International Delphi consensus on acute kidney injury: Foundations for AI-driven digital twin development in critical care nephrology

Mehdi Kashani; Jacob Ninan; Lifang Wei; Wisit Cheungpasitporn; Amos Lal; Ognjen Gajic; Kianoush Kashani

doi:10.1371/journal.pone.0344991

Peer Review History

Original SubmissionDecember 8, 2025
11 Feb 2026 Decision Letter - Chiara Lazzeri, Editor International Delphi Consensus on Acute Kidney Injury: Foundations for AI-Driven Digital Twin Development in Critical Care Nephrology PLOS One Dear Dr. Kashani, 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 Mar 28 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. 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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. [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? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: N/A Reviewer #2: Yes ****** 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 ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: This article by Kashani et. al is a DELPHI Consensus on AKI in critical care with A DAG in order to build a digital twin model for simulation. This concept is appealing, in an area of research that needs to be developed to improve simulation and teaching. The paper is well written and pleasing to read. However it lacks some detailed results on the DELPHI and a real discussion on the results itself. Minor revisions: - Line 74: all while reducing patient risk by � missing word ? - Line 110-111: The fact that you have reached consensus after two rounds belong to the results section. I would only describe your method in the method section. A maximum of three rounds planned to reach 75% agreement among experts, etc… In the result section, you can mention that agreement was achieved after 2 rounds. Same for the abstract. - Line 119: add references to support one’s statement - Line 136 : how many participants had AI related clinical initiatives ? - Line 193 to 206: please define abbreviations of biomarkers when first used in the text - Line 217: Define RBCs and AIN abbreviations - Line 222: Contrast use in CKD and AKI patients is not mentionned again in the Table 1 nor the second round of delphi. Could it be possible to give the results for AKI KDIGO III ? Which is the most frequent situation encountered in the ICU. - Line 266: please define abbreviation when first used in the text (THAM) - Line 280-285: give more details on the DAG and on its construction/logic. - Figure 3: It is hard to know what the first and second round with arrows refers to in the figure. Does that mean that consensus was obtained in the first round for the items on the left and items on the right for the second round ? - Figure 3: How did you define key biomarkers for clinical decision making ? was it a specific item of the DELPHI ? It does not appear in the Table 1 nor in the main text. - Table 1: I would add more details of the DELPHI results in the table, for each item and question. Major revisions: The paper is interesting and serves a bigger purpose. However, the discussion lacks feedback on the results of the DELPHI itself. 1- Discussion on the results: do the result of the Delphi match international recommendations ? does it match routine clinical ICU practice ? That would be particularly interesting for the biomarkers (I would be surprised if ICU routinely use NGAL Cystatin C TIMP2 IGFBP7 …) 2- Discuss the panel of experts, only 24% are intensivists, without a dual specialty in Nephrology. It really shows in the results of the Delphi. Most AKI in the regular ICU is the result of shock, which is not detailed in the paper. From a critical care perspective, the contrast use is widely used and outweighs the cons of contrast in AKI, we usually use simple biomarkers (creatinine, urea, ionogram, urinary ionogram). It is a severe limitation. Another limitation of the panel is the majority of americans experts (which is mentionned in the discussion). It could explain certain practices that seem unusual for a non-american intensivist. 3- Discuss the use of Desmopressin 4- Some part of the discussion on the relevance of a Delphi and a DAG for a digital twin is redundant, and could be shortened. Reviewer #2: Kashani et al provide their manuscript titled 'International Delphi Consensus on Acute Kidney Injury: Foundations for AI-Driven Digital Twin Development in Critical Care Nephrology'. With this Delphi the authors were able to identify key items to be used for an artificial intelligence (AI) model in patients with acute kidney injury. I think this manuscript could be of added value, although it is not possible to evaluate the AI model itself. I have some minor comments. Introduction Line 74: sentence is suddenly stopped, please revise. Methods - Line 113: could you provide a reference to substantiate this? - What is the number of experts that was approached? ****** 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: 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 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. https://doi.org/10.1371/journal.pone.0344991.r001
