Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis

Esther M. Nasuuna; Nicholus Nanyeenya; Davis Kibirige; Jonathan Izudi; Chido Dziva Chikwari; Robert Kalyesubula; Barbara Castelnuovo; Laurie A. Tomlinson; Helen A. Weiss

doi:10.1371/journal.pone.0301954

Peer Review History

Original SubmissionMarch 25, 2024
25 Mar 2024 Author Response Attachments Attachment Submitted filename: Response to reviewers summary.docx https://doi.org/10.1371/journal.pone.0301954.r001
27 May 2024 Decision Letter - Udeme Ekpenyong Ekrikpo, Editor PONE-D-24-11592Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis.PLOS ONE Dear Dr. Nasuuna, 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 Jul 11 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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EN, Doctoral Research Fellow, NIHR131273 is funded by the NIHR for this research project. The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The author(s) received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Additional Editor Comments: 1. The authors should pay attention to the poor formatting of all in-text citations. Please ensure proport formatting using the PLOS ONE citation style. 2. The primary weakness of this manuscript is the authors' failure to use a standard definition for CKD as prescribed by KDIGO. The included studies utilized varying definitions of kidney dysfunction from dipstick proteinuria of at least +1, albumin-creatinine ratio and varying cut-off of eGFR. Also, it appears the cross-sectional studies reported single measures of eGFR and/or ACR. This makes it possible that individuals with AKI were included in this analysis and wrongly classified as CKD. The authors can circumvent this by including a sub-group meta-analysis of studies that employed the strict KDIGO definition of CKD. 3. Please report a sub-group analysis comparing the kidney dysfunction prevalence in the ARV-naive compared to the ARV-exposed population. 4. 13/16 (81.3%) and not the reported 86.7% of studies were cross-sectional. [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: Partly Reviewer #2: Partly Reviewer #3: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 definition of CKD used lacked standardization, hence the likelihood for inclusion of non-CKD and AKI cases. Also why was the study that used UNGAL included, as it doesn't differentiate CKD from AKI. Reviewer #2: All the included articles in this study did not use the standard definition of CKD. This makes the validity of the study doubtful based on the primary objective of the study. I also acknowledged that this was stated as a limitation. The authors may consider to include only articles that used the standard definition of CKD or may change the description of their study population from CKD to a term that will reflect the population included in this study which is not strictly CKD population Reviewer #3: The topic is challenging but should using the standard CKD definition eGFR < 60 ml/min/1.73m with marker of kidney damage for 3 months or more to choose the eligible studies. line 35 wrong YPHLIV abbreviation, line 43 wrong %, line 80 phosphaturia not a marker and need to rewrite the whole sentence in proper way. line 83 should include Africa %. line 90 need to rewrite the whole sentence in proper way. line 98 mention the extend of higher risk (fold). box 1 use the original reference of KDIGO. line 190 IOM Abb. came late. line 195 "fulfilled the inclusion criteria" wrongly used as the 802 not fulfilled the criteria. line 253 using or not proper the same Abb. Table 2 title sample size (4th sector) is wrong. line 299 the funnel plot shows Asymmetry and Egger test is not sig. should use the Pegg test. line 352 albumin not used to diagnose CKD should be Albuminuria. In the whole manuscript there are Invalid: - format of the references - full stop after the Headings - using comma in 95% CI range ****** 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 Reviewer #3: 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.0301954.r002
Revision 1
17 Jun 2024 Author Response Response to editor and reviewers. Author comment I thank the editor and the reviewers for the considered comments that have greatly improved this paper. The editor and the reviewers highlight an important point about the papers that were included in the systematic review not following the standard definition of CKD as recommended by KDIGO. Although, we found only one paper that followed the strict KDIGO criteria of GFR <60ml/min/1.73m2, we still found it prudent to report the broader results of the comprehensive systematic review to show that there is very limited research and what has been done does not follow the gold-standard definitions of CKD. Thus there is a substantial evidence gap regarding kidney health among young people living with HIV in Africa. Given the prevalence of HIV on the continent and the young median age of the population of many countries in Africa this is a critical area to understand the potential future burden of CKD. 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 Response: The manuscript has been formatted according to the templates above. 