Factors associated with contrast-associated acute kidney injury in an emergency department: A cohort study in Lebanon

Moustafa Al Hariri; Sally Al Hassan; Malak Khalifeh; Hani Tamim; Imad El Majzoub; Tharwat El Zahran

doi:10.1371/journal.pone.0316604

Peer Review History

Original SubmissionMay 3, 2024
3 May 2024 Author Response https://doi.org/10.1371/journal.pone.0316604.r001
18 Jul 2024 Decision Letter - Ogochukwu Okoye, Editor PONE-D-24-16070Factors Associated with Contrast-Induced Acute Kidney Injury in a Tertiary Care Center Emergency Department: an Observational Cohort Study.PLOS ONE Dear Dr. El Zahran, 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 term contrast-associated AKI (CA-AKI) is more appropriate and should be used throughout the report. The logistic regression tables should be presented in one table. Clearly state in your statistical plan 1) how predictor variables were selected for the logistic regression analysis 2) How were the confounding variables identified?. Although it is important to include medications and clinical parameters as predictor variables, the authors should check for multicollinearity and address them as appropriate. For any two variables with r > 0.8, only one should be included in the table. In addition, address all concerns raised by both reviewers. Please submit your revised manuscript by Sep 01 2024 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. 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). You should upload this letter as a separate file labeled 'Response to Reviewers'. 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If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. [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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: 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: No Reviewer #2: No ****** 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 ****** 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: Overview: The authors present the results from a single center, retrospective study of 1,832 emergency department patients who underwent CT with contrast between November 2018 and December 2019. They report a prevalence of contrast-induced acute kidney injury (CI-AKI) of 10.9%, and found that BP≥140mmHg, RR≥22, existing history of CKD, and use of several medications (loop diuretics, beta-lactams, allopurinol) were associated with CI-AKI in a logistic regression analysis. Major Comments Overall: - One major issue that must be addressed is that the authors do not differentiate between contrast-associated AKI (CA-AKI) and CI-AKI. CA-AKI, implies a correlative diagnosis of AKI, whereas CI-AKI implies a causative diagnosis. In 2020, the American College of Radiology and the National Kidney Foundation released joint guidelines, published simultaneously in Radiology and Kidney Med (Davenport et al., 2020) that distinguishes between the two. This study must be cited in this paper. The authors methodologic approach does not provide a control group for analysis, therefore no causative link can be drawn between the AKI these patients developed and the contrast they received. Thus, it is crucial that “CI-AKI” be replaced by “CA-AKI” throughout the manuscript. Additionally, this difference should be briefly discussed in the introduction and the discussion, as it helps interpret the authors’ findings. Abstract: - Replace “CI-AKI” with “CA-AKI” throughout abstract - In the conclusions section, you mention “age” as a factor to consider, but this was not significantly associated with CA-AKI in your model. Please remove. Introduction: - Please provide citations throughout for each sentence that cites data or concepts from other studies Methods: - The study aim should be moved to the last sentence of the introduction - It is unclear what variables you adjusted for in your logistic regression model: please clarify which variables either in the methods, or in table 2 where you report regression outputs Results: - For Table 2, is this a multiple logistic regression model or are these bivariate p values? If it was a multiple logistic regression model, it would be helpful to show the bivariate analysis to see how ORs changed after being included in the multivariate model - For table 2, it would be helpful to know the row percentages: For example: how many patients with qSOFA 0, 1 or 2 had AKI? How many patients on loop diuretics had AKI compared to those not on loop diuretics? These are the proportions that matter so we can understand how prevalence of AKI differs by each characteristic Discussion: - It is interesting that BP and RR are associated with CA-AKI; but how do you suggest interpreting this? It is very likely that elevated BP is simply a marker of undiagnosed hypertension, which itself is predictive of AKI during any admission (Jiang 2021, BMC Nephrology). Similarly, elevated RR may be a marker of acuity of illness; this elevated acuity of illness likely predisposes an increased propensity to AKI regardless of contrast administration. For example, conditions such as volume overload and sepsis would increase the RR and both are known to contribute to AKI. Indeed, it was unsurprising that AKI was more common in the qSOFA 1 group. These diagnoses also increase the likelihood that someone might get a contrast