PONE-D-22-17476Association of Ideal Cardiovascular Health Metrics with Incident Chronic Kidney Disease: more than a decade follow-up in the Tehran Lipid and Glucose Study (TLGS)PLOS ONE

Dear Dr. tohidi,

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2. We note that your study is based on the clinical trials described in the references 20 and 21. Please provide the clinical trial registration numbers for these trials in your manuscript.

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Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: 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: Alizadeh and colleagues carried out a prospective study examining the association between ideal cardiovascular health metrics and incident chronic kidney disease. In a cohort of 7388 patients, they found that ideal and intermediate categories of BMI, BP and ideal categories of FBP are associated with lower risk of incident CKD in middle-aged subjects while only intermediate and ideal categories of BP associated with lower CKD risk.

This manuscript could be of some interest, but I have several concerns. Briefly, my comments:

1) In the Abstract the following sentence needs to be rephrased because there are not only HR but also the percentage of risk reduction “the corresponding HRs (95% confidence intervals) were 13% (0.87, 0.77-0.99), 16% (0.84, 0.76-0.99), 21% (0.79, 0.68-0.93), 30% (0.70, 0.60-0.83) and 24% (0.76, 0.64-0.91)”. Furthermore, in the conclusion of abstract Authors stated that Results were found only in middle-aged while there are some findings also in elderly subjects. Abstract needs to be improved

2) In Methods Section, Authors indicated that at baseline in TLGS were excluded subjects without CKD, but definition of this disease is not only based on GFR but also urinary anomalies such as proteinuria and albuminuria. Could Authors exclude that, at baseline, patients had a significant proteinuria? This is a crucial point in the evaluation of incident CKD. If data on proteinuria were not available, I suggest referring to low eGFR (<60 ml/min) as outcome instead of CKD.

3) Creatinine levels were assessed by kinetic colorimetric Jaffè and not with enzymatic assay, but CKD-EPI formula was used to estimate GFR. The Authors did not perform a correction on creatinine values to use CKD-EPI formula. This could limit GFR evaluation. I suggest that Since creatinine was not standardized to isotope dilution mass spectrometry values, Authors could reduce creatinine values by 5% as indicated by Skali et al. and, after, could use CKD-EPI formula (PMID: 21884875)

4) Surprisingly, 68.3% of elderly subjects (>65 y) enrolled in the study developed incident CKD. I think that a selection bias could be the reason for this high incidence of CKD. Probably, Authors could limit the analyses on middle-aged population.

Reviewer #2: I’ve read with interest the draft “Association of ideal cardiovascular health metrics with incident chronic 2 kidney disease: more than a decade follow-up in the Tehran Lipid and 3 Glucose Study (TLGS)”, by Fatemeh Alizadeh, Maryam Tohidi, Mitra Hasheminia, Firoozeh Hosseini-Esfahani, Fereidoun Azizi, Farzad Hadaegh

However, some important issues have to be raised.

Introduction:

- Line 46-47. Authors should briefly introduce and define the main non-communicable diseases (NCDs).

- Line 65-66. A multifactorial treatment aimed at multiple risk factors reduces the risk of cardiovascular events in populations with type 2 diabetes mellitus and renal impairment. This issue is addressed in some recent literature which should be added to the references. Gaede P et al, N Engl J Med. 2003;348(5):383-393. doi:10.1056/NEJMoa021778; Sasso FC et al Cardiovasc Diabetol. 2021;20(1):145. Published 2021 Jul 16. doi:10.1186/s12933-021-01343-1

Methods and Materials:

- Line 128-129. Font typing error.

Discussion:

- Line 251. “china” is a typing error.

- Line 237-239. “Among middle-aged participants, the intermediate and ideal categories of BMI and BP, and the ideal category of FPG and in elderly individuals, only intermediate and ideal BP was associated with reduced risk of CKD”. The authors should better clarify the pathophysiological mechanisms/hypotheses supporting this sentence.

- Line 262. “Actually, no association was demonstrated between ICVHM and incident CKD among elder population”. It therefore seems that ICVHM does not affect the prognosis of elderly patients. However, some recent literature seems in contrast with this conclusion. The authors should better clarify the pathophysiological mechanisms/hypotheses supporting this sentence.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-22-17476R1Association of ideal cardiovascular health metrics with incident low estimated glomerular filtration rate: more than a decade follow-up in the Tehran Lipid and Glucose Study (TLGS)​PLOS ONE

Dear Dr. tohidi,

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:In particular, the authors have to address the issues raised by the third reviewer.

