Renal hyperfiltration as a risk factor for chronic kidney disease: A health checkup cohort study

Se Won Oh; Ji Hyun Yang; Myung-Gyu Kim; Won Yong Cho; Sang Kyung Jo

doi:10.1371/journal.pone.0238177

Peer Review History

Original SubmissionMay 14, 2020
1 Jun 2020 Decision Letter - Tatsuo Shimosawa, Editor PONE-D-20-14418 Renal hyperfiltration as a risk factor for chronic kidney disease PLOS ONE Dear Dr. Jo, 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 Jul 16 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, Tatsuo Shimosawa, M.D., Ph.D. 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. Please address the following: - Please refer to any post-hoc corrections to correct for multiple comparisons during your statistical analyses. If these were not performed please justify the reasons. Please refer to our statistical reporting guidelines for assistance (https://journals.plos.org/plosone/s/submission-guidelines.#loc-statistical-reporting). - Please provide the dates upon which the patient data was accessed. - Please provide a participant flowchart. 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf 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 amend either the title on the online submission form (via Edit Submission) or the title in the manuscript so that they are identical. 6. 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 Additional Editor Comments (if provided): Two reviewers and I have concern on muscle mass differences and diverse clinical background in cohort. The authors should analyze confounding factors that affect eGFR more in details. [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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 ****** 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 ****** 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 paper presents a retrospective analysis of health examination data from healthy adults and shows that RHF is a risk factor for proteinuria and decline of eGFR, and suggests that increased monocyte count may be a predictor of CKD progression. In CKD, which often follows an irreversible progression, it is "paramount" to recognize patients at a very early stage as preliminary CKD patients, as described by the authors, and the results of this study will make a significant contribution to future CKD treatment. The points I noticed were as follows; (1) Was there any difference in the data between the RHF group with a BMI＞30 and the RHF group with a BMI＜20? (2) It has been shown in Table 2 that RHF seems to be involved in the progression of proteinuria and reduction of eGFR after adjusting for risk such as diabetes, but if the authors analyzed the RHF population excluding diabetes, what would be the differences in characteristics between the no RHF population? (3) In the first paragraph of the introduction, line 11, the word "Monocyte" seemed to appear out of the blue. Wouldn't it be better to break a new line or put a preposition of some kind? (4) On page 13, line 3, RFH should be corrected to RHF. (5) On page 13, line 4, “this is a first study” → “this is the first study”？ Reviewer #2: Overall impression; The subject is interesting, but the authors should show the conclusive and convincing evidence demonstrating that RHF per se is a risk factor for CKD. Major criticisms; 1) The RHF group has statistically significantly more eGFR and less BUN. This suggests that the muscle mass in the RHF group might be less. This is supported by the statistically different distributions of BMI in the two groups, i.e. there are more patients with BMI less than 20 in the RHF group. If this is correct, the high eGFR doesn't simply indicate renal hyperfiltration. 2) There are statistically significantly more patients who have hypertension (>130 mmHg), proteinuria and DM in the RHF group than those in the non-RHF group. More patients with CKD risk factors in the RHF group can explain the higher susceptibility of CKD progression. 3) The higher high-sensitivity C-reactive protein was already shown to be the risk factor of CKD progression. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090815/)(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133564/) (https://www.sciencedirect.com/science/article/abs/pii/S0002870319301723) The higher monocyte count in peripheral blood was already shown to be the risk factor of CKD progression. So what is novel in this manuscript is the higher susceptibility of CKD progression with higher monocyte count and higher CRP levels in the RHF group, but we cannot tell if the higher susceptibility of CKD progression in the RHF group is explained by the RHF per se or higher prevalence of hypertension and DM etc in the RHF group. ****** 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 [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.0238177.r001
Revision 1
19 Jul 2020 Author Response Dear reviewers Thank you for your thoughtful comments regarding our manuscript. We took your comments seriously and revised our manuscript. Review Comments to the Author Reviewer #1: This paper presents a retrospective analysis of health examination data from healthy adults and shows that RHF is a risk factor for proteinuria and decline of eGFR, and suggests that increased monocyte count may be a predictor of CKD progression. In CKD, which often follows an irreversible progression, it is "paramount" to recognize patients at a very early stage as preliminary CKD patients, as described by the authors, and the results of this study will make a significant contribution to future CKD treatment. The points I noticed were as follows; Was there any difference in the data between the RHF group with a BMI＞30 and the RHF group with a BMI＜20? Thank you for your comment. We re-analyzed the data about the renal function decline and RHF group stratified by BMI. The incidence of 30% eGFR decline was significantly higher in RHF group with a BMI <20 kg/m2 (10.0% vs. 0.1%, P<0.001) and ≥30 kg/m2 (6.2% vs. 0.4%, P=0.003). In multivariate analysis, RHF was an independent risk factor for 30% eGFR decline in participants with both BMI <20 kg/m2 and ≥30 kg/m2 (P≤0.024). We agree with your concern that creatinine based eGFR could lead to overestimation of eGFR in participants with lower muscle mass such as BMI <20 kg/m2, resulting in falsely categorized as RHF. So, we compared the percent lean body mass between RHF vs no RHF group in a given range of BMI. We noticed that percent lean body mass was not different between RHF group and no RHF group in participants with BMI <20 kg/m2 (supplement table 1). These data can support that reduced muscle mass does not account for elevated eGFR in these groups. Interestingly, we observed that percent body fat body fat was significantly higher (P≤0.032), while percent lean body mass was significantly lower (P≤0.034) in RHF group compared to no RHF group (supplement table 1). These data can suggest that RHF and further decline of eGFR in these participants might be related to obesity or obesity related inflammation. We added these data as supplemental table 1 and also in discussion section. It has been shown in Table 2 that RHF seems to be involved in the progression of proteinuria and reduction of eGFR after adjusting for risk such as diabetes, but if the authors analyzed the RHF population excluding diabetes, what would be the differences in characteristics between the no RHF population? Thank you for indicating the very important aspect of our data. According to your suggestion, we reanalyzed the data excluding patients with diabetes and found that even after excluding diabetes, eGFR decline was also significantly higher in RHF group than no RHF group (0.4 % vs. 8.4%, P<0.001). After adjusting risk factors, RHF was found to be an independent risk factor for the progression of eGFR 30% decline (RR, 7.123, 95% CI, 3.314-15.310) in non diabetic participants. However, incident proteinuria was not associated with RHF if we exclude patients with diabetes. Currently, we do not know exactly why there is a discrepancy. The possible explanation might be related to definition of proteinuria by dipstick test that is less accurate than quantitative measurement of albumin or protein. Another possibility is that proteinuria by dipstick test detects only albumin and CKD progression from non diabetic etiologies, characterized by interstitial inflammation and fibrosis might not be related to the development or progression of albuminuria. We added the new data in the results section and also possible explanation in the discussion section. In the first paragraph of the introduction, line 11, the word "Monocyte" seemed to appear out of the blue. Wouldn't it be better to break a new line or put a preposition of some kind? I added following sentences before the word “monocyte”: Inflammation plays an important role in the loss of renal function in CKD. On page 13, line 3, RFH should be corrected to RHF. Thank you for your correction. (5) On page 13, line 4, “this is a first study” → “this is the first study”？ Thank you for your correction. Reviewer #2: Overall impression; The subject is interesting, but the authors should show the conclusive and convincing evidence demonstrating that RHF per se is a risk factor for CKD. Major criticisms; The RHF group has statistically significantly more eGFR and less BUN. This suggests that the muscle mass in the RHF group might be less. This is supported by the statistically different distributions of BMI in the two groups, i.e. there are more patients with BMI less than 20 in the RHF group. If this is correct, the high eGFR doesn't simply indicate renal hyperfiltration. Thank you for your comment We agree with your concern that creatinine based eGFR could lead to overestimation of eGFR in participants with lower muscle mass such as BMI <20 kg/m2, resulting in falsely categorized as RHF. So, we compared the percent lean body mass between RHF vs no RHF group in a given range of BMI. We noticed that percent lean body mass was not different between RHF group and no RHF group in participants with BMI <20 kg/m2 (supplement table 1). These data can support that reduced muscle mass does not account for elevated eGFR in these groups. Interestingly, we observed in participants with BMI≥20 kg/m2, that percent body fat body fat was significantly higher (P≤0.032), while percent lean body mass was significantly lower (P≤0.034) in RHF group compared to no RHF group (supplement table 1). These data can suggest that RHF and further decline of eGFR in these participants might be related to obesity or obesity related inflammation. We added these data as supplemental table 1 and also in discussion section There are statistically significantly more patients who have hypertension (>130 mmHg), proteinuria and DM in the RHF group than those in the non-RHF group. More patients with CKD risk factors in the RHF group can explain the higher susceptibility of CKD progression. Thank you for your comments and we re-evaluated the eGFR decline in RHF group after excluding the participants with SBP >130 mmHg, proteinuria at baseline, or diabetes (N=39,781). Decline of 30% eGFR was significantly higher in RHF group than no RHF group (0.3% vs. 8.9%, P<0.001). In multivariate analysis, RHF was found to have 4.913-fold increase for the decline in 30% eGFR (95% CI, 1.959-12.320) compared to no RHF group. These data strongly suggest that RHF per se represent a very early stage of CKD and decline of eGFR is not caused by underlying diabetes, hypertension or underlying CKD. We added these data as supplemental table 2 and also in the discussion section. 3) The higher high-sensitivity C-reactive protein was already shown to be the risk factor of CKD progression. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090815/)(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133564/) (https://www.sciencedirect.com/science/article/abs/pii/S0002870319301723) The higher monocyte count in peripheral blood was already shown to be the risk factor of CKD progression. So what is novel in this manuscript is the higher susceptibility of CKD progression with higher monocyte count and higher CRP levels in the RHF group, but we cannot tell if the higher susceptibility of CKD progression in the RHF group is explained by the RHF per se or higher prevalence of hypertension and DM etc in the RHF group. Thank you for your critiques As you pointed out, higher monocyte count has been demonstrated to be a risk factor of CKD progression by Bowe et.al. in CJASN 2017 Apr 3; 12(4): 603–613. The population in that study consisted of predominantly white male (while 83%, male 97.9%) with significantly higher prevalence of diabetes (28.6%), hypertension (68.2%) with mean eGFR of 76.3. In contrast, we analyzed apparently healthy population undergoing regular health check ups with significantly lower prevalence of diabetes or hypertension, significantly higher eGFR (86.5±13.7, 126.5±14.1; no RHF, RHF). And according to your comments, we excluded patients with diabetes, hypertension and baseline proteinuria, and still found that RHF had 4.913-fold increase for the decline in 30%eGFR (95% CI, 1.959-12.320) compared to no RHF group, indicating that RHF per se is a risk factor of CKD. We also observed that monocyte count could predict the development of 30% decline of eGFR in participants with RHF even after excluding HTN, DM, and proteinuria. The 2nd tertile and the 3rd tertile of monocyte in the RHF group showed 9.110-fold and 5.336-fold increased risk of 30% eGFR decline (95% CI; 2.918-28.447 in the 2nd tertile;; 95% CI: 1.551-18.358in the 3rd tertile) (supplement table 2). So, we suggest that 1) RHF per se represent a very early stage of CKD and 2) increased monocyte count can be a marker of progressive CKD in healthy population with RHF. We added this points in the discussion section. Thank you for your consideration. Sincerely, Sang Kyung Jo, MD, PhD Professor Division of Nephrology, Department of Internal Medicine, Korea University Medical College Address : Korea University Anam Hospital, Koreadae-Ro 73, Sungbuk-Gu Seoul, Republic of Korea 02841 e-mail : sang-kyung@korea.ac.kr Attachments Attachment Submitted filename: respose_reviewers_0715.docx https://doi.org/10.1371/journal.pone.0238177.r002
31 Jul 2020 Decision Letter - Tatsuo Shimosawa, Editor PONE-D-20-14418R1 Renal hyperfiltration as a risk factor for chronic kidney disease: A health checkup cohort study PLOS ONE Dear Dr. Jo, 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 clarify if Figure 2 is mislabeled. Please submit your revised manuscript by Sep 14 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, Tatsuo Shimosawa, M.D., Ph.D. Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] 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 ******** 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: Yes 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: The previous reviewer's comments have been adequately addressed and improvements in content have been recognized. (1) Figure 1 attached to the manuscript, which is divided into Figure 1 A-D, is described in the text as Figure 2 A-D, and there is no Figure 1 appended to the "Materials and Methods, Participants" section. (2) Similarly, Figure 2, which is attached to the manuscript, is shown as Figure 3 in the text (page 10, line 7). (3) Figure legends is similarly described as Figure 1 and 2, which is not consistent with Figure 1-3 in the manuscript. From the text, it looks like a new Figure 1 has been added, and if so, I'd like to check that Figure. Reviewer #2: You answered all the questions asked at the first submission and corrected the manuscript with proper supplemental information. ****** 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. https://doi.org/10.1371/journal.pone.0238177.r003
Revision 2
9 Aug 2020 Author Response Dear reviewers Thank you for your thoughtful comments regarding our manuscript. We took your comments seriously and revised our manuscript again. Reviewer #1: The previous reviewer's comments have been adequately addressed and improvements in content have been recognized. (1) Figure 1 attached to the manuscript, which is divided into Figure 1 A-D, is described in the text as Figure 2 A-D, and there is no Figure 1 appended to the "Materials and Methods, Participants" section. Thank you for your correction. (2) Similarly, Figure 2, which is attached to the manuscript, is shown as Figure 3 in the text (page 10, line 7). Thank you for your correction. (3) Figure legends is similarly described as Figure 1 and 2, which is not consistent with Figure 1-3 in the manuscript. Thank you for your correction. From the text, it looks like a new Figure 1 has been added, and if so, I'd like to check that Figure. Reviewer #2: You answered all the questions asked at the first submission and corrected the manuscript with proper supplemental information. Thank you for your consideration. Sincerely, Sang Kyung Jo, MD, PhD Professor Division of Nephrology, Department of Internal Medicine, Korea University Medical College Address : Korea University Anam Hospital, Koreadae-Ro 73, Sungbuk-Gu Seoul, Republic of Korea 02841 e-mail : sang-kyung@korea.ac.kr Attachments Attachment Submitted filename: response_reveiwers_0809.docx https://doi.org/10.1371/journal.pone.0238177.r004
12 Aug 2020 Decision Letter - Tatsuo Shimosawa, Editor Renal hyperfiltration as a risk factor for chronic kidney disease: A health checkup cohort study PONE-D-20-14418R2 Dear Dr. Jo, 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, Tatsuo Shimosawa, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0238177.r005
Formally Accepted
26 Aug 2020 Acceptance Letter - Tatsuo Shimosawa, Editor PONE-D-20-14418R2 Renal hyperfiltration as a risk factor for chronic kidney disease: A health checkup cohort study Dear Dr. Jo: 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 Prof. Tatsuo Shimosawa Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0238177.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .