Association between systemic immune-inflammation index and chronic kidney disease: A population-based study

Lin Li; Kunfei Chen; Chengping Wen; Xiaoqin Ma; Lin Huang

doi:10.1371/journal.pone.0292646

Peer Review History

Original SubmissionApril 27, 2023
28 Jun 2023 Decision Letter - Innocent Ijezie Chukwuonye, Editor PONE-D-23-11993Association between systemic immune-inflammation index and chronic kidney disease: a population-based studyPLOS ONE Dear Dr. Ma, 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 some additional corrections that I observed should be made to this manuscript in addition to those observed by the reviewers, and these are reflected in the manuscript attached. Please submit your revised manuscript by Aug 12 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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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. Thank you for stating the following financial disclosure: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” At this time, please address the following queries: a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b) State what role the funders took in the study. 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Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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: The authors carried out cross-sectional study and conducted multivariate logistic regression and smoothing curves and threshold effect analyses to explore the association between SII and CKD in the adult US population. Concerns with the study design and statistical analysis are as follows: 1.Please analysis the association between CKD stage and SII if GFR data were available 2.The authors found a Inflection point in linear regression models（SI=2100). But a linear trend was found in table 3. Please provide concrete value of each quartile in Table 3 Reviewer #2: This is a novel work, written in a simple style to aid understanding. A few critical points to note: 1. Are the excluded participants systemically different form those included in the study? especially as regards age and gender distribution. This may impact on the CKD classification. 2. The definition of CKD usually requires at least 2 eGFR or uACR values obtained at least 3 months apart. It appears this study had single values for both eGFR and uACR which may affect the classification of CKD. Some of the individuals may have an AKI, thereby causing an overestimation of CKD. AKI, on its own, is an inflammatory condition which may affect SII values. This may invalidate our findings. 3. It appear the 2009 CKD-EPI equation (with race factor) was used for this analysis. This has been shown to inaccurately estimate eGFR. The more recent (and accurate) revision of the equation (DOI: 10.1056/NEJMoa2102953), should be used. The number of participants with CKD will change when the new equation is applied. This is the most important limitation of this study and should be addressed. 4. Is there a statistical trend for SII across the 5 stages of CKD? It would be good to investigate for this. ****** 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. Attachments Attachment Submitted filename: Manuscript(2).docx https://doi.org/10.1371/journal.pone.0292646.r001
Revision 1
22 Sep 2023 Author Response Dear Editor and Reviewers, We appreciate the opportunity to allow us to revise our manuscript and thanks for reviewers’ constructive comments and suggestions. Firstly, We are very sorry for the delay in revising the draft due to sudden personal problems. Once again, we would like to express my sincere apologies. We would like to submit our revised manuscript, entitled ‘Association between systemic immune-inflammation index and chronic kidney disease: a population-based study’ 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: The authors carried out cross-sectional study and conducted multivariate logistic regression and smoothing curves and threshold effect analyses to explore the association between SII and CKD in the adult US population. Concerns with the study design and statistical analysis are as follows: 1.Please analysis the association between CKD stage and SII if GFR data were available Reply: Thank you very much for your valuable comments. We re-completed a statistical analysis of the relationship between CKD stage and SII based on GFR data. The new results can be seen in Supplementary Tables 1&2. 2.The authors found a Inflection point in linear regression models（SII=2100). But a linear trend was found in table. Reply: Thank you for your helpful question, which is well worth investigating. As you proposed, although our curve fitting presents atypical U-shaped or inverted U-shaped associations, inflection points are found in the threshold analysis (p for log-likelihood ratio=0.004). When SII < 2100 (1000 cells/µl), SII was positively correlated with CKD,and SII was an independent risk element for CKD. And when SII > 2100 (1000 cells/µl), there was no statistically significant association between SII and CKD.Therefore, according to this inflection point, it can be suggested that when we further explore the relationship between SII and CKD, it is more appropriate when SII < 2000(1000 cells/µl). The added description is shown in red in the paper. 3. Please provide concrete value of each quartile in Table 3. Reply: Thank you very much for your professional guidance, which is of great help to our article. We have added specific values for each quartile based on your suggestion in Table 3. (See red in Table 3 for details) Reviewer #2: This is a novel work, written in a simple style to aid understanding. A few critical points to note: 1.Are the excluded participants systemically different form those included in the study? especially as regards age and gender distribution. This may impact on the CKD classification. Reply: Thank you very much for your valuable comments. First, excluded participants included: 1. Missing SII data (14444) 2. Missing CKD data (6028) 3. Age below 20 (19180). Since only adult participants were studied, in the age distribution, subjects younger than 20 years of age were present only in the excluded population. In addition to that, we have made a baseline table of excluded participants（See table below）based on demographic variables such as age/gender/race, showing that the mean age of excluded participants is 13.3 ± 13.4, which is different from that of included adult participants(49.77 ± 18.04) due to the excessive number of excluded participants under the age of 20 (n=19180). Age and gender remained independent risk factors for CKD (P < 0.001). In addition, among excluded participants, CKD patients were mostly white, female，which is consistent with included participants. Due to the low mean age of the excluded participants, the results were mostly those who were Less than high school, never married, more poor, BMI < 25, no abdominal obesity, no smoke, no drink, no hypertension and diabetes. Therefore, in order to achieve objective results without affecting the diagnosis and staging of CKD, participants younger than 20 years of age should be excluded due to their greater impact on the results. Weighted characteristics of the excluded participation categorized by CKD status.