study to evaluate for infection or pulmonary embolism, for example. This must be discussed. - Must add lack of control group to the limitations part of discussion Reviewer #2: We would like to thanks to the authors for giving me the opportunity to review the manuscript entitled "Factors Associated with Contrast-Induced Acute Kidney Injury in a Tertiary Care Center Emergency Department: an Observational Cohort Study". The manuscript is very interesting, but needs a few changes to improve it. Introduction Why have the authors placed the objective of the study in the method section? We believe that the objective of the study should be placed at the end of the context. Method This study was approved by the IRB, Authors should explain the abbreviation at the first appearance in the text. Study approval may be presented in a different section as an Ethics Statement. The authors must correctly state the inclusion criteria: did the authors include all patients? What is the age criterion for inclusion? The authors report that patients receive a mean contrast dose of 2ml/kg. As this is an average, could the authors add the standard deviation? The author should specify the type of iodinated contrast medium used: iso or low-osmolarity? In the methods section Outcome measures: this title would normally correspond to data collection. home medication, vitals, ED management (medications and IV administration), home medications, In this sentence, home medication is repeated laboratory workup The authors should specify which laboratory data were collected and reported in Table 1, where the general characteristics of the study are presented according to AKI status. Could the authors provide information on the stage of AKI and incidence of hemodialysis in these AKI-IC cases? Definition of AKI as an increase in creatinine of 0.3 mg/dl (26 mmol/l) within 48 hours: please correct the unit to 26 µmol/L The title definition of AKI should be replaced by an operational definition in which the authors could report the definition of Aki and add the definition of CKD. Statistical analysis Continuous variables were presented using mean and standard deviation (mean ± SD). The authors can confirm that all data were normally distributed, as they did not present the results as median (IQR). Results In Table 1, what is the difference between antiviral and antiretroviral drugs? In Table 1, the authors should compare baseline creatinine values between the AKI and non-AKI groups. Patients who received lithium (30.5% vs. 22%, p=0.008): these results do not correspond to those reported in Table 1. Patients with high blood pressure (≥140 mmHg): this result is not consistent with that reported in Table 3. Why were many factors significant in the univariate logistic regression not presented in Table 3 in the multivariate logistic regression? Please write ˂ 0.001 for the p-value of 0.000. Limitation Please correct the KDIGO definition of acute renal failure. For KDIGO Translated with www.DeepL.com/Translator (free version) ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). 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Revision 1
25 Aug 2024 Author Response Dr. Ogochukwu Chinedum Okoye Academic Editor PLoS One August 25, 2024 Dear Dr. Ogochukwu Chinedum Okoye, On behalf of the authors of our submitted manuscript “Contrast-Associated Acute Kidney Injury: an Observational, Cohort Study in an Emergency Department of a Tertiary Care Center” with submission ID PONE-D-24-11651, I would like to thank you and the reviewers for the time to review and suggest improvements for our manuscript. I am submitting herein the point-by-point response addressing the comments and suggestions of the editor(s) and the reviewers. Dear Dr. El Zahran, 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 term contrast-associated AKI (CA-AKI) is more appropriate and should be used throughout the report. The logistic regression tables should be presented in one table. Clearly state in your statistical plan 1) how predictor variables were selected for the logistic regression analysis 2) How were the confounding variables identified?. Although it is important to include medications and clinical parameters as predictor variables, the authors should check for multicollinearity and address them as appropriate. For any two variables with r > 0.8, only one should be included in the table. In addition, address all concerns raised by both reviewers. Response: We thank the reviewer for summarizing the reviewers’ points. We have amended the use of contrast induced AKI into Contrast Associated AKI (CA-AKI) on multiple occasions in the manuscript. Logistic regression analysis is presented in table 3 of the manuscript. We have reported the As for the variables that were selected to be tested in the logistic models, we have amended our method section to clarify the selection process and we added to the footnote of Table 3 the variables that were accounted for upon generating the logistic regression model. As for the collinearity of the variables included in the logistic regression model, we have performed Variance Inflation Factor (VIF) values. In the below table, we present the VIF values of the variables, which were all below 5, indicating a low collinearity between the variables. Variable VIF value Age (≥ 60 years) 1.086826 SBP (≥ 140) 1.053905 RR (≥ 22) 1.067888 Chronic Kidney Disease 1.020159 Loop Diuretic 1.142967 Beta-Lactams 1.120602 Allopurinol 1.018106 Vancomycin 1.130351 3. In the online submission form, you indicated that "The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request." All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Response: We thank the editor and the reviewers for this suggestion. We have deposited our dataset in Qatar University data repository, which is accessible through the following link: https://qspace.qu.edu.qa/handle/10576/57874 The data sharing statement in the manuscript was amended accordingly. 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: Partly Reviewer #2: Yes ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: 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: No Reviewer #2: No ________________________________________ 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 ________________________________________ 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: Overview: The authors present the results from a single center, retrospective study of 1,832 emergency department patients who underwent CT with contrast between November 2018 and December 2019. They report a prevalence of contrast-induced acute kidney injury (CI-AKI) of 10.9%, and found that BP≥140mmHg, RR≥22, existing history of CKD, and use of several medications (loop diuretics, beta-lactams, allopurinol) were associated with CI-AKI in a logistic regression analysis. Major Comments Overall: - One major issue that must be addressed is that the authors do not differentiate between contrast-associated AKI (CA-AKI) and CI-AKI. CA-AKI, implies a correlative diagnosis of AKI, whereas CI-AKI implies a causative diagnosis. In 2020, the American College of Radiology and the National Kidney Foundation released joint guidelines, published simultaneously in Radiology and Kidney Med (Davenport et al., 2020) that distinguishes between the two. This study must be cited in this paper. The authors methodologic approach does not provide a control group for analysis, therefore no causative link can be drawn between the AKI these patients developed and the contrast they received. Thus, it is crucial that “CI-AKI” be replaced by “CA-AKI” throughout the manuscript. Additionally, this difference should be briefly discussed in the introduction and the discussion, as it helps interpret the authors’ findings. Response: We appreciate the reviewer’s insightful comment. We have addressed this issue by making the following changes to the manuscript: We have replaced "CI-AKI" with "CA-AKI" throughout the manuscript to reflect the appropriate terminology as per the guidelines from the American College of Radiology and the National Kidney Foundation (Davenport et al., 2020). We have added the following statement to the Background section to differentiate between CA-AKI and CI-AKI: " In 2020, the American College of Radiology and the National Kidney Foundation released joint guidelines distinguishing between CA-AKI and contrast-induced acute kidney injury (CI-AKI). CA-AKI refers to AKI that occurs in temporal association with contrast media administration but does not imply causation, whereas CI-AKI implies a direct causal relationship between contrast media and AKI (Davenport et al., 2020)." We have also added the following sentences at the end of the Introduction section to briefly discuss the difference between CA-AKI and CI-AKI: "It is important to differentiate between CA-AKI and CI-AKI. CA-AKI is a correlative diagnosis indicating that AKI occurred after contrast administration, while CI-AKI implies a causative diagnosis. This distinction is crucial as our study design does not allow for a causal inference. Therefore, we will use the term CA-AKI in this manuscript (Davenport et al., 2020)." We have added the following paragraph to the Discussion section to further elaborate on the difference between CA-AKI and CI-AKI and its relevance to our findings: "Our study identified several factors associated with the development of CA-AKI in patients receiving contrast media. It is essential to note that CA-AKI refers to AKI occurring in temporal association with contrast media administration without implying causation, whereas CI-AKI suggests a direct causal relationship. Given the retrospective design of our study and the absence of a control group, we cannot establish a causative link between contrast media and AKI. This aligns with the guidelines from the American College of Radiology and the National Kidney Foundation, which recommend using the term CA-AKI to avoid overstating the risk of contrast media (Davenport et al., 2023, Abbasi et al., 2022, & Weinreb et al. 2021)." References: • Davenport, M. S., et al. (2020). Use of Intravenous Iodinated Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation. Radiology and Kidney Medicine. • Davenport MS, Perazella MA, Nallamothu BK. Contrast-Induced Acute Kidney Injury and Cardiovascular Imaging: Danger or Distraction? Circulation. 2023;147(11):847-9. doi: doi:10.1161/CIRCULATIONAHA.122.062783. • Abbasi N, Glazer DI, Saini S, Sharma A, Khorasani R. Utility of Patient-Reported Risk Factors for Identifying Advanced Chronic Kidney Disease Before Outpatient CT: Comparison With Recent ACR/NKF Consensus Criteria. American Journal of Roentgenology. 2022;219(3):462-70. doi: 10.2214/ajr.22.27494. PubMed PMID: 35383485. • Weinreb JC, Rodby RA, Yee J, Wang CL, Fine D, McDonald RJ, et al. Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation. Radiology. 2021;298(1):28-35. doi: 10.1148/radiol.2020202903. PubMed PMID: 33170103. Abstract: - Replace “CI-AKI” with “CA-AKI” throughout abstract Response: We thank the reviewer for this suggestion. We replaced CI-AKI throughout the manuscript with CA-AKI. - In the conclusions section, you mention “age” as a factor to consider, but this was not significantly associated with CA-AKI in your model. Please remove. Response: We thank the reviewer for this suggestion. However, we respectfully disagree. Our logistic regression model, presented in Table 3, indicates that age (specifically, being 60 years or older) is significantly associated with a higher likelihood of developing CA-AKI. The adjusted odds ratio (aOR) for age being 60 years or older is 1.547, with a 95% confidence interval of 1.091 to 2.195 and a p-value of 0.014. Therefore, age should be included in the conclusions as a factor associated with CA-AKI. Introduction: - Please provide citations throughout for each sentence that cites data or concepts from other studies Response: We thank the reviewer for this suggestion. We added citation indications for the data and concepts included in the background section. The added citations are: 3. Andreucci M. Iodinated Contrast-Induced Acute Kidney Injury. Pathophysiology and Prevention. Giornale di Tecniche Nefrologiche e Dialitiche. 2017;29(1):11-9. doi: 10.5301/gtnd.2017.16584. 4. Ye J, Liu C, Deng Z, Zhu Y, Zhang S. Risk factors associated with contrast-associated acute kidney injury in ST-segment elevation myocardial infarction patients: a systematic review and meta-analysis. BMJ Open. 2023;13(6):e070561. doi: 10.1136/bmjopen-2022-070561. 5. Pistolesi V, Regolisti G, Morabito S, Gandolfini I, Corrado S, Piotti G, et al. Contrast medium induced acute kidney injury: a narrative review. Journal of Nephrology. 2018;31(6):797-812. doi: 10.1007/s40620-018-0498-y. 7. Maioli M, Toso A, Leoncini M, Musilli N, Grippo G, Ronco C, et al. Bioimpedance-Guided Hydration for the Prevention of Contrast-Induced Kidney Injury: The HYDRA Study. Journal of the American College of Cardiology. 2018;71(25):2880-9. doi: https://doi.org/10.1016/j.jacc.2018.04.022. Methods: - The study aim should be moved to the last sentence of the introduction Response: We thank the reviewer for the suggestion. We amended the manuscript write-up according to the suggestion. - It is unclear what variables you adjusted for in your logistic regression model: please clarify which variables either in the methods, or in table 2 where you report regression outputs Response: we thank the reviewer for this question. We have clarified the variables adjusted for in our logistic regression model as follows: We have presented the bivariate analysis (chi-square or independent t-test) of our variables in Tables 1 and 2. We also added the False Discovery Rate (FDR) value of the results to account for multiple comparisons. We assessed and presented the unadjusted odds ratio (OR) of each variable to assist in selecting the variables for the logistic regression model. We relied on the unadjusted OR confidence interval rather than just the p-value or q-value from the bivariate analysis. The results of the logistic regression are presented in Table 3. The variables selected for the logistic regression model are listed as a footnote underneath Table 3. The Methods section describing the selection of variables for the logistic regression reads as follows: “Logistic regression was then done to adjust confounding variables and test the association between CA-AKI and other variables. Variables that showed a significant confidence interval of the unadjusted OR and clinically relevant were selected to build the logistic regression model.” Results: - For Table 2, is this a multiple logistic regression model or are these bivariate p values? If it was a multiple logistic regression model, it would be helpful to show the bivariate analysis to see how ORs changed after being included in the multivariate model Response: We thank the reviewer for this important question. Table 2 presents the bivariate p-values from our analysis and not multiple logistic regression models. We added the unadjusted odds ratio (OR) for each of the variables and their 95% confidence intervals (95% CI) to this table to aid in selecting factors for the logistic regression model presented in Table 3. To enhance clarity, we have updated Tables 1 and 2 to clearly indicate that they present bivariate p-values and unadjusted ORs. Additionally, we have included footnotes in Tables 1 and 2 to clarify that the ORs and the 95% CIs presented in these tables are generated from unadjusted logistic regression. The modified footnotes for tables 1 and 2 read as follows: “Data are presented as numbers with percentages. The p-value for the difference between AKI vs. no AKI is calculated by chi-square, Fisher´s exact test, or T-test where appropriate. The q-value is the False Discovery Rate (FDR) significance accounting for multiple comparisons. The unadjusted Odd Ratio (OR) for each variable was calculated without accounting for any other factor. 95% CI is the confidence interval of the OR for each variable.” - For table 2, it would be helpful to know the row percentages: For example: how many patients with qSOFA 0, 1 or 2 had AKI? How many patients on loop diuretics had AKI compared to those not on loop diuretics? These are the proportions that matter so we can understand how prevalence of AKI differs by each chara Attachments Attachment Submitted filename: Point by point response Nephrotox.docx https://doi.org/10.1371/journal.pone.0316604.r003
21 Nov 2024 Decision Letter - Ogochukwu Okoye, Editor PONE-D-24-16070R1Factors Associated with Contrast-Associated Acute Kidney Injury in a Tertiary Care Center Emergency Department: an Observational Cohort Study.PLOS ONE Dear Dr. El Zahran, 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 by reviewer 2. Please submit your revised manuscript within Jan 05 2025 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. 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). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Ogochukwu Chinedum Okoye Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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 #2: (No Response) Reviewer #3: (No Response) ******** 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 #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: 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 #2: Yes Reviewer #3: Yes ****** 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 #2: Yes Reviewer #3: 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 #2: We thank the editor for the opportunity to review the revised manuscript. We feel that the manuscript is improved, but requires some minor change Introduction This study aims to assess the factors associated with the development of CA-AKI in patients who received computed tomography (CT) scans with contrast during their presentation to an academic Emergency Department in a tertiary care center. It is essential to differentiate between CA-AKI and CI-AKI. CA-AKI is a correlative diagnosis indicating that AKI occurred after contrast administration, while CI-AKI implies a causative diagnosis. This distinction is crucial as our study design does not allow for a causal inference. Therefore, we will use the term CAAKI in this manuscript [2]. We believe that the second sentence of this paragraph is repetitive and should be deleted. The authors have already correctly distinguished between CA-AKI and CI-AKI in the second paragraph of their introduction. Methods Study participants received an average of 2ml1ml/Kg for routine CT and 1.5ml/Kg for angio-CT of low-osmolar contrast medium (Omnipaque 350) contrast solution In front of 1ml/kg please delete '2ml Patients’ details were prepared as reports by the EPIC team Please define the term “EPIC” Results Discussion We also think it would be interesting for the authors of this interesting article to comment on the incidence of CA-AKI reported in their study. In the context where the authors report an association between high respiratory rate and CA-AKI, the higher incidence of CA-AKI in COVID-19 patients (26.1%) (mainly respiratory pathology) could be a further argument in favour of the association between high respiratory rate and CA-AKI. Nlandu Y, Makulo JR, Essig M, Sumaili E, Lumaka A, Engole Y, Mboliasa MF, Mokoli V, Tshiswaka T, Nkodila A, Bukabau J, Longo A, Kajingulu F, Zinga C, Nseka N. Factors associated with acute kidney injury (AKI) and mortality in COVID-19 patients in a Sub-Saharan African intensive care unit: a single-center prospective study. Ren Fail. 2023;45(2):2263583. doi: 10.1080/0886022X.2023.2263583. Epub 2023 Oct 23. PMID: 37870858; PMCID: PMC11001370. Limitations On the other hand, the selection bias in our study was reduced by the fact that around 17% of the study participants exhibited an abnormal (above and lower the normal range) baseline creatinine level. Among these 306 participants, only 42 fulfilled the KODIGO definition of AKI. Please correct KODIGO to KDIGO Reviewer #3: The Abstract and introduction were well written and captivating with minor errors as highlighted in the attachment . The aim was clear and succinct Overall methodology was thorough and aligned well with the study aim. However, it may be clearer to structure the paragraph with bullet points or distinct sections for "Study Design", "Setting", Ethical Approval", for better organization. The results with tables and illustrations was well captured and discussion was sound as well. By and large, very fine manuscript. ****** 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 #2: No Reviewer #3: 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.] 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 PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Nephrotox_manuscript_PloS one.docx REVIEW COMMENTS.docx https://doi.org/10.1371/journal.pone.0316604.r004
Revision 2
