Systemic immune-inflammatory indicators and bone mineral density in chronic kidney disease patients: A cross-sectional research from NHANES 2011 to 2018

Yuying Jiang; Xiaorong Bao

doi:10.1371/journal.pone.0302073

Peer Review History

Original SubmissionJanuary 29, 2024
6 Mar 2024 Decision Letter - Ewa Tomaszewska, Editor PONE-D-24-02266Systemic Immune-inflammatory Indicators and Bone Mineral Density in Chronic Kidney Disease Patients: A Cross-sectional Research from NHANES 2011 to 2018PLOS ONE Dear Dr. Bao, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Apr 20 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 upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: I reviewed the article sent to me for review - "Systemic markers of immune inflammation and bone mineral density in patients with chronic kidney disease: a cross-sectional study from NHANES 2011–2018" The presented research work may not be groundbreaking in its assumptions, as it has been known for years that CKD and high levels of inflammatory parameters reduce bone mineral density, but the work meets the publication requirements. I believe that the work is valuable due to the research and breadth of the group analyzed. Reviewer #2: 1. eGFR needs superscripts for the 2's of the unit species. 2. line 58-59 '[value -0.008; 95% confidence interval (CI) -0.014, -0.002]' Please change to [β=-0.008; 95% confidence value -0.008; 95% confidence interval (CI) -0.014, -0.002]'. 3. From table 1 kind of it can be seen that there are very few participants with BMI<18, I suggest that the authors can combine them in the group with BMI<25 only, in addition, the square meters in the units of BMI need to be superscripted. 4. on what basis did the authors choose these covariates? 5. the authors excluded non-compliant participants from the initial group of about 20,000 participants and ended up with about 2,000 participants left to be included in the analysis. does this exclusion result in a selective bias in the sample? 6. It is recommended that the authors add a discussion of SII-related studies to the discussion: I suggest citing the following literature: 1. doi: 10.3389/fimmu.2022.925690 2. doi: 10.1016/j.numecd.2023.04.015 ****** 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. 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Revision 1
19 Mar 2024 Author Response Dear Editor and Reviewers, We appreciate the opportunity to allow us to revise our manuscript and thanks for the reviewers’ constructive comments and suggestions. We would like to submit our revised manuscript, entitled ‘Systemic Immune-inflammatory Indicators and Bone Mineral Density in Chronic Kidney Disease Patients: A Cross-sectional Research from NHANES 2011 to 2018’ for consideration for publication. In the revised manuscript, we have carefully addressed all comments and questions raised by reviewers point-by-point. We greatly appreciate your time and efforts to improve our manuscript for publication. Reply to Reviewers Reviewer #1: 1． I reviewed the article sent to me for review - "Systemic markers of immune inflammation and bone mineral density in patients with chronic kidney disease: a cross-sectional study from NHANES 2011–2018" The presented research work may not be groundbreaking in its assumptions, as it has been known for years that CKD and high levels of inflammatory parameters reduce bone mineral density, but the work meets the publication requirements. I believe that the work is valuable due to the research and breadth of the group analyzed. Reply: We sincerely appreciate your acknowledgment of the importance of our study and the paper. We selected SII, a novel parameter combining platelets, neutrophils, and lymphocytes, to quantitatively explore the clinical significance of the inflammatory response in the development of complications in CKD patients and to increase the confidence of the results by expanding the sample size, even though it is already widely known that the combined systemic inflammatory response in CKD patients reduces BMD. We will also investigate the precise mechanisms linking the two in more detail in later research to provide ground-breaking outcomes. Once again, thank you for your confirmation. Please don't hesitate to contact us if you have any further queries or require any clarification. Reviewer #2: Concerns: 1． eGFR needs superscripts for the 2's of the unit species. Reply: We appreciate your insightful feedback, and we have updated the entire text to include all non-standard units of measurement. Going forward, we'll make sure to focus more on the pertinent aspects of our research. 2． line 58-59 '[value -0.008; 95% confidence interval (CI) -0.014, -0.002]' Please change to [β=-0.008; 95% confidence value -0.008; 95% confidence interval (CI) -0.014, -0.002]'. Reply: Thank you very much for your valuable comments, we have revised this part according to the review comments. 3． From Table 1 kind of it can be seen that there are very few participants with BMI<18, I suggest that the authors combine them in the group with BMI<25 only, in addition, the square meters in the units of BMI need to be superscripted. Reply: We appreciate your insightful feedback. We have superscripted the square meter needs in terms of BMI and merged participants with a BMI <18 kg/m2 in the BMI <25kg/m2 category. In our next job, we'll also take extra care with these aspects. . 4． On what basis did the authors choose these covariates? Reply: Thank you very much for pointing out this deficiency. During the inclusion of covariates, we considered three aspects that affect the duration of CKD, the body's inflammatory response, and changes in bone mineral density, so we reviewed the relevant literature and referred to our own experience in clinical practice to determine the covariates to be included in the study. We included gender, age, and race as demographic data because this affects the general condition of the patients. Urine albumin, urine creatinine, urine creatinine/albumin ratio, blood urea nitrogen, blood creatinine, blood uric acid, and GFR are often used to assess disease progression in patients with CKD. The presence of hypertension, diabetes mellitus, and obesity, on the other hand, have been shown to influence further deterioration of renal function. Blood alkaline phosphatase, blood calcium, blood triglycerides, blood phosphorus, and vitamin D are closely related to bone metabolism. Taking all these considerations into account, we finally included these covariates. 5． the authors excluded non-compliant participants from the initial group of about 20,000 participants and ended up with about 2,000 participants left to be included in the analysis. does this exclusion result in a selective bias in the sample? Reply: We much appreciate your candid counsel. We did take into consideration the possibility that, had missing data and patients not diagnosed with CKD been removed from the study because non-randomization was used, there would have been differences between the study population and the target population represented, which would have diminished the validity of the study's conclusions. We increased the sample size by including 8 years of data, spanning from 2011 to 2018, to reduce this mistake. The website also suggests combining multiple years of data to increase the sample size and thereby reduce error, given the history of the NHANES database with the oversampling of certain subgroups and the limited analytical utility of a 2-year sample to provide estimates for subgroups with lower percentages of population distribution. To minimize mistakes, we took this action and included in the study all eligible patients. To lessen confounding in the study and lower the error in the conclusions, we also performed stratified analyses and built multivariate analytic models. We do think about utilizing more public datasets or conducting follow-up research using actual studies to better establish the study's legitimacy. Once again, I appreciate your thoughtful suggestions. 6． It is recommended that the authors add a discussion of SII-related studies to the discussion. I suggest citing the following literature: doi: 10.3389/fimmu.2022.925690\\ doi: 10.1016/j.numecd.2023.04.015 Reply: We appreciate you pointing us in the direction of the well-researched literature, which goes into additional detail about the clinical importance of SII in various contexts. Based on your suggestion and after carefully reviewing the research, we have updated the discussion section to provide a fresh analysis of the significance of SII in the diagnosis and prognosis of other diseases. The citations for the sources you suggested are found in lines 342–359. Furthermore, it has been demonstrated that SII is related to abdominal aortic atherosclerosis, a typical consequence of advanced CKD, which offers suggestions for further research. Once again, I appreciate your advice and manuscript recommendation. Line 342–357, fourth paragraph of the Discussion section: According to a 2014 study by Hu [15] et al., SII is a thorough and unique inflammatory biomarker. Prior research has routinely employed SII as a predictor of the development of kidney transplant rejection as well as the incidence of acute or chronic renal injury [34–38]. Numerous studies connected to SII have been conducted in recent years, and they have thoroughly examined its clinical importance. Lai et al. [34] in a cohort study showed that elevated levels of SII before CAG were an important and independent risk factor for postoperative AKI, and Halpern et al. [40] in a single-center cohort study showed that elevated levels of SII were independently associated with increased survival only in post-transplant patients. For instance, Xie et al. [39] in 2022 found that elevated levels of SII were associated with hepatic steatosis but not with hepatic fibrosis. A cohort study was conducted by Halpern et al. in one center. Regarding prognosis, prospective cohort research by Shi [31] et al. showed that in CKD patients with ACS, higher SII was linked to poor cardiovascular outcomes. In a similar vein, Xie et al. [41] discovered a favorable correlation between SII and abdominal aortic calcification, a frequent CKD consequence. In a cohort investigation of critically ill AKI patients, Lan et al. [42] discovered a J-shaped relationship between SII and all-cause death in these patients. All of these suggestions are insightful and help us polish our manuscript considerably. We made every effort to make the manuscript better. The paper's structure and content won't be impacted by these modifications. We sincerely thank the editors and reviewers for their hard work, and we hope that the corrections will be accepted. Kindly do not hesitate to get in touch with us if you have any more inquiries or suggestions. I express my gratitude once more for your insightful remarks and recommendations. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0302073.r002
27 Mar 2024 Decision Letter - Ewa Tomaszewska, Editor Systemic Immune-inflammatory Indicators and Bone Mineral Density in Chronic Kidney Disease Patients: A Cross-sectional Research from NHANES 2011 to 2018 PONE-D-24-02266R1 Dear Dr. Xiaorong Bao, 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, Ewa Tomaszewska, DVM 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 #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: The authors completed a good scientific research. I have no further comments. Thank you so much for your efforts. ****** 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: No ******** https://doi.org/10.1371/journal.pone.0302073.r003
Formally Accepted
3 Apr 2024 Acceptance Letter - Ewa Tomaszewska, Editor PONE-D-24-02266R1 PLOS ONE Dear Dr. Bao, 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 Professor Ewa Tomaszewska Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0302073.r004

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