Please submit your revised manuscript by 2 weeks. 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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• 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,

Ferdinando Carlo Sasso, PhD, MD

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Please, address the issues raised by reviewer 2 and 3.

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Reviewers' comments:

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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)

Reviewer #3: (No Response)

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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 #1: All the criticisms raised were solved by the Authors. I do not have any further comment on the manuscript.

Reviewer #2: Dear Editor,

I’ve re revised the paper “Association of ideal cardiovascular health metrics with incident low estimated

glomerular filtration rate: more than a decade follow-up in the Tehran Lipid and

Glucose Study (TLGS)”, by Fatemeh Alizadeh et al.

However, some important issues need to be raised.

- Some drugs seem to have a beneficial effect on patients with chronic kidney disease. Please, briefly discuss this point by adding the reference (Irbesartan reduces the albumin excretion rate in microalbuminuric type 2 diabetic patients independently of hypertension: A randomized double-blind placebo-controlled crossover study. DOI 10.2337/diacare.25.11.19)

- The role of drugs as potential cofounders was not discussed. Please, briefly discuss this important issue.

Reviewer #3: PONE-D-22-17476R1: statistical review

SUMMARY. This is a cohort study to evaluate the association between ideal cardiovascular health metrics (ICVHM) and time up an event of low estimated glomerular filtration rate (eGFR). The core statistical analysis relies on a battery of Cox regression models where the effect of ICVHM is adjusted by including available confounding factors. I have several concerns about the estimation method (major issue 1), sample selection (major issue 2), model specification (major issue 3). I also append some specific points that should be addressed.

MAJOR ISSUES.

1. Lines 178-180. Although data are interval censored, event times are estimated by mid-points and treated as they were exact times. This approach is a potential source of bias and it is not correct. The authors should repeat the statistical analysis by accounting for the additional uncertainty brought by interval censoring. Cox regression analysis for interval-censored data can be easily perfromed in Stata, which is the software exploited by the authors: see the command "stintcox".

2. Lines 91-97. The statistical analysis is made on a subset of the initial sample. To avoid issues of selection bias, the authors should explain why the final sample can be considered as a random subset of the initial sample. See also specific point 1 below.

3. If I have understood well, covariates are included at baseline. However, some of this covariates (e.g. age) are time-varying and certainly have a time-varying confounding effects on the time up to the event. I'd welcome an analysis that adjusts for time-varying covariates. Alternately, the authors should explain why time-varying covariates are not appropriate here.

SPECIFIC POINTS

1. In lines 77-81, the authors talk about a large population-based study conducted in the Middle East and North Africa (MENA) during more than 15 years of follow-up. In lines 84-89, they instead talk about a 3-year study in Teheran, which seems the study considered in this paper. What is the link between the two studies? Why was the large population 15-year study evoked, if the actual study of interest is the 3-year study? Please clarify.

2. Lines 182-184. I'm glad that the authors have made some diagnostics of the model. However, the results are declared but not displayed. These secondary results should be commented and displayed as supplementary material.

3. Data. It is good that all the data are available without restrictions in a repository. However, is this repository public? If it is not, then the authors should provide precise instructions for obtaining the data.

4. There is a tendency to interpret the results as they were the outcome of a logistic regression model where the dependent variable is a binary variable that records the occurrence of the event. However, the dependent variable in a Cox model is the time up to the event and covariates modulate the hazard function. The text should be modified accordingly.

5. There some typos across the text, please check.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Association of ideal cardiovascular health metrics with incident low estimated glomerular filtration rate: more than a decade follow-up in the Tehran Lipid and Glucose Study (TLGS)​

PONE-D-22-17476R2

Dear Dr. tohidi,

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,

Ferdinando Carlo Sasso, PhD, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No further comments

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: 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 #1: Yes

Reviewer #2: Yes

Reviewer #3: (No Response)

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: (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: Yes

Reviewer #3: (No Response)

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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 #1: Yes

Reviewer #2: Yes

Reviewer #3: (No Response)

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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 #1: All the criticisms raised were solved by the Authors. I have no further comment to do on the manuscript.

Reviewer #2: (No Response)

Reviewer #3: (No Response)

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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