Mortality and evolution between community and hospital-acquired COVID-AKI

Jonathan S. Chávez-Íñiguez; José H. Cano-Cervantes; Pablo Maggiani-Aguilera; Natashia Lavelle-Góngora; Josué Marcial-Meza; Estefanía P. Camacho-Murillo; Cynthia Moreno-González; Jarumi A. Tanaka-Gutiérrez; Ana P. Villa Zaragoza; Karla E. Rincón-Souza; Sandra Muñoz-López; Olivia Montoya-Montoya; Guillermo Navarro-Blackaller; Aczel Sánchez-Cedillo; Luis E. Morales-Buenrostro; Guillermo García-García

doi:10.1371/journal.pone.0257619

Peer Review History

Original SubmissionApril 9, 2021
11 Jun 2021 Decision Letter - Boris Bikbov, Editor PONE-D-21-11844 Mortality and evolution between Community and Hospital-acquired COVID-AKI PLOS ONE Dear Dr. Chávez-Iñiguez, 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. As the Academic Editor, I have sent your manuscript for revision to several persons. Currently one expert in the field has already provided the peer-review with a very detailed and useful comments, suggesting Major Revision. Other experts invited so far have declined the invitation to review the manuscript (it is rather widespread situation, related to different factors). I would like to save your time, and provide the possibility to perform the revision of the manuscript based on the feedback from one expert in the field, and make it stronger. Once you submit the revised manuscript, I will send it to the expert who provided the feedback, and also involve another reviewer. If you have any objections for this approach, please let me know. If you agree, please proceed this way and submit the revised manuscript along with the point-by-point responses to the reviewer. Please submit your revised manuscript by Jul 26 2021 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. 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, Boris Bikbov 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 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. 3. Thank you for providing the date(s) when patient medical information was initially recorded. Please also include the date(s) on which your research team accessed the databases/records to obtain the retrospective data used in your study 4.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. Additional Editor Comments (if provided): [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 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 ****** 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 ****** 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 an interesting retrospective study highlighting the differences between HA AKI and CA AKI in COVID patients. The findings are in contrast to that of literature where HA AKI due to usual causes have been found to have worse outcome due to the number of comorbidities. Interestingly, the difference of > 10% in mortality between CA AKI and HA AKI did not show significance. The authors have 28-day mortality as the primary outcome. Does the table 1 show 28-day outcome as some patients may still be in-patient as we know COVID patients have longer length of stay. Do the authors have in-hospital mortality as FU after discharge may result in loss of follow up. Loss of 18.3% of study population due to loss of creatinine is surprising. Do decide about baseline creatinine, the authors have gone back a year but to get a baseline for patients who had pre-existing CKD G1-G5 not on dialysis, only previous 3 months creatinine was necessary, otherwise they were also excluded from the analysis The other observation is that patients with first admission were included. This creates a survival bias as patient may have died in subsequent admission The authors have used variable end-points. On some occasions, the authors report survival and on other occasion, mortality. The literature reports mortality for AKI. For example: The multivariable regression is using mortality as dependent variable which survival is quoted for HA & CA AKI Was AKI not defined by KDIGO classification? This is not stated in methods ****** 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: Yes:** Nitin V Kolhe [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.0257619.r001
Revision 1
25 Jun 2021 Author Response Response to Reviewers' We appreciate the time and the review process, without a doubt the comments of the editors are all relevant and pertinent, they contribute to making our manuscript stronger. We have done our best to satisfy each of them. Reviewer #1: 1.-The findings contrast with that of literature where HA AKI due to usual causes have been found to have worse outcome due to the number of comorbidities. R= We are glad that the editor has noted this point, from our perspective it is also a valuable argument in our manuscript, and we give a detailed explanation of why this result happened in page 21, 22. 2.-Interestingly, the difference of > 10% in mortality between CA AKI and HA AKI did not show significance. R= We believe that the limited number of the event could have explained the lack of statistical significance (p = 0.06), although the trend is notable. 3.- The authors have 28-day mortality as the primary outcome. Does the table 1 show 28-day outcome as some patients may still be in-patient as we know COVID patients have longer length of stay. Do the authors have in-hospital mortality as FU after discharge may result in loss of follow up. R= We understand the point, without a doubt the long-term follow-up would be relevant, but we only took into account the first 28 days of the stay in the hospital, unfortunately we could not follow the patients once they were discharged from the hospital, we faced the reality where COVID patients hardly come for follow-up. If the reviewer agree, we could add the following sentence to the limitations (page 24): Mortality was only considered during the 28 days of hospitalization and a longer follow-up would have been appropriate since many patients have prolonged hospital stays. 4.- Loss of 18.3% of study population due to loss of creatinine is surprising. R= We excluded 230 (18.3%) patients from the analysis, mainly because despite being hospitalized, they did not have serum creatinine measurement, we know the importance of this variable, but in our hospitals the systematic request of serum creatinine is not performed unless the treating physicians request it. It is probable that the overload of work and the saturation of the clinical laboratories during pandemic has contributed as well. 5.-Do decide about baseline creatinine, the authors have gone back a year but to get a baseline for patients who had pre-existing CKD G1-G5 not on dialysis, only previous 3 months creatinine was necessary, otherwise they were also excluded from the analysis R= We agree with the reviewer's comment, we only need 3 months was necessary, we will change the text of the manuscript as follows: The baseline Scr level was defined as the lowest Scr value that was available in the last 3 months prior to admission and throughout the hospital stay (page 7) 6.- The other observation is that patients with first admission were included. This creates a survival bias as patient may have died in subsequent admission R= We understand the concern of the reviewer. We decided to consider only the first hospital admission since the nature of our study was mainly to compare HA-AKI vs CA-AKI. The event of CA-AKI would not be interpreted properly if the patient who had been discharged was hospitalized again, we think that this previous hospitalization strongly contributes to her readmission, making the conditions of CA-AKI completely different. Finally we believe that readmissions were <10%. 7.- The authors have used variable end-points. On some occasions, the authors report survival and on other occasion, mortality. The literature reports mortality for AKI. For example: The multivariable regression is using mortality as dependent variable which survival is quoted for HA & CA AKI R=We appreciate the observation, we fully agree. We will change all the words surival for mortality when apropiate, you will find it on pages: 7, 8, 9, 11, 13, 14 8.- Was AKI not defined by KDIGO classification? This is not stated in methods R= In methods section (page 6) you will find the phrase where we describe the definition of AKI by KDIGO. AKI was diagnosed by the serum creatinine (Scr) KDIGO criteria (13) Attachments Attachment Submitted filename: response to reviewer 25_6_21.docx https://doi.org/10.1371/journal.pone.0257619.r002
14 Jul 2021 Decision Letter - Boris Bikbov, Editor PONE-D-21-11844R1 Mortality and evolution between Community and Hospital-acquired COVID-AKI PLOS ONE Dear Dr. Chávez-Iñiguez, 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 Aug 28 2021 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. 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, Boris Bikbov 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: (No Response) ******** 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: Partly Reviewer #2: Partly ****** 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: No Reviewer #2: No ****** 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 authors have revised the document, but there remains inherent inconsistencies with the data. Authors have 230 patients who did not have baseline within 3 months and were excluded. Did these patients have baseline creatinine in last 12 months? For other patients, baseline creatinine within a year was considered and there is no clear explanation offered by the authors. The manuscript still has conflicting use of mortality and survival Eg: page 14 The study is retrospective observational study and consent was taken at the time of hospitalization. The conclusion states that this is prospective study There are too many unnecessary tables. On page 14, please ensure confidence interval is correctly reported. Kaplan Meier curve has time on x-axis, which does not make sense and should have days. Even with days, Kaplan Meier curve is inappropriate for short duration of follow-up of 28 days and does not add any information on long–term outcome Reviewer #2: Dear authors, The manuscript makes a different contribution to the understanding and management