2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. The American Journal Experts (AJE) (https://www.aje.com/) is one such service that has extensive experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. Please note that having the manuscript copyedited by AJE or any other editing services does not guarantee selection for peer review or acceptance for publication. Upon resubmission, please provide the following: The name of the colleague or the details of the professional service that edited your manuscript Response: The colleague that edited my manuscript is Helen Weiss. A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a supporting information file) A clean copy of the edited manuscript (uploaded as the new manuscript file) 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: “The authors would like to acknowledge James Prior for the support to EMN and the Librarian at LSHTM, Kate Perris who helped with the development and review of the search terms. Support for research was provided by Fogarty International Centre, National Institutes of Health (grant #2D43TW009771-06) HIV and co-infections in Uganda. HAW is funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement (Grant Ref: MR/R010161/1). EN, Doctoral Research Fellow, NIHR131273 is funded by the NIHR for this research project. The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The author(s) received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: All funding-related information has been removed from the acknowledgements section. The cover letter has a section with funding statement for the revision. Additional Editor Comments: 1. The authors should pay attention to the poor formatting of all in-text citations. Please ensure proport formatting using the PLOS ONE citation style. Response: The references have been formatted as per the PloS One citation style. 2. The primary weakness of this manuscript is the authors' failure to use a standard definition for CKD as prescribed by KDIGO. The included studies utilized varying definitions of kidney dysfunction from dipstick proteinuria of at least +1, albumin-creatinine ratio and varying cut-off of eGFR. Also, it appears the cross-sectional studies reported single measures of eGFR and/or ACR. This makes it possible that individuals with AKI were included in this analysis and wrongly classified as CKD. The authors can circumvent this by including a sub-group meta-analysis of studies that employed the strict KDIGO definition of CKD. Response: Of the four studies that had repeated measurements of GFR, only one (Zimba 2016) followed the strict KDIGO definition of CKD of GFR<60ml/min/1.73m2 repeated after 3 months. Tadesse 2019 used a definition of <90ml/min/1.73m2 and Byers 2023 used a definition of <90ml/min/1.73m2. Mosten 2015 diagnosed CKD using albuminuria and repeated the urinalysis after only one month. It is, therefore, unfortunately not possible to do a meaningful subgroup analysis. 3. Please report a sub-group analysis comparing the kidney dysfunction prevalence in the ARV-naive compared to the ARV-exposed population. Response: This is provided in Table 2 at the top of page 12. 4. 13/16 (81.3%) and not the reported 86.7% of studies were cross-sectional. Response: We thank the reviewer for this correction. This has been changed on line 43 Comments to the Author 5. Review Comments to the Author Reviewer #1: The definition of CKD used lacked standardization, hence the likelihood for inclusion of non-CKD and AKI cases. Also why was the study that used UNGAL included, as it doesn't differentiate CKD from AKI. Response: Thank you for this observation. As the reviewer rightly states, the studies used different definitions to diagnose CKD in their populations. We have stated that only one following the KDIGO recommended definition in the results (line 67-68). In the Discussion (lines 354-356), we explain that UNGAL is one of the newer biomarkers that might be able to help diagnose kidney dysfunction earlier than the traditionally used ones. Line 351-352. Although this study did not use creatinine based GFR, we chose to show what has been done to show kidney function among YPLHIV in SSA and it was better to be more inclusive than exclusive. However, in this study (as in the other 12 studies), they did not repeat the measurements to determine chronicity. We include this as a major limitation in this study. Reviewer #2: All the included articles in this study did not use the standard definition of CKD. This makes the validity of the study doubtful based on the primary objective of the study. I also acknowledged that this was stated as a limitation. The authors may consider to include only articles that used the standard definition of CKD or may change the description of their study population from CKD to a term that will reflect the population included in this study which is not strictly CKD population Response: We thank you for this comment, this concern has been addressed in the author comment at the top of page 1 in this response to reviewer comment. Reviewer #3: The topic is challenging but should using the standard CKD definition eGFR < 60 ml/min/1.73m with marker of kidney damage for 3 months or more to choose the eligible studies. Response: Thank you for this suggestion. The reasons for not following the standard definition of CKD have been discussed in the author comments above. line 35 wrong YPHLIV abbreviation, Response: Thank you for picking this up. This has been corrected. Line 35 line 43 wrong %, Response: Thank you for bringing this to our attention. This has been corrected. Line 43 line 80 phosphaturia not a marker and need to rewrite the whole sentence in proper way. Response: Thank you