESCENT post-doctoral fellowship from the Kidney Foundation of Canada" 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. Acknowledgements section updated to state: ‘Acknowledgements/Funding statement This was an approved study (I.D. 1618) by UK Biobank (http:/ukbiobank.org). We acknowledge funding from Kidney Research UK (KRUK) for the Stoneygate Foundation Grant JFS_IN_003_20160914 MLD was supported by the KRESCENT post-doctoral fellowship from the Kidney Foundation of Canada There was no additional external funding received for this study’ 4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. All data is from the UK biobank and therefore not permitted to be shared publicly. However, the data can be accessed by applying directly to the UK Biobank by any researcher worldwide through its standard application process - https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access Methods section updated to state: ‘Data availability statement All data used in this study has been obtained from the UK Biobank and due to legal constraints, the data is not permitted to be shared. All data can be accessed from UK Biobank through its standard application process’ 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript. Ethics statement included in Methods section 6. 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. References reviewed. Additional Editor Comments: -It seems that the authors meant expressing different albuminuria grades in mg/mmol (rather than mg/g). Please revise the unit used and corresponding values in the text and table 3, S4, S5. Many thanks, we have updated the text and tables accordingly. -In the last line in table 6 (distance from main road "per 100 meters"), it is not clear what the figures represent. This represents the distance from Home to the main road (manuscript now updated to state this). Reviewer 1: The authors did an excellent work, using the UK BioBank data to identify patients with confirmed or potential MN according to genetic predisposition. It would be great if the authors could build on their work, by following up patients with putative MN for development of antiPLA2R Ab, and full clinical picture, and see whether this can be prevented earlier or not. May be an annual check for proteinuria, eGFR and serum antiPLA2R Ab level sounds reasonable. Please consider adjusting these changes to make the manuscript more understandable to the nephrology community: 1. Please use kidney instead of renal whenever possible, as per KDIGO latest recommendation. ESKD instead of ESRD. kidney functions instead of renal function, and so forth ... Many thanks for this, we have now updated the manuscript with renal changed to kidney in all instances, and ESRD changed to ESKD. 2. There is a repeated error using albuminemia instead of albuminuria in lines 173, 209, 283. Again, many thanks for identifying this error, all instances have now been changed to albuminuria. 3. Line 293: there is a symbol of question mark, what is it? Many thanks for identifying this, the ‘?’ is actually ‘�’ and the manuscript has now been updated to reflect this. 4. Please consider using the KDIGO grading of proteinuria for better understand of the degree of proteinuria. uACR less than 30 is normal, and not considered proteinuria at all, A1 (normal) uACR less than 30, A2 (moderately increased) uACR 30-300 mg/g, A3 (severely increased) uACR <300 mg/g and avoid using micro and macro albuminuria terms. We have also updated the manuscript to reflect this as well. Many thanks. https://doi.org/10.1371/journal.pone.0281795.r002
10 Apr 2023 Decision Letter - Ali Moustafa Shendi Mohamed, Editor Membranous Nephropathy in the UK Biobank PONE-D-23-02797R1 Dear Dr. Hamilton, 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, Ali M Shendi Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0281795.r003
Formally Accepted
19 Apr 2023 Acceptance Letter - Ali Moustafa Shendi Mohamed, Editor PONE-D-23-02797R1 Membranous Nephropathy in the UK Biobank Dear Dr. Hamilton: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Ali Moustafa Shendi Mohamed Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0281795.r004

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