of patients with AKI-Covid. I highlight the data on the mortality score for AKI-Covid. However, the manuscript needs adjustments: Abstract -Use the KDIGO standardized nomenclature for renal replacement therapy-RRT (throughout the text) instead of KRT. -Conclusions: add data on mechanical ventilation and LRA. Introduction -Subsidize with more references. Sugestions: https://pubmed.ncbi.nlm.nih.gov/32416769 https://pubmed.ncbi.nlm.nih.gov/34033655 Methods - I would like to see the ethics committee protocol number. Results -Format the tables. They are presented in frame format. -I suggest unifying the results of tables 3 and 4; 5 and 6. -Present the score data only with figure 4. Leave table 7 in the supplementary material. - Figure 1 is incomplete. Please enter the subdivisions of patients who were elected in the study. Discussion -Increase the number of references. -Better discuss the findings For example: The Body Mass Index was high and although without statistical relevance in your study, it has been observed that overweight and obesity are risk factors for covid-19. Att, Reviewer ****** 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: Yes:** CASSIANE DEZOTI DA FONSECA [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.0257619.r003
Revision 2
1 Aug 2021 Author Response Authors response to the reviewers We appreciate the excellent work of the reviewers, without a doubt their comments and opinions have been of great value to us, they add greater quality to the manuscript. We humbly hope that our responses will satisfy your requests. Reviewer #1: The authors have revised the document, but there remains inherent inconsistencies with the data. Authors have 230 patients who did not have baseline within 3 months and were excluded. Did these patients have baseline creatinine in last 12 months? For other patients, baseline creatinine within a year was considered and there is no clear explanation offered by the authors. R= These 230 patients who were excluded was because lack of data prior to hospitalization, or who for some reason were not taken in hospitalization. We add in figure 1, point 5, the phrase lack of data. The manuscript still has conflicting use of mortality and survival Eg: page 14 R=We changed the word mortality to survival in page 14. Survival was used when we reported overall survival, the 28-day survival comparing CA-AKI, HA-AKI, and mechanical ventilation (Fig 2), and the 28-day survival between AKI stages and mechanical ventilation (S2 Fig). Mortality was used when we reported the percentage of death among those with different types of AKI (Fig 3), and in the multivariable analysis of variables associated with death (Table 3). The study is retrospective observational study and consent was taken at the time of hospitalization. The conclusion states that this is prospective study. R=The data were recruited prospectively, from the hospitalization of the patients at the time of admission, informed consent was obtained for the storage of information. In the abstract and methods section, we change the word retrospective to prospective. There are too many unnecessary tables. On page 14, please ensure confidence interval is correctly reported. R= Done. We check the confidence intervals, and they are correct. Kaplan Meier curve has time on x-axis, which does not make sense and should have days. Even with days, Kaplan Meier curve is inappropriate for short duration of follow-up of 28 days and does not add any information on long–term outcome. R= The Kaplan-Meier procedure is a method of estimating time-to-event models in the presence of censored cases. The Kaplan-Meier model is based on estimating conditional probabilities at each time point when an event occurs and taking the product limit of those probabilities to estimate the survival rate at each point in time. We understand that the follow-up time is not very long compare to other long-term diseases but due to the severity of the disease that is being analyzed here, the use of a kaplan-meier analysis with a 28-day follow-up is adequate, not to mention that it also offers visual support for greater understanding of the reader. We also add a new supplemental material file with the figures change in DAYS instead of TIME. Reviewer #2: Dear authors, The manuscript makes a different contribution to the understanding and management of patients with AKI-Covid. I highlight the data on the mortality score for AKI-Covid. However, the manuscript needs adjustments: Abstract Use the KDIGO standardized nomenclature for renal replacement therapy-RRT (throughout the text) instead of KRT. R= In the last KDIGO conference report 2020 it was attended to use “kidney” instead of “renal” or “nephro-“. They suggested to use “Kidney replacement therapy” and to avoid “Renal replacement therapy”. Kidney International (2020) 97, 1117–1129; https://doi.org/10.1016/ j.kint.2020.02.010 Conclusions: add data on mechanical ventilation and AKI. Introduction R= We add 6 more references about the strong association between mechanical ventilation and AKI, you can find them in page 20 Subsidize