PONE-D-20-19734

Prevention of acute rejection after rescue with Belatacept by association of low-dose Tacrolimus maintenance in medically complex kidney transplant recipients with early or late graft dysfunction

PLOS ONE

Dear Dr. Biancone,

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We look forward to receiving your revised manuscript.

Kind regards,

Paolo Fiorina, MD, PhD

Academic Editor

PLOS ONE

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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

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2. In ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information.

3. Thank you for including your ethics statement:  "HUMAN RESEARCH.

The study was performed in adherence with the last version of the Helsinki Declaration and with the Principles of the Declaration of Istanbul on Organ Trafficking and

Transplant Tourism. All patients signed an informed consent before switching to Belatacept-based immunosuppressive therapy. This study is covered by Ethical

Committee approval, resolution number 1449/2019 on 11/08/2019 ("TGT" observational study)".   

Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study.

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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: The tables are very clear and the test partition is very useful for understanding the study.

For personal interest, the autors can read a work of Vikas et al. (2014), that explain the aspects of kidney transplantation in children.

Reviewer #2: The goal of this study, a suitable maintenance of immunosuppression regimen following kidney transplantations, clearly expressed in the title, is noteworthy. Nevertheless the important purpose of this work is hampered by methodological issues mainly featured by the choiche of the retrospective study method in face of a reduced sample size and without a real control group. Although the study results are consistent with the previous wider studies outcomes, these appear to be powerless. The authors are completely aware of this.

In this study relevant is the researchers interest to analyze medically complex patients otherwise excluded from the more powerfull Randomized Controlled Trials, but the worth efforts to manage highly complex patients deserve an higher patients number to provide more solid informations in this search field.

Minor issue concerns knowing more details about any other previous or concomitant immunosuppressant therapies in those patients received other organ transplants.

Finally it would be valued to obtain insights about metabolic data following belatacept therapy.

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Reviewer #1: No

Reviewer #2: No

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Prevention of acute rejection after rescue with Belatacept by association of low-dose Tacrolimus maintenance in medically complex kidney transplant recipients with early or late graft dysfunction

PONE-D-20-19734R1

Dear Dr. Biancone,

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,

Paolo Fiorina, MD, PhD

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 #1: 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

**********

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

Reviewer #1: 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 #1: Yes

**********

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

**********

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: The authors addressed all the previous comments. The manuscript can now be considered for pubblication.

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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.

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