(See the document for the table: Response letter.docx) Overall No CKD CKD p-Value N=39652 N= 34339(86.6%) N=5313(13.4%) Age (Mean ±SD, years) 13.3 ± 13.4 15.65 ± 11.71 17.01 ± 16.24 <0.0001 Gender (%) <0.0001 Male 50.8 53.3 38.01 Female 49.2 46.7 61.99 Race (%) 0.0132 Mexican American 16.5 16.82 16.03 Non-Hispanic White 38.5 34.12 34.21 Non-Hispanic Black 20.7 22.6 23.47 Other Hispanic 9.7 10.68 9.04 Other Race 14.5 15.77 17.25 Education (%） <0.0001 Less than high school 80.6 81.67 85.72 High school 8.4 8.16 5.9 More than high school 11 10.17 8.38 Marital status (%) <0.0001 Never married 55.1 59.9 51.4 Maried/Living with Partner 32.9 31.13 28.23 Widowed/Divorced /Separated 12 8.97 20.38 Poverty ratio (%) 0.0018 0-1.5 44.9 44.16 40.98 1.5-3.5 25.1 24.9 27.42 >3.5 29.9 30.93 31.59 BMI (kg/m², %) <0.0001 ＜25 77.1 72.15 82.2 25-29.9 12.6 15.5 8.94 ≥30 10.3 12.35 8.85 Abdominal obesity (%) 0.1825 No 90.1 88.18 89.02 Yes 9.9 11.82 10.98 Drinking status (%) <0.0001 Never 22 21.76 20.23 Former 10.5 9.32 18.6 Mild 27 26.17 34.07 Moderate 15.3 16.05 9.04 Heavy 25.2 26.7 18.06 Smoking status (%) <0.0001 Never 62.6 65.57 53.53 Former 17.2 16.58 24.13 Now 20.2 17.85 22.34 Hypertension (%) <0.0001 No 92.6 94.31 89.17 Yes 7.4 5.69 10.83 Diabetes (%) <0.0001 No 98.5 98.49 96.16 Yes 1.5 1.51 3.84 SII (Mean±SD,1,000cells/µl) 437.8 ± 300.6 461.99 ± 296.11 455.29 ± 293.16 0.2894 2.The definition of CKD usually requires at least 2 eGFR or uACR values obtained at least 3 months apart. It appears this study had single values for both eGFR and uACR which may affect the classification of CKD. Some of the individuals may have an AKI, thereby causing an overestimation of CKD. AKI, on its own, is an inflammatory condition which may affect SII values. This may invalidate our findings. Reply: Thank you for your professional advice, which has been of great help to the improvement of our article. As you pointed out, for the diagnosis of CKD, it is usually more accurate to have at least 2 eGFR or uACR values at least 3 months apart, but we are sorry that the NHANES database is a cross-sectional study with only one test value, which is also a limitation of many cohorts or databases. In addition, AKI is not yet clear in this database, so we have added it to the limitations in the discussion section.(See red in discussion for details) 3.It appear the 2009 CKD-EPI equation (with race factor) was used for this analysis. This has been shown to inaccurately estimate eGFR. The more recent (and accurate) revision of the equation (DOI: 10.1056/NEJMoa2102953), should be used. The number of participants with CKD will change when the new equation is applied. This is the most important limitation of this study and should be addressed. Reply: Thank you very much for your valuable comments. Due to the incomplete follow-up data of the 2019-2022 NHANES database, this study only included the data of 2003-2018, and used the earlier version (2009) for formula selection. Based on your valuable comments, we have carefully studied and compared the new formula of 2021 with the formula of 2009, and found that the accuracy of the formula of 2021 is slightly lower than that of 2009 CKD-EPI creatinine formula【1-2】, so we hope to continue to use the formula of 2009. 【1】Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021;385(19):1737-1749. doi:10.1056/NEJMoa2102953 (IF: 158.5, Q1) 【2】Hsu CY, Yang W, Parikh RV, et al. Race, Genetic Ancestry, and Estimating Kidney Function in CKD. N Engl J Med. 2021;385(19):1750-1760. doi:10.1056/NEJMoa2103753 (IF: 158.5, Q1) 4. Is there a statistical trend for SII across the 5 stages of CKD? It would be good to investigate for this. Reply: Thank you very much for your valuable comments. We re-completed a statistical analysis of the relationship between CKD stage（G1,G2,G3a,G3b,G4,G5） and SII. The new results can be seen in supplementary Tables 1&2 and in the sentences marked in red in the results section of the revised manuscript. Finally We marked the changes in red in the revised paper. We have also added references, adding Supplementary Figures 1 and 2. We have changed the manuscript according to the request using PLOS ONE' s style and added the Funding section. These comments are all valuable and enable us to greatly improve the quality of our manuscript. We tried our best to improve the manuscript. These changes will not influence the content and framework of the paper. We appreciate for Editors/Reviewers’ warm work earnestly and hope that the corrections will meet with approval. Please do not hesitate to contact us with any further questions or recommendations. Once again, thank you very much for your comments and suggestions. Attachments Attachment Submitted filename: Response letter.docx https://doi.org/10.1371/journal.pone.0292646.r002
26 Sep 2023 Decision Letter - Innocent Ijezie Chukwuonye, Editor Association between systemic immune-inflammation index and chronic kidney disease: a population-based study PONE-D-23-11993R1 Dear Lin Huang 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, Innocent Ijezie Chukwuonye, MBBS, FMCP (Internal Medicine) Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0292646.r003
Formally Accepted
3 Oct 2023 Acceptance Letter - Innocent Ijezie Chukwuonye, Editor PONE-D-23-11993R1 Association between systemic immune-inflammation index and chronic kidney disease: a population-based study Dear Dr. Ma: 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. Innocent Ijezie Chukwuonye Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0292646.r004

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