Effects of Zinc Acetate Hydrate Supplementation on Renal Anemia with Hypozincemia in Hemodialysis Patients

Round 1

Reviewer 1 Report

Authors supplemented to oral zinc to HD patients with hypozincemia and  found that they can improved the ESA resistance. The study is direct and well performed. Comments are as follows.

1. One major mistake is t he unit of zinc levels described in the abstract, but not in other sections. Please correct them.

2. Authors described that this is a "retrospective" study. For this study, authors will have to examine the zinc levels in HD patients, and supplement oral zinc to those with hypozincemia, and follow their parameters to have the conclusion. How can this study be retrospective?   I imagine: The only possibility to have a retrospective study is that zinc supplement was actually given every HD patients and you went back to analyze patient subgroups. AND, you found that zinc supplement can improved ERI in patients with hypozincemia.   Please let readers know how it really is.

Author Response

Comments from Referee

Comment :

Authors supplemented to oral zinc to HD patients with hypozincemia and  found that they can improved the ESA resistance. The study is direct and well performed. Comments are as follows.

1. One major mistake is the unit of zinc levels described in the abstract, but not in other sections. Please correct them.
2. Authors described that this is a "retrospective" study. For this study, authors will have to examine the zinc levels in HD patients, and supplement oral zinc to those with hypozincemia, and follow their parameters to have the conclusion. How can this study be retrospective?   I imagine: The only possibility to have a retrospective study is that zinc supplement was actually given every HD patients and you went back to analyze patient subgroups. AND, you found that zinc supplement can improved ERI in patients with hypozincemia.   Please let readers know how it really is.

Response:

We would like to thank the reviewer for his/her appraisal of our manuscript.

We agree with the comment.

1. In the abstract, we have changed the units for zinc (lines 19–20).
2. In the introduction, we have changed the retrospective study to a case series study (line 60).

 

 

Author Response File: Author Response.pdf

Reviewer 2 Report

To the authors

 

Thank you for the opportunity to review this article.

 

In this study, the authors investigated whether zinc supplementation with zinc acetate hydrate improved renal anemia with hypozincemia in patients undergoing hemodialysis. This report is very interesting. However, previous randomized controlled study has already shown that zinc supplement reduces ESA doses and ERI in hemodialysis patients with hypozincemia (PMID: 25988769). What is the novelty of this study? About the material and methods section, are the variables normally distributed? This study is small; thus, variables are probably distributed non-normally. If variables are distributed non-normally, the T-test is inappropriate. Furthermore, this study has no description of ethical approval and IRB number. Is this study approved by the ethics committee? This study has many concerns in addition to what is described above, and I suggest the authors reconsider the novelty, ethical considerations, and study design.

Author Response

Comments from Referee

Comment :

 

We would like to thank the reviewer for his/her appraisal of our manuscript.

We have added the Institutional Review Board Statement at the end of the text (after line 208).

It was highlighted by you that the Wilcoxon signed rank sum test was used in this study for the statistical examination method, considering that the T-test was inappropriate. In this paper, we have used the Wilcoxon signed rank sum test to examine the data. Hence, we have changed the description in the text (lines 205–206).

Regarding the novelty of this paper, as you pointed out, a similar report has already been made. However, we are considering the following two points regarding this paper:

First, we have used MCH to evaluate the effect of correcting hypozincemia with zinc supplementation on renal anemia. Regarding the evaluation of anemia by MCH, iron supplementation is recognized. However, based on our investigation, zinc supplementation has not been reported yet. This time, we believe that we were able to show that better-quality hematopoiesis can be performed using easily measurable MCH from the viewpoint of zinc supplementation.

The other is that zinc acetate hydrate is a zinc preparation with higher zinc content. Thus, it has become possible to provide appropriate zinc supplementation to more hypozincemic patients. This study was impactful because we were able to consider the merits and demerits of zinc hydrate preparations.

Author Response File: Author Response.pdf

Reviewer 3 Report

This manuscript contains clinically important data which support that administration of zinc acetate hydrate has a beneficial effect in patients with renal anemia undergoing hemodialysis. The study was performed on a relatively small sample size. Furthermore, a few points should be clarified before the final publication of the manuscript.

Specific comments:

    1. L36: “ESA-resistant” instead of “ESA-renal”

    2. In the case of Figures 1 and 2, the order of the (sub)figures should follow the logic of the text.

    3. There is a discrepancy between the Abstract (L13) and Materials and Methods (L205) with respect to the applied statistical test. Please, clarify this.

    4. The Ethical permission of the study should be disclosed in the manuscript.

Author Response

Comments from Referee

Comment :

 

This manuscript contains clinically important data which support that administration of zinc acetate hydrate has a beneficial effect in patients with renal anemia undergoing hemodialysis. The study was performed on a relatively small sample size. Furthermore, a few points should be clarified before the final publication of the manuscript.

Specific comments:

1. L36: “ESA-resistant” instead of “ESA-renal”
2. In the case of Figures 1 and 2, the order of the (sub)figures should follow the logic of the text.
3. There is a discrepancy between the Abstract (L13) and Materials and Methods (L205) with respect to the applied statistical test. Please, clarify this.
4. The Ethical permission of the study should be disclosed in the manuscript.

Response :

We would like to thank the reviewer for his/her appraisal of our manuscript.

We agree with the comment.

 

1. In the introduction, we have changed ESA-renal to ESA-resistant (line 36).
2. We have changed the order of Figures 1 and 2 (lines 73 and 78) and added Figures 1 and 2 according to the content of the text (lines 65–71).
3. In this paper, we have used the Wilcoxon signed rank sum test to examine the data. Hence, we have changed the description in the text (lines 205–206).
4. We have added the Institutional Review Board Statement at the end of the text (after line 208).

 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

To the authors,

Thank you for the opportunity to review the revised manuscript and for taking into consideration my suggestions. This study was dramatically improved, and I find the revised version much more suitable for publication.