with more references. Sugestions: https://pubmed.ncbi.nlm.nih.gov/32416769 https://pubmed.ncbi.nlm.nih.gov/34033655 R= We appreciate the suggestions of these 2 references, we include interesting information about them in the Discussion, in addition, we add 2 additional ones. You can find them with the number in pages 18, 19 and 20 Methods I would like to see the ethics committee protocol number. R= we add the committee protocol number in methods page 5. The Institutional Review Board of both hospitals (Hospital Civil de Guadalajara HCG/CEI-0473/20 and Centro Medico Nacional 20 de Noviembre 09-240.2020) Results Format the tables. They are presented in frame format. R= done, tables are presented in frame format. I suggest unifying the results of tables 3 and 4; 5 and 6. R= Done. Thanks for the suggestion, tables 3 and 4 ; 5 and 6 were unifying, in there would be only table 3 and 4. You can find them in pages 15, 16 and 17. Present the score data only with figure 4. Leave table 7 in the supplementary material. R= Done. Figure 1 is incomplete. Please enter the subdivisions of patients who were elected in the study. R= done, we included elected patients (in the first square) Discussion Increase the number of references. R= We appreciate the suggestions. We found articles that we consider interesting to include in our manuscript, they were essentially added to the Discussion. You can find in page 17-21. Better discuss the findings For example: The Body Mass Index was high and although without statistical relevance in your study, it has been observed that overweight and obesity are risk factors for covid-19. R=We understand the point of discussing the BMI as an interesting point, we appreciate that you have pointed it out. We add reference 25 (a meta-analysis on the relationship between obesity and COVID) and contrast our findings with this variable in the discussion, we believe that it certainly adds value to our manuscript. Attachments Attachment Submitted filename: response to Reviewer 30_7_21.docx https://doi.org/10.1371/journal.pone.0257619.r004
16 Aug 2021 Decision Letter - Boris Bikbov, Editor PONE-D-21-11844R2 Mortality and evolution between Community and Hospital-acquired COVID-AKI PLOS ONE Dear Dr. Chávez-Iñiguez, 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. There are a few items to correct, mainly considering the terminology. Particularly, this concerns the following: - Please correct the titles of the tables "Univariable-Multivariable logistic regression..." to better readers' perception, and use the coherent terminology in the title and the column names (Univariate/Multivariate); - Please exclude subtitles "-Mortality of CA-AKI vs HA-AKI: ", etc from the "Discussion", changing them with a short introductory phrase. Please submit your revised manuscript by Sep 30 2021 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. 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, Boris Bikbov 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. [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 #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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: Dear authors, The manuscript is much better presented. My suggestions were successfully carried out. I consider the article suitable for publication. ****** 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 #2: Yes:** cassiane dezoti da fonseca [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.0257619.r005
Revision 3
17 Aug 2021 Author Response Response to reviewers We deeply appreciate the comments of the reviewers and are pleased that their requests have been successfully fulfilled. We have made the 2 changes suggested by the editorial committee. - Please correct the titles of the tables "Univariable-Multivariable logistic regression..." to better readers' perception, and use the coherent terminology in the title and the column names (Univariate/Multivariate) R= Done, titles of Table 2 and 3 of the words "Univariable-Multivariable" by "Univariate / Multivariate" -Please exclude subtitles "-Mortality of CA-AKI vs HA-AKI: ", etc from the "Discussion", changing them with a short introductory phrase. R= Done, we exclude subtitles "-Mortality of CA-AKI vs HA-AKI:", "Risk factors for CA-AKI", "KRT between CA-AKI vs HA-AKI" and "Predictive score of death in patients with COVID-AKI" from the "Discussion". We believe that only by deleting those subtitles and leaving the first sentence of each paragraph as it is in the manuscript, the content is perfectly understood, without adding anything else. Attachments Attachment Submitted filename: Response to Reviewers 16_8_21.docx https://doi.org/10.1371/journal.pone.0257619.r006
20 Aug 2021 Decision Letter - Boris Bikbov, Editor PONE-D-21-11844R3 Mortality and evolution between Community and Hospital-acquired COVID-AKI PLOS ONE Dear Dr. Chávez-Iñiguez, 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. Thanks for correcting the minor items mentioned before. The changes you introduced are fine, but since after the acceptance there will be no additional editing, please perform further minor corrections to the tables' title to make it not only technically correct but also more easier to percept by readers who are primary clinicians. For example, the "Table 3. Univariable/Multivariable logistic regression model to determine the variables associated with mortality at 28-days follow up and Kidney replacement therapy in hospitalized COVID patients." could be changed to "Table 3. Factors associated with mortality at 28-days of follow up and the requirement of kidney replacement therapy in hospitalized COVID patients, in the univariable and multivariable logistic regression model." This is just an example, you could change the titles in your own way, but I hope this example demonstrates the idea. Please also change the terminology used in the table ("Grade COVID" -> "COVID severity", "Mechanical ventilator" -> "Need in mechanical lung ventilation") and also in the manuscript text ("ventilator" -> "ventilation", etc). You have prepared a nice manuscript with valuable results, there is only a need to polish a little bit the terminology. Please submit your revised manuscript by Oct 04 2021 11:59PM. 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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. 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, Boris Bikbov 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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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.0257619.r007
Revision 4
24 Aug 2021 Author Response Response to reviewers We deeply appreciate the comments of the reviewers and are pleased that their requests have been successfully fulfilled. We have welcomed comments from the Academic Editor Boris Bikbov about minor edits to the tables and text, which we have corrected according to their instructions. Now the manuscript is easier to read. "Table 3. Univariable/Multivariable logistic regression model to determine the variables associated with mortality at 28-days follow up and Kidney replacement therapy in hospitalized COVID patients." could be changed to "Table 3. Factors associated with mortality at 28-days of follow up and the requirement of kidney replacement therapy in hospitalized COVID patients, in the univariable and multivariable logistic regression model." This is just an example, you could change the titles in your own way, but I hope this example demonstrates the idea. R=Done, The changes have been made in table 3 and 4 with the editor's suggestions, now it is as follows: Table 3. Factors associated with mortality at 28-days of follow up and the requirement of kidney replacement therapy in hospitalized COVID patients, in the univariable and multivariable logistic regression model. (page 16) Table 4. Factors associated with CA-AKI and HA-AKI in hospitalized COVID patients, in the univariable and multivariable logistic regression model. (page 17) Please also change the terminology used in the table ("Grade COVID" -> "COVID severity", "Mechanical ventilator" -> "Need in mechanical lung ventilation") and also in the manuscript text ("ventilator" -> "ventilation", etc). R= Done, we have made the changes suggested by the Editor in tables and the manuscript, of the terms: grade COVID, mechanical ventilator; by the terms: COVID severity, Need in mechanical lung ventilation. We really hope that this changes satisfy to the Academic Editor. Attachments Attachment Submitted filename: Response to Reviewers 21_8_21.docx https://doi.org/10.1371/journal.pone.0257619.r008
6 Sep 2021 Decision Letter - Boris Bikbov, Editor Mortality and evolution between Community and Hospital-acquired COVID-AKI PONE-D-21-11844R4 Dear Dr. Chávez-Iñiguez, 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, Boris Bikbov Academic Editor PLOS ONE Additional Editor Comments (optional): ACADEMIC EDITOR: Please note there are some terminology and formatting incongruences in the tables. For example, the tables' title indicates "... in the univariable and multivariable logistic regression model" that is fine. However, the authors have left the column names as "Univariate (95% CI)" and "Multivariate (95% CI)" - that is not correct and should be "Univariable analysis, OR (95% CI)". In another table the authors compared 2 groups and named the column with p-value as "P value (CA-AKI vs. HA-AKI)", with excessive detail "(CA-AKI vs. HA-AKI)" because that are the groups' names. The journal office will include the requested edits as part of the final requirements the authors must complete before editorial acceptance. Please correct these formatting incongruencies before the manuscript can be editorially accepted. Reviewers' comments: https://doi.org/10.1371/journal.pone.0257619.r009
Formally Accepted
26 Oct 2021 Acceptance Letter - Boris Bikbov, Editor PONE-D-21-11844R4 Mortality and evolution between Community and Hospital-acquired COVID-AKI Dear Dr. Chávez-Iñiguez: 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. Boris Bikbov Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0257619.r010

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