12 Dec 2024 Author Response We thank the editor and the reviewers for sharing their suggestions to improve our manuscript “Factors Associated with Contrast-Associated Acute Kidney Injury in a Tertiary Care Center Emergency Department: an Observational Cohort Study” with submission number “PONE-D-24-16070R1.” We would like to indicate that the title of the manuscript was modified according to the suggestion on the provided manuscript word document file to the following: “Factors Associated with Contrast-Associated Acute Kidney Injury in an Emergency Department: A Cohort Study in Lebanon.” We have reviewed all the comments added to the document and implemented the needed changes. All changes were tracked on the file. Additionally, please find below our point-by-point response to the points raised by the reviewers. Reviewers' comments the Author: Reviewer #2: We thank the editor for the opportunity to review the revised manuscript. We feel that the manuscript is improved, but requires some minor change Introduction This study aims to assess the factors associated with the development of CA-AKI in patients who received computed tomography (CT) scans with contrast during their presentation to an academic Emergency Department in a tertiary care center. It is essential to differentiate between CA-AKI and CI-AKI. CA-AKI is a correlative diagnosis indicating that AKI occurred after contrast administration, while CI-AKI implies a causative diagnosis. This distinction is crucial as our study design does not allow for a causal inference. Therefore, we will use the term CAAKI in this manuscript [2]. We believe that the second sentence of this paragraph is repetitive and should be deleted. The authors have already correctly distinguished between CA-AKI and CI-AKI in the second paragraph of their introduction. Response: We thank the reviewer for the suggestion. We removed the repetitive statement. Methods Study participants received an average of 2ml1ml/Kg for routine CT and 1.5ml/Kg for angio-CT of low-osmolar contrast medium (Omnipaque 350) contrast solution In front of 1ml/kg please delete '2ml Response: We thank the reviewer for the suggestion. The edits are implemented in the method section. Patients’ details were prepared as reports by the EPIC team Please define the term “EPIC” Response: We thank the reviewer for the suggestion. EPIC is the name of the Electronic Health record used in our institution. Therefore, it is defined as such is the method section “Electronic Health Record (EPIC) team .” Results Discussion We also think it would be interesting for the authors of this interesting article to comment on the incidence of CA-AKI reported in their study. In the context where the authors report an association between high respiratory rate and CA-AKI, the higher incidence of CA-AKI in COVID-19 patients (26.1%) (mainly respiratory pathology) could be a further argument in favour of the association between high respiratory rate and CA-AKI. Nlandu Y, Makulo JR, Essig M, Sumaili E, Lumaka A, Engole Y, Mboliasa MF, Mokoli V, Tshiswaka T, Nkodila A, Bukabau J, Longo A, Kajingulu F, Zinga C, Nseka N. Factors associated with acute kidney injury (AKI) and mortality in COVID-19 patients in a Sub-Saharan African intensive care unit: a single-center prospective study. Ren Fail. 2023;45(2):2263583. doi: 10.1080/0886022X.2023.2263583. Epub 2023 Oct 23. PMID: 37870858; PMCID: PMC11001370. Response: We thank the reviewer for the suggestion. We would like to emphasize that the study was conducted before the COVID period, and no COVID-19 patients were included in the study. Therefore, we will not compare our results to the ones reported in the proposed study. Limitations On the other hand, the selection bias in our study was reduced by the fact that around 17% of the study participants exhibited an abnormal (above and lower the normal range) baseline creatinine level. Among these 306 participants, only 42 fulfilled the KODIGO definition of AKI. Please correct KODIGO to KDIGO Response: We thank the reviewer for the suggestion. We corrected this typing mistake. Reviewer #3: The Abstract and introduction were well written and captivating with minor errors as highlighted in the attachment . The aim was clear and succinct Overall methodology was thorough and aligned well with the study aim. However, it may be clearer to structure the paragraph with bullet points or distinct sections for "Study Design", "Setting", Ethical Approval", for better organization. The results with tables and illustrations was well captured and discussion was sound as well. By and large, very fine manuscript. Response: We thank the reviewer for the revision. Attachments Attachment Submitted filename: Reviewer responses-2.docx https://doi.org/10.1371/journal.pone.0316604.r005
15 Dec 2024 Decision Letter - Ogochukwu Okoye, Editor Factors Associated with Contrast-Associated Acute Kidney Injury in an Emergency Department: A Cohort Study in Lebanon PONE-D-24-16070R2 Dear Dr. El Zahran, 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. If you have any questions relating to publication charges, 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 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, Ogochukwu Chinedum Okoye Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0316604.r006
Formally Accepted
Acceptance Letter - Ogochukwu Okoye, Editor PONE-D-24-16070R2 PLOS ONE Dear Dr. El Zahran, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. 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. Ogochukwu Chinedum Okoye Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0316604.r007

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