Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

PONE-D-19-30433

Acute Kidney injury among neonates in a tertiary hospital in Tanzania; prevalence, risk factors and outcome

PLOS ONE

Dear Dr Francis F Furia,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that the manuscript has merit but, at in its present form, does not fully meet PLOS ONE’s publication criteria . Therefore, after consideration of Reviewer 1 points, we invite you to submit a revised version of the manuscript that addresses each of the points raised during the review process.

ACADEMIC EDITOR: :

• Could you address each of the points individually and return a marked up copy
• The manuscript has merit because of the rarity of the information. if you are able to answer each point, we'd like to see a revised version. i agree with the points raised through the excellent review provided below

We would appreciate receiving your revised manuscript by 14/01/2020. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

David S Gardner

Academic Editor

PLOS ONE

Journal Requirements:

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 http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please amend either the title on the online submission form (via Edit Submission) or the title in the manuscript so that they are identical.

3. Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately.  These will be automatically included in the reviewers’ PDF.

Additional Editor Comments (if provided):

[Note: HTML markup is below. Please do not edit.]

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

**********

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

Reviewer #1: Yes

**********

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

**********

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

**********

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: This manuscript provides the prevalence, risk factors and outcomes of acute kidney injury among 378 critically ill neonates in a single center tertiary hospital in Tanzania. The authors should be commended for this extensive research undertaking in setting of a resource limited setting. The data presented would be improving upon the available epidemiological literature on neonatal acute kidney injury in East Africa. The ultrasound findings should be further highlighted in this manuscript given that the literature on this topic is rather sparse in developing countries. While the data presented is unique, there are certain points that need to be clarified especially regarding the research methodology, which are delineated below:

Major points:

-To strengthen the introduction, the second paragraph could include what the average international estimated prevalence of AKI is and what is known about neonatal AKI in developing countries with similar limited facilities. Alternatively, the authors may indicate how neonatal rates of mortality from asphyxia, prematurity and sepsis differ in Tanzania compared to global outcomes to provide better context for the manuscript findings.

- Page 4, Line 76-78: “All critically ill neonates admitted in neonatal ward presenting with convulsion, altered level of consciousness, inability to feed, vomiting everything, respiratory distress, jaundice, hyper/hypothermia, dehydration and shock were eligible for this study.” Is it necessary to specify all diagnosis included if the only those with obvious congenital abnormalities of GU tract were excluded? Were there other diagnoses that were excluded?

- Page 4, Line 82-83: “Sample size was estimated using prevalence of AKI (33.3%) reported among admitted 83 neonates in Zimbabwe by Matyanga et al. [12]” Explain how this reference was used to determine sample size for this cross-sectional study.

- Please specify if there were any missing data especially surrounding creatinine. Please specify whether AKI definition was comparing just baseline + 48 hours after admission creatinine in the methods. In general, KDIGO guidelines recommend serum creatinine rise 1.5X baseline within 7 days but creatinine at 7 days did not seem to be included in the study. There also seems to be missing data regarding participants who got KUB Ultrasounds (74+14(died) = 88, but 119 had AKI).

- Indicate in results that no patients were on dialysis.

- Please specify how neonatal sepsis is defined? Should it be neonatal bacteremia instead? In generally, neonatal sepsis could occur from pneumonia, meningitis, etc. Where those with severe pneumonia and meningitis also considered to have neonatal sepsis?

- Specify whether team focused on only in-hospital death.

- Page 15, Line 210-214: “The diagnosis of AKI was established by measuring serum creatinine at baseline and 48 hours after admission” should be included in the methods.

- The authors may want to highlight the amount of congenital abnormalities observed among those with AKI in abstract detected via ultrasound and how it relates to global rates in the discussion.

-Fig 1: Please indicate the distribution of AKI stages

-Fig 2: Consider cleaning up the legend and consider 3 vertical box + whiskers plots to display the distribution of baseline, 72 hour and 14 day creatinine values for all patients to present the data more succinctly.

- The discussion seems to indicate what is consistent in this study with prior data but it would be better if it could also highlight what is different regarding these findings compared to prior findings and reasons for the differences.

- The authors may consider adding the following: A large limitation of this study is that the Muhimbili National Hospital appears to be a secondary/tertiary referral hospital, which likely would lead to overestimation of the prevalence of neonatal acute kidney injury.

Minor points:

- Page 3, Line 52: 0 by 25 Initiative is to eliminate preventable deaths from AKI worldwide by 2025.

- Minor inconsistencies regarding whether MNH is a secondary or tertiary referral hospital.

- Page 7, Line 137-138: Consider: “A total of 378 neonates were enrolled in this study, of which 81% (306/378) were ≤ 7 days in age and 59.8% were male (226/378).”

- Page 7, Line 139: Consider: “Majority of the participants were full term (78.0%), had birth weight above 2500 grams (74.3%) and a five-minute Apgar score above 7 (82.5%).”

- Table 2: define RDS and HIE

- Page 11, Line 189-191: Table 4 describes the outcome of study participants, the overall mortality in this study was 22.5% (85/378), and participants with AKI had significantly higher mortality (70.6%) as compared to those without AKI (29.4%) p value of 0.000� P- value should be < 0.01?

- Page 12, line 204- Missing period

- Page 13, Line 224 and 225: missing comma

- Page 13, Line 229: clinicians

-Page 14, Line 228: missing period

**********

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

[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 be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

Acute Kidney injury among critically ill neonates in a tertiary Hospital in Tanzania; prevalence, risk factors and outcome

PONE-D-19-30433R1

Dear Dr. Furia,

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.

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.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

David S Gardner

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

i am happy that all comments have been addressed to a rigorous review and that the information in the manuscript adds new information to the literature on AKI in neonates

Reviewers' comments: