The impact of serum potassium ion variability on 28-day mortality in ICU patients

YuChou Zhang; ShengDe Liang; HanChun Wen

doi:10.1371/journal.pone.0310046

Peer Review History

Original SubmissionMay 25, 2024
2 Jul 2024 Decision Letter - Tatsuo Shimosawa, Editor PONE-D-24-19608The Impact of Serum Potassium Ion Variability on 28-Day Mortality in ICU PatientsPLOS ONE Dear Dr. Zhang, 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. Two experts raised several concerns to be clarified. Please submit your revised manuscript by Aug 16 2024 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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Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: 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 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: Authors have investigated the correlation between variability of serum K and mortality and have found that the higher variability was associated with higher morality. I found the results very interesting and novel, which merits publication. However, some comments needs to be answered before acceptance. 1) Since it is well known that mortality is associated with extreme values of sK, in order to exclude the effect of severe hypo- of heperkalemia in terms of mortality, I would recommend to check the correlation between CV and moratality only in those without experiencing extreme values (for example, sK<3, >6) in addition to whole analysis. This analysis should serve as a sensitivity analysis. 2) Significant change in sK can occur especially in those with hemodialysis or CRRT. I would recommend to add renal replacement therapy (yes or no) as a variable in the analysis. 3) Also, sK change can be exaggerated in those with lreduced kidney function. It looks like "renal insufficiency" is rare in the study population, how you define "renal insufficiency"? I would like to see the effect of degree of eGFR to the CV of sK and also to the mortality. Reviewer #2: In patients requiring ICU management, the best relationship between death and K value is around 4.0, as previously reported. The paper also attempts to prove that a lower coefficient of variation of K is associated with an increased risk of 28-day mortality, which is an interesting point of view. However, in order to prove this, the following issues need to be resolved. Major comment ①Overall, the correlation between K values and mortality has been reported in large clinical studies. The total number of patients is 237, which is too small to statistically correlate. It is necessary to increase the number of patients to examine the correlation. ➁The period of observation is slightly different and more detailed data is needed to correlate the one-week variation in CV of K-values with the risk of death during 28 days. (If possible, K values and CV values should also be listed for up to 28 days.) ③The K-adjustment method for dialysis patients is different from that for other patients, so separate analyses are recommended. Minor comment ①In Table 2 Covariates, P value is described from Male to PH, but OR (95%) is described. Confirmation is needed. ➁It is necessary to list the mean K values before admission to ICU and at 28 days. ③The report concludes that there is a significant difference by sex (male), but it is necessary to explain the reason for this in the discussion. ****** 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? 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Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0310046.r001
Revision 1
1 Aug 2024 Author Response We thank the reviewers for their valuable comments, which certainly help us to improve the quality of our manuscript. All comments are addressed on a point-by-point basis below, where letters C & R denote Comment and Response, respectively. Reviewer#1: C:1)Since it is well known that the portality is associated with extreme values of sK,in order to exclude the effect of evere hypo-ofhepercalemia and termsofortality, I would recommend checking the correlation between CV and moratality only in those without experiencing extreme values(for example,sK<3,>6)inaddition to wholel analysis.This analysis should serve as a sensitivy analysis. R:1)Thank you for your feedback, I agree with your point of view. Therefore, I established three statistical models. Patients with K>6, K<3, K>6, and K<3 were excluded and reanalyzed. Table 2 in Appendix 6 shows that all three statistical models are significant. C:2)Significant change in sK can occur especially in those with hemodialysis or CRRT. I would recommend to add renal replacement therapy (yes or no) as a variable in the analysis. R:2)Thank you for your suggestion. I agree with your viewpoint. We added the variable of hemodialysis to the statistical model and found P<0.01 (model 4 in Appendix 6). Moreover, after excluding patients undergoing hemodialysis and reanalyzing, it was found to still be significant (Table 4 in Appendix 6). C:3)Also, sK change can be exaggerated in those with lreduced kidney function. It looks like "renal insufficiency" is rare in the study population, how you define "renal insufficiency"? I would like to see the effect of degree of eGFR to the CV of sK and also to the mortality. R:3)Thank you for your valuable feedback. We have made improvements based on your feedback. ICD-10-diagnoses were determined by physicians depending on the guidelines valid at the time. ICD-10-GM derived covariates are as followed: Renal Insufficiency N18.001-N18.004. eGFR was calculated based on age, gender, and creatinine levels. After incorporating the covariate eGFR into the statistical model, it showed significant differences (P=0.03) (Model 5). In addition, Appendix 5 shows a significant difference in eGFR between the death group and the inventory group. Reviewer#2 C:1）Overall, the correlation between K values and mortality has been reported in large clinical studies.The total number of patients is 237, which is too small to statistically correlate. It is necessary to increase the number of patients to examine the correlation. R:1）Thank you for your suggestion. We agree with your opinion, so we have increased the sample size and reanalyzed the article. C:2）The period of observation is slightly different and more detailed data is needed to correlate the one-week variation in CV of K-values with the risk of death during 28 days. (If possible, K values and CV values should also be listed for up to 28 days.) R:2）Thank you for your suggestion. We agree with your viewpoint. We increased the observation period of K to 28 days, and then collected relevant data and reanalyzed it. C:3）The K-adjustment method for dialysis patients is different from that for other patients, so separate analyses are recommended. R:3）We agree with your viewpoint. Therefore, we excluded patients who had undergone blood purification from the statistical model and conducted reanalysis, and the results still showed significance (Table 4 in Appendix 6) C:4）In Table 2 Covariates, P value is described from Male to PH, but OR (95%) is described. Confirmation is needed. R:4）Thank you for your feedback. Table 2 describes OR (95% CI). C:5）It is necessary to list the mean K values before admission to ICU and at 28 days. R:5）Thank you for your suggestion. We collected potassium values within 28 days of ICU and reanalyzed them. C:6）The report concludes that there is a significant difference by sex (male), but it is necessary to explain the reason for this in the discussion. R:6）We agree with your opinion and have made revisions in the article. For the significance of men in the statistical model, relevant literature points out that male or female exposure may affect the incidence rate and prognosis of various critical diseases throughout the life cycle. Biological differences, sex hormone and cytokine responses may lead to observed gender differences, but the mechanisms underlying these gender differences cannot currently be explained. Attachments Attachment Submitted filename: Response to Reviewers.pdf https://doi.org/10.1371/journal.pone.0310046.r002
16 Aug 2024 Decision Letter - Tatsuo Shimosawa, Editor The Impact of Serum Potassium Ion Variability on 28-Day Mortality in ICU Patients PONE-D-24-19608R1 Dear Dr. Zhang, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: All comments are fairly well answered and appropriate revisions have been made. I have no further comments. Reviewer #2: (No Response) ****** 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 ******** https://doi.org/10.1371/journal.pone.0310046.r003
Formally Accepted
30 Aug 2024 Acceptance Letter - Tatsuo Shimosawa, Editor PONE-D-24-19608R1 PLOS ONE Dear Dr. Zhang, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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.0310046.r004

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