Serum uric acid level and all-cause and cardiovascular mortality in peritoneal dialysis patients: A systematic review and dose-response meta-analysis of cohort studies

Ting Kang; Youchun Hu; Xuemin Huang; Adwoa N. Amoah; Quanjun Lyu

doi:10.1371/journal.pone.0264340

Peer Review History

Original SubmissionJuly 9, 2021
5 Nov 2021 Decision Letter - Girish Chandra Bhatt, Editor PONE-D-21-22383Serum uric acid level and all-cause and CVD mortality in peritoneal dialysis patients: A systematic review and meta-analysis of cohort studiesPLOS ONE Dear Dr. Lyu, 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. ACADEMIC EDITOR:High heterogeniety is observed in result section for some outcomes, need for some more statistical analysis as given. Some minor language polishing is required in abstract and the main manuscript Please submit your revised manuscript by Dec 20 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. 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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. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Additional Editor Comments: Details of how NOS quality assessment of each study should be provided in the table. Wherever unexplained high heterogeneity is present i.e >50% , the authors should use methods such as Bejout;s curve, influential analysis and leave one out analysis. Visual inspection of the funnel plot for publication bias is used when the number of the studies is more than or equal to 10 for a particular outcome. Moreover, other test such as Egger;s test should be usede and provided as being significant or non -significant. [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: Serum uric acid level and all cause mortality and cardiovascular mortality in peritoneal dialysis patients: A systematic review and meta-analysis of cohort studies. Introduction: The introduction highlights the facts that serum uric acid is a know cause on increased mortality in patients on dialysis. There is conflicting data on the association of uric acid with mortality in patients on PD and the method of estimation of uric acid. The authors may re-frame the sentences to allow easy comprehension and improve clarity. The objective may also be re-framed “to determine the association…..” Methods: The methods mention that studies in all languages were included, but the interpretation of studies in a foreign language has not been described. Were any attempts made to search for unpublished data (conference proceedings etc?). Cochrane library was not included in the literature search. The systematic review /meta-analysis has not been registered in any database. The systematic review has assessed the bias of risk, assessed quality of the data and accounted for publication bias. Results: The results have been discussed well. The Forest plots however are not very clear. The PRISMA reporting guidelines have been followed. Discussion: The fact that most of the studies were from Asian countries limits its generalizability to the global population Conclusions: The conclusions are aligned to the objectives ****** 6. 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Revision 1
9 Dec 2021 Author Response Response to Academic Editor: To explore the source of heterogeneity among studies, subgroup analyses were conducted according to study design (prospective or retrospective cohort study), number of center (multi-center or single center), publication years (2013-2016 or 2017-2020), sample size (< 900 or > 900), follow-up duration (< 30 months or > 30 months), adjustment for gender and adjustment for diabetes status. And we also carefully revised the content and grammar of our article, hoping to improve the article. Response to additional Editor: To question 1: We provided details of NOS quality assessment for each study in the S2 Table. To question 2: Sensitivity analysis, in which 1 study was removed at a time, was performed to evaluate the stability of the results. We added several sensitivity analyses, and the results are shown in S1-S6 Figs. To question 3: It is really true as editor suggested that visual inspection of the funnel plot for publication bias is used when the number of the studies is more than or equal to 10 for a particular outcome. Therefore, we deleted the funnel plots and recorded the P values of egger’s test in the manuscript. Response to Reviewer: To question 1: We re-framed the objective of this study as follows: hence, the objective of this study is to determine the association between SUA and all-cause and CVD mortality with a detailed analysis of eligible literature. To question 2: (1) We have re-written this part according to the Reviewer’s suggestion: all non-English studies were translated by software first, and then the researchers checked whether they could be included. (2) In addition to a comprehensive search, we considered the reference lists of all eligible articles in order to find additional relevant articles. I regret that unpublished data was not considered. (3) We are very sorry that we did not search the Cochrane Library database before. Therefore, we limited the date filter to April 7, 2021, and finally retrieved 27 literatures (See S1 Table for searching strategies). (4) We are very sorry that we did not register for this meta-analysis, but we conducted this systematic review and meta-analysis in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To question 3: We have adjusted the resolution and size of the figures, hoping to meet the requirements of the journal. To question 4: After consideration, we have included a conference abstract by Coelho et al [1] in Portugal, but the pooled results did not change. Nevertheless, almost all the studies included in the meta-analysis were conducted in Asian countries, which greatly limits the applicability of the results to the global population. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0264340.r002
21 Jan 2022 Decision Letter - Masaki Mogi, Editor PONE-D-21-22383R1Serum uric acid level and all-cause and cardiovascular mortality in peritoneal dialysis patients: a systematic review and dose-response meta-analysis of cohort studiesPLOS ONE Dear Dr. Lyu, 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. The manuscript is still necessary to be revised to be improve the paper quality according to the Reviewer's comments. Please submit your revised manuscript by Mar 07 2022 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: https://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, Masaki Mogi 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: All comments have been addressed 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: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The authors have responded to all the queries satisfactorily and made the necessary changes in the revised manuscript Reviewer #2: The authors conducted a very careful systematic review and presented valuable data on association between serum uric acid levels and all-cause mortality or CVD in PD patients. It is very interesting data, and since this study contains enough subjects, subgroup analysis became possible. So, several concerns should be addressed. Major comments #1 It is interesting that there is no significant difference in the subgroup analysis (Table 1 and Table2) when adjusted with gender and diabetes, suggesting there is a difference in the impact of uric acid in these subgroups. Are such analyses possible? Or, authors should discuss on these points and data of subgroup analyses (Table 1, Table2). #2 The patients with hyperuricemia consists of etiologically heterogeneous population. Serum uric acid levels are affected by genetic predisposition for uric acid transporters, and also by environmental factors such as alcohol drinking and obesity/visceral fat accumulation due to overnutrition. The former shows a very high serum uric acid level, and gout and urinary tract stones appear in the foreground, while the latter is prone to atherosclerosis, and may reflect the high CRP that the authors pointed out in Discussion section. Since this study have enough subjects, subgroup analysis is possible, which is very valuable. This time, authors showed the adjusted data by gender and diabetes. Since the authors focused on all-cause mortality and CVD, it may be useful to conduct a subgroup analysis with or without obesity/visceral fat accumulation, and with or without liver dysfunction which reflects NAFLD/NASH. Is it possible that the impact of uric acid will be sharpened by doing so? Minor comments #3 It will become more understandable for readers to show data on the concentration range of the uric acid category in each paper, because the meanings of UA<2 and UA <4 are different in terms of dual biological effects of uric acid. Is there a difference in the width of the lowest between each paper? #4 In that sense, the dose-response analysis data is very significant. Is it possible to show the data related to CVD as a Figure (even if it is negative data)? Author had better to discuss more this dose-response impact on all-cause mortality and CVD in discussion section. #5 Figure 2 is hard to see. So, authors should increase the resolution. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0264340.r003
Revision 2
6 Feb 2022 Author Response Response to Reviewer 2: Question 1: It is interesting that there is no significant difference in the subgroup analysis (Table 1 and Table2) when adjusted with gender and diabetes, suggesting there is a difference in the impact of uric acid in these subgroups. Are such analyses possible? Or, authors should discuss on these points and data of subgroup analyses (Table 1, Table2) Answer: First, we carefully checked the variable adjustment of each included article, and ran the heterogeneity test again with Stata software, and the results were consistent with those in the manuscript (Table 2 and Table 3). Dong et al. [1] found that the associations of UA and CVD/all-cause mortality disappeared with additional adjustment for traditional CV factors such as CVD history, diabetes, BMI, and low-density lipoprotein cholesterol. This may indicate that the association between UA and CVD / all-cause mortality is not independent, but related to traditional CV risk factors in the PD population. Second, after careful consideration, we changed the