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Peer-Review Record

Is Previous eGFR a Reliable Risk Factor for COVID-19 Death? Single Centre Analysis in Chronic Kidney Disease Patients in Northern Italy

BioMed 2022, 2(1), 82-87; https://doi.org/10.3390/biomed2010008
by Francesca Martino 1,*, Giulia Fanton 2, Fiammetta Zanetti 2, Michela Pascarella 3 and Giacomo Novara 4
Reviewer 1: Anonymous
Reviewer 2: Anonymous
BioMed 2022, 2(1), 82-87; https://doi.org/10.3390/biomed2010008
Submission received: 10 January 2022 / Revised: 30 January 2022 / Accepted: 3 February 2022 / Published: 8 February 2022

Round 1

Reviewer 1 Report

An identification of risk factors of death in CKD patients contracting COVID-19 has significant clinical implications, as the number of COVID-19 positive cases soaring with the new Omicron variant posing unprecedent pressure on the healthcare system. The authors conducted a single-center analysis on a cohort of CKD patients diagnosed with COVID-19, aimed to investigate the predicative value of kidney-function related risk factors on death.  They found that age and basal eGFR were reliable predictors of death among CKD patients with COVID-19.

Major Comments

  1. The finding that eGFR has high prognostic values for CKD patients contracted with COVID-19 may have its clinical meanings, yet the novelty of this study is greatly diminished because the same finding has been reported by Carlson et al. using a much larger cohort of CKD patients with normal controls.
  2. Despite the statistical significance of eGFR and age in predicting COVID-19-related death of CKD patients, their OR values are both close to 1 meaning a positive prognostic rate of 50%. The practical value of such low ORs is questionable.
  3. The insignificance of cardiovascular diseases and diabetes mellitus contradicts with previous studies. In fact, the univariable analysis showed a trend of significance. Could the findings on these two variables caused by a small sample size?

Minor Comments

  1. An explanation of OR is recommended for readers unfamiliar with this metric in logistic regression.
  2. eGFR is typically expressed with a unit of ml/min/1.73m2, not ml/min.
  3. Line 67. The statement “we randomly selected 30 patients” is confusing. Readers may interpret this as the total number of patients involved in this study. Please clarify.

Author Response

Dear Editor,

We would thank you and the reviewer for your assistance. We are glad to resubmit a new version of our job “Is the previous eGFR a reliable risk factor for COVID-19 death?  Single centre analysis in chronic kidney disease patients in northern Italy.”

With regard to the comments of reviewer #1, first of all we want to thank the reviewer for the general positive tone of his/her comments, which permit us to revise our work.

We did our best to improve our manuscript, following his/her suggestions. We hope you can appreciate an advancement.

Specifically,

  1. The finding that eGFR has high prognostic values for CKD patients contracted with COVID-19 may have its clinical meanings, yet the novelty of this study is greatly diminished because the same finding has been reported by Carlson et al. using a much larger cohort of CKD patients with normal controls.”

We think our study moves in the same direction and corroborates Carlson's study, but there are some significant differences:

  1. Carlson did not consider the eGFR value, but he stratified the eGFR for different class of eGFR (>90ml/min, 61-90 ml/min, 60-46 ml/min, 31-45 ml/min, < 30 ml/min). Conversely, we considered the real eGFR (ml/min) in a continuous fashion.
  2. Carlson considered eGFR until seven days before the SARS CoV-2 infection, which could mean SARS CoV-2 infection during the asymptomatic phase of COVID-19 between 5-7 days could influence baseline eGFR. Conversely, we considered the baseline eGFR from the first to 6th months before the infection, so no infection interference should impact the eGFR value. We added a comment in the description of Methods (see page 3 at lines 81-82).

According to your observation, we emphasized the difference between Carlson and our study in the discussion.

  1. “Despite the statistical significance of eGFR and age in predicting COVID-19-related death of CKD patients, their OR values are both close to 1 meaning a positive prognostic rate of 50%. The practical value of such low ORs is questionable.”

As reported in the previous paragraph, our study considered eGFR value, in this scenario OR 0.96 means 4% lower odds of death by a one-unit increase in eGFR, i.e. every 1 ml/min eGFR increase reduces by 4% the probability of death, which is a significant reduction of clinical risk. For example, we have two subjects with 30 ml/min and 42 ml/min of baseline eGFR, respectively. The second subject has a 48% higher probability of survival after SARS CoV-2 infection.

  1. The insignificance of cardiovascular diseases and diabetes mellitus contradicts with previous studies. In fact, the univariable analysis showed a trend of significance. Could the findings on these two variables caused by a small sample size?

 Certainly, the sample size could impact diabetes and cardiovascular disease weight in death risk assessment in chronic kidney disease (CKD) patients, but our primary aim was to see the influence of eGFR on death-related toCOVID-19. Furthermore, diabetes and cardiovascular disease lost their meaning as risk factors in our multivariable analysis, which could suggest a different behaviour of diabetes and cardiovascular disease in death risk assessment in CKD patients. In agreement with your comment, we emphasised in the discussion this is a hypothesis, and future studies are needed to explore this statement.

  1. An explanation of OR is recommended for readers unfamiliar with this metric in logistic regression.”. We add a little comment in the “Discussion” section.
  2. eGFR is typically expressed with a unit of ml/min/1.73m2, not ml/min.”. We changed the text as requested.
  3. Line 67. The statement “we randomly selected 30 patients” is confusing. Readers may interpret this as the total number of patients involved in this study. Please clarify.”. We changed the statement as follows: “Considering the possible covariates for multivariable analysis, we decided to enrol 150 patients (30 patients as reference group without kidney damage and 30 for each stage: IIIa, IIIb, IV, V).”

We hope our efforts to improve the paper will be appreciated by both the editorial team and the reviewers. We hope that the paper could be considered suitable for publication in the present form but we are clearly available to provide further improvements, if required.

Thanks again to invite us to contribute to the special issue about COVID-19.

Sincerely yours,

Francesca Martino

 

Reviewer 2 Report

This study presents us with relevant information on the risk factors related to COVID-19, which makes it very valuable to be taken into account by researchers when formulating solutions to face the pandemic. For this reason, I believe this work should be considered for publication.

Author Response

Dear Editor,

We would thank you and the reviewer for your assistance. We are glad to resubmit a new version of our job “Is the previous eGFR a reliable risk factor for COVID-19 death?  Single centre analysis in chronic kidney disease patients in northern Italy.”

With regard to the comments of reviewer #2, first of all we want to thank the reviewer for the general positive tone of his/her comments. The comments were much appreciated.

 

We hope our efforts to improve the paper will be appreciated by both the editorial team and the reviewers. We hope that the paper could be considered suitable for publication in the present form but we are clearly available to provide further improvements, if required.

Thanks again to invite us to contribute to the special issue about COVID-19.

Sincerely yours,

Francesca Martino

Round 2

Reviewer 1 Report

Thanks to the authors' efforts, all comments have been appropriately addressed. This paper is ready for publication. 

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