Revision 1
23 Feb 2026 Author Response Manuscript ID: PONE-D-25-64532 Title: International Delphi Consensus on Acute Kidney Injury: Foundations for AI-Driven Digital Twin Development in Critical Care Nephrology Dear Editor and Reviewers, We sincerely thank the Academic Editor and both reviewers for their thoughtful and constructive evaluation of our manuscript. We greatly appreciate the time and expertise invested in reviewing our work. Before addressing the reviewer comments, we confirm that we have ensured full compliance with PLOS ONE’s formatting and licensing requirements. Specifically: • Documentation confirming licensing compliance for Figure 2 has been uploaded with this revision. • All institutional and platform logos have been removed from the Supporting Information files to comply with CC BY 4.0 policies. • Table 1 is now appropriately cited in the manuscript text. • The manuscript has been formatted according to PLOS ONE guidelines. • All major and minor revisions are clearly highlighted in red in the revised manuscript. Response to the Academic Editor In response to the Editor’s request to strengthen the discussion of the Delphi results, we have substantially revised and expanded the Discussion section. Specifically, we have: • Provided deeper contextualization of the Delphi findings relative to international recommendations and routine ICU practices. • Clarified the translational gap between biomarker endorsement and real-world ICU implementation. • Expanded discussion of contrast use in AKI, desmopressin practices, and the influence of panel composition (including subspecialty distribution and geographic representation). • Streamlined redundant sections related to the Delphi–DAG–digital twin framework to improve clarity and focus. All supplementary information regarding the figures are uploaded. This study is based on a Delphi process which is survey of experts anonymously. We did not include any patient information and all data from the surveys are already available in the manuscript. Response to Reviewer #1 We thank Reviewer #1 for the positive evaluation of the scientific rigor and conceptual importance of our work. All minor comments have been addressed, including 1) correction of the incomplete sentence in the Introduction section, 2) clarification of the Delphi methodology by separating planned design from achieved results, 3) addition of methodological references supporting the consensus threshold, 4) definition of all abbreviations at first use, 5) clarification of biomarker terminology, 6) expanded reporting of KDIGO stage III findings, 7) definition of THAM, and 8) detailed description of the DAG construction process. Figure 3 has been revised for clarity, and the figure legend has been updated to explicitly explain the framework and avoid confusion regarding round-specific arrows and biomarker categorization. Table 1 has been expanded to provide detailed round-by-round results, including agreement percentages and consensus status. In response to the major comments, we substantially revised the Discussion section to critically analyze the Delphi findings, compare them with international recommendations and routine ICU practice, discuss limitations related to panel composition and geographic predominance, explicitly address desmopressin use, and reduce redundancy in the discussion of the digital twin conceptual framework. Response to Reviewer #2 We thank Reviewer #2 for the positive assessment of the manuscript’s scientific validity. We corrected the incomplete sentence in the Introduction section, added appropriate methodological references, and clarified the total number of experts invited and participating in the Delphi process. We believe these revisions have substantially strengthened the manuscript’s clarity, methodological transparency, and clinical contextualization. We are grateful to the reviewers for their insightful comments, which have significantly improved the rigor and presentation of our work. Sincerely, Kianoush B. Kashani, MD, MS Corresponding Author On behalf of all authors Attachments Attachment Submitted filename: Reviewers response.docx https://doi.org/10.1371/journal.pone.0344991.r002
2 Mar 2026 Decision Letter - Chiara Lazzeri, Editor International Delphi Consensus on Acute Kidney Injury: Foundations for AI-Driven Digital Twin Development in Critical Care Nephrology PONE-D-25-64532R1 Dear Dr. Kashani, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- 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. Kind regards, Chiara Lazzeri Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0344991.r003
Formally Accepted
Acceptance Letter - Chiara Lazzeri, Editor PONE-D-25-64532R1 PLOS One Dear Dr. Kashani, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Chiara Lazzeri Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0344991.r004

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