for this comment. Phosphaturia has been removed as a marker of kidney damage. Line 75 line 83 should include Africa %. Response: Thank you for the suggestion. The prevalence of CKD in Sub-Saharan Africa has been added. Lines 78-79. line 90 need to rewrite the whole sentence in proper way. Response: Thank you for picking this up. This has been rewritten. Lines 85 to 86 line 98 mention the extend of higher risk (fold). Response: Thank you for the suggestion. A fourfold higher risk of kidney disease has been added. Lines 92. box 1 use the original reference of KDIGO. Response: Thank you. The original reference of KDIGO has been added to the box (Reference 1, Box 1, fourth line). line 190 IOM Abb. came late. Response: Thank you for bringing this to our attention. We have removed this abbreviation (line 178) line 195 "fulfilled the inclusion criteria" wrongly used as the 802 not fulfilled the criteria. Response: Thank you. We have reworded this to indicate articles that fulfilled the search criteria (lines 184 to 185). line 253 using or not proper the same Abb. Response: Thank you. We have corrected this (line 222). Table 2 title sample size (4th sector) is wrong. Response: Thank you for noticing this. This has been changed to population in Table 2. line 299 the funnel plot shows Asymmetry and Egger test is not sig. should use the Pegg test. Response: Thank you for the suggestion. The funnel plot may look asymmetrical, but it is not very conclusive to determine if there is publication bias simply by looking at the funnel plot especially if the review has few studies as in this case. The Begg test in this analysis showed a p value of 0.03 but we think publication bias is unlikely given the substantial heterogeneity of the studies in this review, and prefer to retain the Egger test as it has been shown to be more accurate (1).” line 352 albumin not used to diagnose CKD should be Albuminuria. Response: Thank you for bringing this to our attention. We have changed this to albuminuria (line 318). In the whole manuscript there are Invalid: Thank you for pointing these out. They have been addressed as shown below. - format of the references: These have been reformatted throughout the manuscript. - full stop after the Headings: All full stops have been removed from the headings. - using comma in 95% CI range: All commas have been removed from the 95% CI range References 1. Shi X, Nie C, Shi S, Wang T, Yang H, Zhou Y, et al. Effect comparison between Egger’s test and Begg’s test in publication bias diagnosis in meta-analyses: evidence from a pilot survey. Int J Res Stud Biosci. 2017;5(5):14-20. Attachments Attachment Submitted filename: 20240617 Response to reviewers and editor Final.docx https://doi.org/10.1371/journal.pone.0301954.r003
29 Jul 2024 Decision Letter - Udeme Ekpenyong Ekrikpo, Editor PONE-D-24-11592R1Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis.PLOS ONE Dear Dr. Nasuuna, 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 author's response to the reviewer's comments is noted. The limitations of this manuscript are also well noted. Please do the following and re-submit the manuscript. 1. Please remove the urinary NGAL study from the list of articles included, as suggested by one of the reviewers. Using an NGAL study simultaneously with creatinine-based GFR does not appear appropriate. Repeat the analysis without the NGAL study. Of course, the NGAL study can be referenced in the discussion section while highlighting the need for early CKD diagnosis. 2. Kindly convert Appendix 4 from EXCEL to MS Word format and resubmit. Please submit your revised manuscript by Sep 12 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. 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, Udeme Ekpenyong Ekrikpo, MBBS PhD Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0301954.r004
Revision 2
31 Jul 2024 Author Response Please do the following and re-submit the manuscript. 1. Please remove the urinary NGAL study from the list of articles included, as suggested by one of the reviewers. Using an NGAL study simultaneously with creatinine-based GFR does not appear appropriate. Repeat the analysis without the NGAL study. Of course, the NGAL study can be referenced in the discussion section while highlighting the need for early CKD diagnosis. Response: the NGAL paper has been removed from the analysis. The systematic review now includes 15 and not 16 papers. This has been reflected in all tables, figures and in the text. See attached manuscript. 2. Kindly convert Appendix 4 from EXCEL to MS Word format and resubmit Response: Appendix 4 has been converted to word and is attached as a word document. Attachments Attachment Submitted filename: Response to reviewers July 2024.docx https://doi.org/10.1371/journal.pone.0301954.r005
7 Aug 2024 Decision Letter - Udeme Ekpenyong Ekrikpo, Editor Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis. PONE-D-24-11592R2 Dear Dr. Nasuuna 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, Udeme Ekpenyong Ekrikpo, MBBS PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0301954.r006
Formally Accepted
16 Aug 2024 Acceptance Letter - Udeme Ekpenyong Ekrikpo, Editor PONE-D-24-11592R2 PLOS ONE Dear Dr. Nasuuna, 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 Associate Professor Udeme Ekpenyong Ekrikpo Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0301954.r007

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