Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function

Jennifer A. Hirst; José M. Ordóñez Mena; Chris A. O’Callaghan; Emma Ogburn; Clare J. Taylor; Yaling Yang; F. D. Richard Hobbs

doi:10.1371/journal.pone.0245131

Peer Review History

Original SubmissionOctober 20, 2020
19 Nov 2020 Decision Letter - Giuseppe Remuzzi, Editor PONE-D-20-32945 Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function. PLOS ONE Dear Dr. Hirst, 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 focuses on an interesting topic. The study, however, presents some important shortcomings that preclude at this stage to draw meaningful conclusions, and should be addressed. To mention few of them, i) need to describe laboratory methodology, i.e. serum creatinine assay and its traceability to IDMS and authors’ methodology for detecting raised ACR of > 3 mg/mmol; ii) unclear the authors’ sampling methodology; iii) concern about the fact that transiently impaired kidney function was not defined nor they have indicated baseline measures or the magnitude of the transient impairment; iv) need to present results with subheadings for better reading; v) need to compare authors’ data locally with national datasets as well as international registry reports like Australian, Japanese, Germany, or European CKD data, and discuss the implications in detail. Please submit your revised manuscript by Jan 03 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. 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The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Partly ******** 2. 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: No ****** 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: I congratulate the authors for such a nice study. It's important to delineate the burden of CKD and multi-morbidity at primary care level. I have few suggestions 1. The presentation of results could be sub-headings for better reading. For example if the results are presented as Overall cohort, CKD, Non CKD and Male and female. I found that there was lot of information, especially % all over the place and I moved backwards and forwards to read. 2. This data from primary care is very important and actually define a more milder cohort of CKD. If you take an average 74 year old white (98%) UK resident with hypertension, obesity and CKD as the top co-morbidities with rest of the conditions at much lower percentages including diabetes, cardiac and other vascular conditions, as seen in your data, this group represents a milder form of disease compared to any group of CKD patients seen in speciality renal practices. For example in out cohort in Australia ( 90% Caucasians) seen in specialist clinics, Obesity is >50%, Diabetes is 44%, hypertension 91%, coronary artery disease 25% and other vascular complications in the range of 10%. (https://doi.org/10.1111/nep.13567). Similar is the case in other CKD registry reports. The implications of these comparisons with other international cohorts are huge. Either you evaluated a milder form of disease or your primary care programs are working very well so much so the CKD patients are managed very well at primary care level and mulitmorbidity profile is much contained and better. I suggest that you compare your data locally with national datasets as well as international registry reports like Australian, Japanese, German or European CKD data. I think your data send a much powerful message regarding the success of primary care in your country. Reviewer #2: Thank you for the opportunity to review this paper. There are methodological issues which I believe should be addressed. One such issue you describe in your limitations (your population is not representative of the UK population and findings cannot therefore be extrapolated to the general population). You must describe laboratory methodology ie serum creatinine assay and its traceability to IDMS and your methodology for detecting a raised ACR of > 3mg/mmol. You must also describe your sampling methodology - when were blood samples taken for serum creatinine analysis, were they fasted or non-fasted (relationship to a protein containing meal); when were urine samples for ACR testing taken; were samples stored before analysis. You have not defined transiently impaired kidney function nor have you indicated baseline measures or the magnitude of the transient impairment. Although correct to say that any test has both physiological and analytical variability without detailing the conditions under which the test sample is taken, the assay used or the magnitude of the abnormal result it is impossible to draw meaningful conclusions. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Revision 1
10 Dec 2020 Author Response Reviewer #1: I congratulate the authors for such a nice study. It's important to delineate the burden of CKD and multi-morbidity at primary care level. I have few suggestions Thank you for your comments 1. The presentation of results could be sub-headings for better reading. For example if the results are presented as Overall cohort, CKD, Non CKD and Male and female. I found that there was lot of information, especially % all over the place and I moved backwards and forwards to read. We have restructured the results to findings in the full cohort from the CKD and non-CKD populations. We have also included another subheading: “Differences by GFR-estimating equation and sex” to make comparisons between the MDRD and CKD-EPI equations and males and females. 2. This data from primary care is very important and actually define a more milder cohort of CKD. If you take an average 74 year old white (98%) UK resident with hypertension, obesity and CKD as the top co-morbidities with rest of the conditions at much lower percentages including diabetes, cardiac and other vascular conditions, as seen in your data, this group represents a milder form of disease compared to any group of CKD patients seen in speciality renal practices. For example in out cohort in Australia ( 90% Caucasians) seen in specialist clinics, Obesity is >50%, Diabetes is 44%, hypertension 91%, coronary artery disease 25% and other vascular complications in the range of 10%. (https://doi.org/10.1111/nep.13567). Similar is the case in other CKD registry reports. The implications of these comparisons with other international cohorts are huge. Either you evaluated a milder form of disease or your primary care programs are working very well so much so the CKD patients are managed very well at primary care level and mulitmorbidity profile is much contained and better. I suggest that you compare your data locally with national datasets as well as international registry reports like Australian, Japanese, German or European CKD data. I think your data send a much powerful message regarding the success of primary care in your country. Thank you for your comments. We have changed the discussion to include a comparisons with literature, first in the UK followed by international settings. This section in the Discussion has now been substantially revised. Reviewer #2: Thank you for the opportunity to review this paper. There are methodological issues which I believe should be addressed.. One such issue you describe in your limitations (your population is not representative of the UK population and findings cannot therefore be extrapolated to the general population). The reviewer has pointed out a concern about the generalisability. We have compared our results with those from other studies and suggested reasons for differences in prevalence of multimorbidity and individual comorbidities. We have included a sentence to explain that we have compared with other studies: “To be transparent about the generalisability, we have discussed the results in the context of other studies, both in the UK and internationally.” You must describe laboratory methodology ie serum creatinine assay and its traceability to IDMS and your methodology for detecting a raised ACR of > 3mg/mmol. We have clarified these points in the text: “Non-fasting blood and urine samples collected at the baseline study visit were analysed within 24 hours across two laboratories using identical albumin-creatinine ratio (ACR) and isotope dilution mass spectrometry (IDMS)-traceable enzymatic creatinine assays, and reported using the Modification of Diet in Renal Disease (MDRD) eGFR. Both samples for each patient were processed in the same laboratory. The remaining 277 (32.2%) participants did not have a CKD diagnosis, but had one test with either a decreased eGFR (<60 ml/min/1.73m2) or a raised non-fasting urinary ACR (>3 mg/mmol), suggesting transiently impaired renal function, or may potentially arise from variability in analytical methods in those near diagnostic thresholds.” You must also describe your sampling methodology - when were blood samples taken for serum creatinine analysis, were they fasted or non-fasted (relationship to a protein containing meal); when were urine samples for ACR testing taken; were samples stored before analysis. Please see above You have not defined transiently impaired kidney function nor have you indicated baseline measures or the magnitude of the transient impairment. The participants we classified as having transiently impaired renal function had a single eGFR or ACR test over the diagnostic threshold, but did not meet the KDIGO criteria for sustained impairment. We have included these participants in our cohort as we believe that they may be more likely to progress to CKD than the general population. We have removed most references to transiently impaired renal function in the text and instead refer to this population as non-CKD. Details of this population, as well as other characteristics of the participants are given in a paper published earlier this year. Rather than repeat these, we have referred the reader to the paper: “More details of the population included in this analysis are given in our paper summarising the characteristics from the baseline study visit.(28)” Although correct to say that any test has both physiological and analytical variability without detailing the conditions under which the test sample is taken, the assay used or the magnitude of the abnormal result it is impossible to draw meaningful conclusions We hope the more detailed methods given above have served to clarify this. Attachments Attachment Submitted filename: Response to reviewers comments.docx https://doi.org/10.1371/journal.pone.0245131.r002
23 Dec 2020 Decision Letter - Giuseppe Remuzzi, Editor Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function. PONE-D-20-32945R1 Dear Dr. Hirst, 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. The revised manuscript is definitely improved. The authors have properly addressed all the points and comments raised by the reviewers. 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. 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If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) Reviewer #2: (No Response) ****** 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: (No Response) ****** 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: (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 #1: Thank you very much for addressing my feedback and comments. The current manuscript is definitely an improved version. I have no further comments Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Sree Krishna Venuthurupalli Reviewer #2: No https://doi.org/10.1371/journal.pone.0245131.r003
Formally Accepted
6 Jan 2021 Acceptance Letter - Giuseppe Remuzzi, Editor PONE-D-20-32945R1 Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function. Dear Dr. Hirst: 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 Prof. Giuseppe Remuzzi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0245131.r004

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