Dear Dr. Carrero,

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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Clinical guidelines are lacking for opioid use in patients with chronic kidney disease (CKD), who have higher risks for overdose and mortality from high-dose opioid use. The authors' study found that patient data stratified by eGFR generally showed a lower risk of escalation to higher opioid doses, likely due to a more cautious approach in prescribing for patients with CKD whose renal clearance of drugs may be impaired. See my specific comments for the authors in the attached pdf file. In general ,this article may benefit from discussing more details regarding different types of pain in CKD, as well as use of non-opioid pharmacological agents and non-pharmacological strategies for pain management. Of particular interest is the potential role of dietary phosphorus restriction, often recommended in CKD, which should be investigated in future studies of pain management, especially for pain associated with CKD-bone mineral disorders.

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Kind regards,

Lalit Gupta

Academic Editor

PLOS One

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Additional Editor Comments :

Clinical guidelines are lacking for opioid use in patients with chronic kidney disease (CKD), who have higher risks for overdose and mortality from high-dose opioid use. The authors' study found that patient data stratified by eGFR generally showed a lower risk of escalation to higher opioid doses, likely due to a more cautious approach in prescribing for patients with CKD whose renal clearance of drugs may be impaired. See my specific comments for the authors in the attached pdf file. In general ,this article may benefit from discussing more details regarding different types of pain in CKD, as well as use of non-opioid pharmacological agents and non-pharmacological strategies for pain management. Of particular interest is the potential role of dietary phosphorus restriction, often recommended in CKD, which should be investigated in future studies of pain management, especially for pain associated with CKD-bone mineral disorders.

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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?

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

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Clinical guidelines are lacking for opioid use in patients with chronic kidney disease (CKD), who have higher risks for overdose and mortality from high-dose opioid use. The authors' study found that patient data stratified by eGFR generally showed a lower risk of escalation to higher opioid doses, likely due to a more cautious approach in prescribing for patients with CKD whose renal clearance of drugs may be impaired. See my specific comments for the authors in the attached pdf file. In general ,this article may benefit from discussing more details regarding different types of pain in CKD, as well as use of non-opioid pharmacological agents and non-pharmacological strategies for pain management. Of particular interest is the potential role of dietary phosphorus restriction, often recommended in CKD, which should be investigated in future studies of pain management, especially for pain associated with CKD-bone mineral disorders.

Reviewer #2: This is a well-conducted and clearly presented study addressing an important and clinically relevant question. The methodology is robust, the statistical analysis is appropriate, and the findings are interpreted in a balanced and thoughtful manner. I have no further comments and recommend acceptance in its current form.

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Reviewer #1: No

Reviewer #2: Yes: Dr. Devang Bharti

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Attachments

Attachment

Submitted filename: PONE-D-25-59036_reviewer.pdf

Patterns of opioid dose escalation in patients with chronic kidney disease initiated on opioids for the treatment of non-cancer pain

PONE-D-25-59036R1

Dear Dr. Carrero,

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,

Lalit Gupta

Academic Editor

PLOS One

Additional Editor Comments (optional):

The manuscript has been carefully revised in accordance with the thoughtful recommendations provided by the reviewers in the previous round. All concerns have been thoroughly addressed, resulting in what we believe is a significantly improved and more rigorous paper. This manuscript is now in an acceptable form and meets the high standards required for publication.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

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

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: I am satisified with the authors' revision regarding alternative pharmacological, non-pharmacological, and other therapies for pain management, including nutritional guidance recommendatios, for different types of pain in chronic kidney disease.

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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

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