All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
Thank you for your careful and thoughtful revisions. Both reviewers have confirmed that the revised manuscript has addressed all previously raised concerns satisfactorily. Reviewer 1 highlighted significant improvements in the title, abstract, introduction, and methodological clarity, particularly the inclusion of appropriate AKI definitions and a well-described mediation analysis framework.
The discussion and conclusion now align well with the presented data and emphasize the clinical relevance of PLR as a prognostic marker. Reviewer 2 also expressed satisfaction with your revision and had no further queries or concerns.
Based on this positive evaluation, I am pleased to confirm that your manuscript is accepted for publication. Congratulations on your excellent work.
Title & Abstract
The revised title is now precise and accurately reflects the study's data sources, avoiding any misinterpretation.
The results section of the abstract is significantly improved and readers are given clear, actionable data. No further changes are suggested.
Introduction
The introduction is now thorough and has been greatly expanded. The additional paragraphs on the pathophysiological justification for PLR cover the immunomodulatory function of platelets and the importance of lymphopenia in sepsis and then the comparison with other indices, such as NLR makes a strong case for the particular study of PLR. No further changes are suggested.
Figures & Tables
The tables and figures are clear, legible and free from unnecessary modification.
Material and Methods
The main methodological issues have been resolved by the revisions. The AKI definition now appropriately incorporates both serum creatinine and urine output criteria. The analytical approach is now more credible and reproducible. The statistical framework, software and metrics utilized in the mediation analysis are now adequately described. No further changes are suggested.
Results
One significant strength of this study is that it is among the first to examine this trajectory for PLR in a septic AKI population. The revised version of results appear complete and no further changes are suggested.
Discussion
There is a strong correlation between the presented data and the findings that are detailed in the discussion section. The relevance of the findings is high. Identifying a simple, cost-effective prognostic biomarker like PLR, and its trajectory has direct implications for risk stratification and patient management in septic AKI. No changes are suggested in the revised version.
Conclusion
The revised conclusion now correctly distinguishes the strong, validated association of baseline PLR from the suggestive but underpowered finding for ΔPLR in the external cohort. No further changes are suggested.
Dear Authors, thank You for your careful revision. I appreciated your changes. No further questions. My compliments.
No comment
No comment
2No comment
Thank you for your Submission. While the study is valuable and well-presented, several important issues still require clarification before the manuscript can be considered further:
1) Clarify AKI definition (include urine output criteria).
2) Specify variables with missing data and proportions; consider multiple imputation or note as limitation.
3) Describe the mediation analysis method and software in detail.
4) Revise the interpretation of ΔPLR — emphasize that validation was inconclusive and underpowered.
5) Expand the Introduction to include discussion and comparison with other inflammation-related ratios such as NLR.
6) Consider incorporating the recent references suggested by Reviewer 2 (PMID: 39931970, 40943179, 40853379, 40915854, 40429405) if relevant. **PeerJ Staff Note:** It is PeerJ policy that additional references suggested during the peer-review process should only be included if the authors agree that they are relevant and useful.
**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
Title & Abstract
The title highlights the key areas of the study, stating the diagnostic test, the patient population, the outcome of the disease process as well as the retrospective study design. However, when the authors use the phrase “from the U.S. and China”, it gives an impression that there are multiple centers in both countries. While actually, it combines the data from two institutions - Beth Israel Deaconess via MIMIC-IV and West China Hospital. The authors may like to modify the title to “Platelet-Lymphocyte Ratio and Its Dynamic Changes Predict Mortality in Septic Acute Kidney Injury Patients: A Retrospective Multi-Center Study Using U.S. Database and Chinese Hospital Data.”
The abstract provides a nice summary of the study’s background, methods, results and conclusions. It highlights the novelty of the study (changes in PLR over time). Although ΔPLR is explained as “PLR at discharge minus PLR at admission” in the main text, this is not found in the abstract and may leave the readers confused. Further, inclusion of the hazard ratios for how low ΔPLR is linked to death will improve the results in the abstract.
Introduction
The introduction adequately describes the AKI prevalence, mortality associated with septic AKI, the pathophysiology and need for prognostic factors. It identifies PLR as a cost-effective marker with potential for application in septic AKI given the lack of data on this topic. The cited papers are relevant. However, the mechanism could be explained better. It is not very clear why the platelets and lymphocytes specifically matter in sepsis (e.g. relation with thrombosis/inflammation, immune suppression, etc.). There are other ratios as well which have been explored and may have a similar basis (e.g. Neutrophil to Lymphocyte ratio – NLR). How is the PLR different from them (or even better)?
Figures & Tables
The tables and figures are clear, legible and free from unnecessary modification.
Material and Methods
The methods are mostly clear. The authors have explained the data sources, inclusion and exclusion criteria, statistical plan and models.
While the authors have defined sepsis using SOFA score, the definition of AKI as per the KDIGO criteria is based on creatinine changes. The urine output KDIGO criteria is not mentioned. It is not clear if the urine output was used in the AKI definition at all and the study relied solely on creatinine.
On lines 147-148, the authors mention that median substitution was used for data imputation in case of missing values. While median imputation is generally discouraged due to lack of accountability for uncertainty, it may sometimes be necessary. Please specify which variables had missing data, and also mention the proportion of missing data for each. Alternatively, the authors could consider more robust methods like multiple imputation in sensitivity analyses. If this can’t be done, it could be mentioned under the limitations.
The model construction part in the methods lacks details. The usual transparent approach is to pre-specify a core set of covariates based on literature search and clinical experience/knowledge for all the adjusted models, regardless of significance on univariate analysis. The authors also did not use proper tense in reporting the models, they have used future tense in lines 164-168.
The authors have nor described the mediation analysis in sufficient detail. What specific method was used? (e.g., The Baron and Kenny approach, structural equation modeling, or a bootstrapping method?). The software or package used in R should be cited (e.g., mediation package). The text states "Direct and indirect effects were quantified" – please specify the metric used.
Results
The finding that high baseline PLR is a predictor of mortality is consistently demonstrated across different cohorts. The description of ΔPLR is a novel and valuable addition, suggesting that the trajectory of this biomarker can provide critical information about the prognosis and has a greater role beyond a single measurement.
The baseline characteristics show significant differences between the US and Chinese cohorts (e.g., BMI, prevalence of pneumonia, CKD). Although this highlights the importance of external validation, it has not been adequately discussed in either results or discussion to highlight the generalizability of the findings.
Discussion
Overall, there is a strong correlation between the results and the discussion. It compares the results with previous research on PLR under different circumstances and interprets them in light of the suggested biological mechanisms (immune dysregulation).
Line 307, Page 21: Strengthening the phrase "although this finding was not confirmed in the external validation cohort" is necessary. It should clearly state that the external validation for ΔPLR was inconclusive and underpowered, and that larger future studies are needed to confirm this finding. For a fair interpretation, this is a crucial point.
Conclusion
The data for the baseline PLR supports the conclusions. Given the absence of external cohort validation, the ΔPLR claim is excessively strong.
To reflect the different strength of the evidence for baseline PLR versus ΔPLR, the first line of the conclusion should be rephrased.
The manuscript is interesting and focused on a challenging topic, that is the research of new and cheaper indexes.
Introduction is too short and needs to be enlarged by describing the new indexes of inflammtion. At this regard, I suggest to evaluate also Neutrophil/Lymphocyte ratio that is a more stable and reliable index. Making a comparison between these indexes could empower the paper.
I think that PLR alone is not sufficiently strong for its fluctuations in sepsis.
In kidney diseases, reading new manuscripts clud be useful. I suggest:
PMID: 39931970
PMID: 40943179
PMID: 40853379
PMID: 40915854
PMID: 40429405
**PeerJ Staff Note:** It is PeerJ policy that additional references suggested during the peer-review process should only be included if the authors are in agreement that they are relevant and useful.
Please, read the former section. No further questions
No odds.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.