subgroup analysis of whether to adjust gender into the subgroup analysis of male proportion (50% as the cut-off value). As written in paragraph 4 of the “result” section, there may be gender differences in the impact of SUA levels on mortality. Therefore, subgroup analysis based on the proportion of men may be more reasonable. We discussed the results of the subgroup analysis in lines 460-469. Question 2: Since the authors focused on all-cause mortality and CVD, it may be useful to conduct a subgroup analysis with or without obesity/visceral fat accumulation, and with or without liver dysfunction which reflects NAFLD/NASH. Is it possible that the impact of uric acid will be sharpened by doing so? Answer: Thank you for your suggestion. We conducted a subgroup analysis according to adjustment for BMI, but the results were similar to those adjusted for diabetes. After careful review of the included literature, NAFLD / NASH was not found in the comorbid conditions of the collected information. For defining NAFLD [2], there must be (1) evidence of hepatic steatosis, either by imaging or histology, and (2) lack of secondary causes of hepatic fat accumulation such as significant alcohol consumption, long-term use of a steatogenic medication, or monogenic hereditary disorders. Unfortunately, there is no data of liver imaging and histological examination in the original article. A recent meta-analysis [3] indicated that controlling the most important confounding factors, including indicators that reflect the current residual renal function of patients, and other confounding factors (including gender, age, diabetes history, CVD history, Kt/V, whether to use UA drugs and serum albumin) are very important for comparability among groups. We noticed that albumin is an index that can reflect the synthesis and reserve function of the liver in a certain period of time. Recent studies have shown NAFLD to be associated with impairments in albumin function, which are associated with impairments in liver function and disease prognosis [4]. However, we found that all studies included in this meta-analysis had adjusted for albumin, so subgroup analysis was not performed. Question 3: It will become more understandable for readers to show data on the concentration range of the uric acid category in each paper. Answer: Thank you very much for your advice. We have added concentration range of the SUA categories in Table 1. Question 4: (1) Is it possible to show the data related to CVD as a Figure (even if it is negative data)? (2) Author had better to discuss more this dose-response impact on all-cause mortality and CVD in discussion section. Answer: (1) We examined the dose-response relationship between SUA and CVD mortality and confirmed that the dose-response diagram could not be made. The P values of model goodness-of-fit tests were all < 0.05, suggesting that heterogeneity had to be considered. But neither liner (�2 = 0.84, P = 0.360, random effect linear model) nor nonlinear (�2 = 1.66, P = 0.476, random effect nonlinear model) relationship between SUA and CVD mortality was observed. The reason why there is no dose-response figure of SUA and CVD is that the random effect model is not significant, rather than the curve. Therefore, we deleted the sentence " We analyzed the linear or non-linear relationship between mortality and SUA levels, and listed only significant curves." in the “statistical analysis” part because it is very misleading. (2) Thank you very much for your advice. We added the discussion about the dose-response relationship between SUA levels and all-cause mortality. Please see lines 483-492 for details. Question 5: Figure 2 is hard to see. So, authors should increase the resolution. Answer: We have adjusted the resolution of figure2, hoping to meet the requirements of the journal. Once again, thank you very much for your comments and suggestions. Looking forward to hearing from you. Best wishes. https://doi.org/10.1371/journal.pone.0264340.r004
9 Feb 2022 Decision Letter - Masaki Mogi, Editor Serum uric acid level and all-cause and cardiovascular mortality in peritoneal dialysis patients: a systematic review and dose-response meta-analysis of cohort studies PONE-D-21-22383R2 Dear Dr. Lyu, 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, Masaki Mogi Academic Editor PLOS ONE Additional Editor Comments (optional): No further comment. 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: (No Response) ****** 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: All comments, which the reviewer had raised, have adequately addressed. The reviewer had no more question and comments. ****** 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.0264340.r005
Formally Accepted
11 Feb 2022 Acceptance Letter - Masaki Mogi, Editor PONE-D-21-22383R2 Serum uric acid level and all-cause and cardiovascular mortality in peritoneal dialysis patients: a systematic review and dose-response meta-analysis of cohort studies Dear Dr. Lyu: 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. Masaki Mogi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0264340.r006

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