PONE-D-19-23294

Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes

PLOS ONE

Dear Mrs Teixeira,

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 a topic of potential interest. There are, however, few shortcomings in the study the authors should address. To mention few of them, i) need to expand more the conclusions; ii) need to discuss about the high rate of allograft loss and potential causes of this; iii) need to include in the method section how the cases are reviewed for the diagnosis of TMA prior to the confirmation by reviewing kidney biopsies; iv) need to include the methods of their search such as "CPT codes" used; v) need to clarify if dialysis was temporary; vi) concern about the statement that their cohort suggest risk factors for development of de novo TMA; vii) need to implement the discussion about eculizumab therapy and its use in Brazil, if any.

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

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: Line 71 and Line 510: I would change the verb "prove" to "suggest" in the conclusion. And it would be beneficial for the authors to expand more on their conclusions. They should discuss about the high rate of allograft loss and potential causes of this.

In the methods section, they should include how the cases were reviewed for the diagnosis of TMA prior to the confirmation by reviewing kidney biopsies, and include the methods of their search such as "CPT codes" used or explained how they found/ collected 119 cases with diagnosis of TMA (how was this original diagnosis made).

And this should be included as a limitation in the discussion part.

Line 248, Authors mention that over one third of patients were on dialysis, please clarify if dialysis was temporary or if there was allograft loss within the first 3 months post transplant.

Lines 446-449. Authors imply that their cohort suggest risk factors for development of de novo TMA, but without not know the primary disease of ESRD 37% on the cohort, it is hard to make a conclusion of de novo presentation. This should be clarified in this paragraph.

In the discussion, the authors should also include the lack of therapy with eculizumab in their cohort, and should recognize this drug as part of the therapy for aHUS worldwide, and perhaps disclose if this medication is not routinely used in Brazil at the moment (due to cost or other reasons, this should also be explained)

Reviewer #2: The authors have conducted a thorough retrospective review of 89 kidney transplant patients with TMA and classified their clinical and pathological findings in detail. the main observation of the study is the TMA associated with ABMR has a considerably poorer prognosis than TMA not associated with ABMR. The pathologic features did not play as large a role in differentiating outcomes with respect to dGFR.

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Reviewer #1: No

Reviewer #2: Yes: Stuart J. Knechtle

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Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes

PONE-D-19-23294R1

Dear Dr. Teixeira,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

The revised version of the manuscript is definitely improved. The authors have adequately addressed all the reviewers’ comments.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Giuseppe Remuzzi

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

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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 #1: Yes

Reviewer #2: 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 #1: Yes

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 #1: Very interesting topic. Authors have answered in detail comments made by this reviewer. I have no other comments to add at this moment.

Reviewer #2: There are several examples of words that are used incorrectly and need to be edited, but the content of the paper is excellent and the authors have responded to the reviewers' concerns.

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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

Reviewer #2: Yes: Stuart Knechtle