-->PONE-D-25-64299-->-->Precision Immunosuppression and Long-Term Kidney Transplant Outcomes: A Dual Survival Modeling Framework-->-->PLOS One

Dear Dr. Apanisile,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Rajendra Bhimma, PhD

Academic Editor

PLOS One

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Additional Editor Comments:

Thank you for the opportunity to review this manuscript on "Precision Immunosuppression and Long-Term Kidney Transplant Outcomes: A Dual Survival Modeling Framework"

The reviewers have made a few comments that need to be addressed. In addition these comments should be addressed.

1. The imputation strategy—particularly imputing missing cPRA values as zero with a binary indicator—may introduce bias and should be more explicitly justified.

2. While the authors appropriately use multivariable adjustment, the conclusions regarding “protective” or “beneficial” effects of specific induction and maintenance regimens are sometimes phrased too strongly for a retrospective registry-based analysis. Confounding by indication (e.g., sicker or higher-immunologic-risk patients preferentially receiving ATG or steroid-sparing regimens) is not adequately addressed. Consideration of sensitivity analyses (e.g., propensity-based methods) or clearer acknowledgement of this limitation would strengthen the work.

3. The study spans more than two decades (2000–2024), during which transplant practices, immunosuppressive protocols, allocation systems, and outcomes have changed substantially. Although the sample size is impressive, the lack of explicit adjustment for transplant era or policy changes (e.g., allocation system revisions) is a concern and may affect the interpretation of long-term outcomes.

4. The findings regarding racial and ethnic differences, donor race effects, and induction regimen combinations (e.g., ATG + IL-2R) are potentially sensitive and clinically important. These results merit more cautious interpretation and contextualization to avoid overinterpretation of registry-based associations.

5. Please update terminology in line with the lastest ISN guidelines - see Am J Transplant. 2021;21:901–902.

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

Reviewer #2: 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

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: very well done. complete and important.great topic. good stats.this is a thorough review of the existing literature and an excellent statistical analysis of multiple regimens and patients with complex characteristics

Reviewer #2: Thanks for giving the opportunity to review article titled “Precision Immunosuppression and Long-Term Kidney Transplant Outcomes: A Dual Survival Modeling Framework.”

I have following queries/comments:

- Although the title talks about the precision immunosuppression there is no mention of use of pharmacometrics, genetic testing (e.g., CYP3A5) or any biomarkers to achieve superior graft/patient outcome. Suggest changing the title and removing precision immunosuppression from it

- Line no.222- 5 year death censored graft survival is mentioned 80% but it is mentioned 75.8% at 4 years median (table 1). Please explain the discrepancy

- What was the difference between KDPI of DCD vs non-DCD donors

- Please provide details of incompatible transplants in each group

- Combination therapy with ATG and IL2R had worst graft survival. What could be the reason for this?

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-->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: Yes: DR. PRANAW KUMAR JHA

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

-->PONE-D-25-64299R1-->-->Immunosuppressive regimens and long-term kidney transplant outcomes: a dual survival modelling framework -->-->PLOS One

Dear Dr. Apanisile,

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 Jun 15 2026 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 letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labelled '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 labelled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labelled '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.

As the corresponding author, your ORCID ID is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only  the individual author can complete the verification step; PLOS staff cannot  verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

Rajendra Bhimma, PhD

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Additional Editor Comments:

Thank you for the opportunity to review your manuscript "Immunosuppressive regimens and long-term kidney transplant outcomes: a dual survival modelling framework ” (PONE-D-25-64299R1)". The manuscript has been reviewed by two other reviewers as well. Please see the comments by reviewers.

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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

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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

**********

-->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: No

**********

-->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

**********

-->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 the queries raised have been answered satisfactorily and the manuscript appears to be better now after the necessary modifications

**********

-->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: Yes: Dr.Pranaw Kumar Jha

**********

[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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Immunosuppressive regimens and long-term kidney transplant outcomes: a dual survival modeling framework

PONE-D-25-64299R2

Dear Dr. Kunle Apanisile

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,

Rajendra Bhimma, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Dear Dr Kunle Apanisile,

Thank you for your revisions of the manuscript "Immunosuppressive regimens and long-term kidney transplant outcomes: a dual survival modeling framework ". All comments raised by the reviewers have been adequately addressed.

Reviewers' comments: