PONE-D-20-24607

Monitoring Peripheral Perfusion in Sepsis associated Acute Kidney Injury: Analysis of Clinical Outcomes

PLOS ONE

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PLOS ONE

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: I Don't Know

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The study addressed an interesting clinical question. However, there are some issues need to be addressed.

1. "To the best of our knowledge, this is the first study to comprehensively and accurately address the importance of monitoring peripheral perfusion in Sepsis associated AKI (SA-AKI)."---this statement is not true because peripheral perfusion has been extensively explored. I suggest to rephrase this sentence to a more focused area with novelty.

2. This is a cohort study, not a case-control study; so you need to explicitly declared this.

3. The time window for the PI and CRT measurement should be explicitly declared; and its relatioship to the AKI assessment should also be clarified. This is important for the causal inference.

4. details of the Linear Model Mixed Effects test should be clarified. For example, did you allow slope to differ between individials? or random-effects were just allowed for the intercept term? How did you specify random-effects and fixed effect terms?

5. when you identify independent predictors for AKI, you must clarify the temporal relationship between outcome and predictors. The outcome (AKI) may be present on ICU admission.

6. When you explore the association of fluid balance and PI/CRT, you need to clarify the temporal relationship in the METHOD section.

Reviewer #2: The authors present an interesting manuscript about microcirculation in septic patients with or without acute kidney injury. I have some remarks, split per section, below.

Abstract:

- Could the authors shortly mention here that AKI was defined based on KDIGO on both serum creatinine and urine output?

- Numbers at the beginning of a sentence should be fully spelled

- In the last part, it is mentioned that the presence of peripheral hypoperfusion may be an important prognostic marker. Could the authors add here for what specific outcome this prognostic value is?

Introduction:

- Could the authors elaborate either here or in the discussion about how the ´´phase of sepsis´´ may influence the made measurements? I.e. at certain points patients may have high cardiac index with even shortened CRT before suffering from peripheral hypoperfusion and a prolonged CRT.

- On page 4, there are the numbers 1 and 3 in superscript. Should these be references? Please clarify

- In the last section of the introduction (and in the title), the authors mention clinical outcomes, where later the most focus is on mortality. Could this be specified or changed?

Methods:

- One of the exclusion criteria is inaccessible peripheral perfusion, could the authors provide an example?

- How were missing values handled? I.e. missing urine output data or missing pre-admission creatinine? Was a baseline eGFR assumed?

- The CRT was measured at what place? Index finger? This is important for the reference value.

- How did the authors decide on the limit of 3 secs for the CRT to be abnormal? In the stated reference, 2.4 s is mentioned for septic shock pts and 5 for critically ill, previous papers have stated 4.5 seconds.

- The outcome section of the methods more clearly describes the objective, suggest to write something similar in the last paragraph of the introduction.

- I cannot follow the rationale behind the sample size calculation and the aimed OR of 7.0 between groups, could the authors elaborate?

Results:

- What was the time between admission, study inclusion and fluid resuscitation?

- The authors could consider to either shorten or move table 1 and 2 to the appendices. They are informative but do not provide main answers to the main objectives of the study.

- Did the authors also consider using CRT as a continuous variable?

- Could the authors provide more data on the received fluid resuscitation?

- In figure 4, the difference between PI and changes over time is plotted, splitted for survivors and non-survivors. The title of the figure states the prognostic significance, and a p value. I do not fully comprehend: does this mean that the changes were prognostic (as there was not a significant alteration) or that all measurements, apart from eachother, were consistently different between survivors and non survivors?

Discussion:

- Could the authors specify and clarify what specific pieces of evidence contribute to the support of the use of? CRT? PI? Both? For AKI? Mortality?

- Please change the word humans into something like ´´caregivers´´

- On page 16, the use of CRT dichotomously or continuously is discussed. Perhaps the authors could add a sensitivity analysis using a different cut off value to see whether this changes the main findings? And here discuss the potential consequences?

- In the conclusion, could the authors clarify the sentence : ´´however, the presence of … independently´´. The sentence reads a bit difficult and it is unclear to me what the specific prognostic marker is for (and for what outcome).

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Reviewer #1: Yes: Zhongheng Zhang

Reviewer #2: No

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Monitoring Peripheral Perfusion in Sepsis associated Acute Kidney Injury: Analysis of Mortality

PONE-D-20-24607R1

Dear Dr. de Miranda,

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.

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Kind regards,

Corstiaan den Uil

Academic Editor

PLOS ONE

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