PONE-D-22-17930An exploration of under-registration of chronic kidney disease in Belgian general practices using logistic regression.PLOS ONE

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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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

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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

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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

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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: Van den Wyngaert et al analyzed data from the INTEGO database since 2018.

They found that the proportion of unregistered chronic kidney disease (CKD) patients was substantial. They also found that advanced stages of CKD, male, diabetes, heart failure, hypertension were associated with low risks for unregistered CKD. I have some comments about this manuscript.

1. Page 6, lines 108, Methods: In order to correctly define CKD, the calculation of eGFR should be standardized. The authors did not mention the equation that calculated eGFR. According to the KDIGO (as the reference No. 2 of this manuscript) or the KDOQI guidelines, eGFR should be calculated using the MDRD or 2009 CKD-EPI equation. A newer 2021 CKD-EPI equation has also been suggested recently.

2. Page 6, lines 108, Methods: the authors only included stages 3-5 CKD because they only include those who had an eGFR < 60 ml/min/1.73m2. This information should be more clearly described throughout the manuscript from the title, abstract, and manuscript text. Otherwise, it may cause misinterpretation that the study is providing information including the whole range of CKD patients.

3. Page 6, lines 111-112, Methods: The author used data since 2018, but did not mention the date for end of follow-up of the data.

4. Page 7, lines 127-129, Methods: This section provides almost the same information as line 107-111.

5. Page 8, lines 145-146, Methods: This description does not seem to be the calculation of "median time", should be explained more clearly. In addition, this sentence seems to provide very similar information as line 147-149.

6. Page 8, lines 160-161, Methods: The author did not mention the process of model selection for the multivariate logistic regression, and how to decide the final model as they presented in the Results section. Since the INTEGO database provided abundant information and covariates, how did author decide the inclusion and exclusion of these covariates? In addition, some of the covariates included in the multivariate model were not provided in the baseline descriptive analyses (Table 3) and some of the covariates did not have a clear definition (ex. did the covariate of diabetes include both type 1 & 2 diabetes? Did the covariate of hypertension included hypertensive kidney failure?)

7. Pages 8-9, lines 162-171, Methods: The imputation method for missing variables was not clearly described. The imputation procedure seemed to be based on unpublished data (Reference No. 22), and the detailed imputation method should be clearly and comprehensively described in the current manuscript unless this imputation method has been published. How many covariates has been imputed? What is the percentage of missing data in the study cohort? A comparison before and after imputation should be provided. The Supporting information (S1 Table. Missing data) was not provided with the submitted manuscript. In addition, what is an extra covariate?

8. Page 11, lines 223-226, Results: There seemed to be difference between registered and unregistered groups for diuretics, lipid lowering drugs, platelet aggregation inhibitors, and anticoagulants.

9. Page 11, lines 228-230, Results: the description regarding diagnosis code U99 provide duplicate information as in the Methods section (lines 117-120).

10. Table 3: There were 309 (4.3%) of unregistered CKD patients who had a diagnosis code of "Unspecified kidney disease (ICPC2 U99)" at baseline which is confusing. Please explain.

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Reviewer #1: No

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An exploration of under-registration of chronic kidney disease stages 3-5 in Belgian general practices using logistic regression.

PONE-D-22-17930R1

Dear Dr. Van den Wyngaert,

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.

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Kind regards,

Tatsuo Shimosawa, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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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

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

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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

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

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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: Early recognition of CKD and appropriate medical intervention are important in terms of reducing the number of patients with end-stage renal failure and preventing cardiovascular disease. This manuscript is valuable because it reveals a significant number of patients with CKD 3-5 whose CKD codes are not registered in the HER, indicating the importance of intervention in this patient group.

In the future, it is hoped that measures will be taken to facilitate enrollment in the HER and to provide appropriate interventions for CKD patients who are relatively unnoticed due to their lack of comorbidities.

Reviewer #3: In the present observational study, the Authors described prevalence of unregistered CKD in a Belgian General Practitioner population. Among included patients, there were 10 551 patients (5.5%) with two consecutive eGFR laboratory measurements indicating chronic kidney disease (CKD) (eGFR <60 mL/min/1.73m2), recorded at least three months apart during the baseline period. Among those patients with CKD, a significant amount (68%) did not get a diagnostic code in their Electronic Health Record (HER). Being a male, a concurrent diagnosis of diabetes, heart failure and hypertension also independently increased the possibility of a correctly registered CKD.

The Authors conclude that thinking about solutions to make it easier to register a diagnosis in the EHR is imperative.

The revised version of the paper is fairly well written, the aim is an interesting one, the methodological approach is appropriate, the results are adequately commented upon and limitations have been correctly examined.

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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.

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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

Reviewer #3: No

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