Cardiovascular Disease and Dialysis: A Review of the Underlying Mechanisms, Methods of Risk Stratification, and Impact of Dialysis Modality Selection on Cardiovascular Outcomes

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study is about cardiovascular disease in dialysis patients. The review is quite good written. Authors describe methods evaluating cardiovascular risk in dialysis patients. Then they describe laboratory changes which might increase cardiovascular risk (ex. anemia, overload). However, there are some lacking data, that should be unederscored:

-       The type of the disease which “provided’ to the ESRD i.e. do autoimmune diseases SLE or vasculitis are associated with higher risk of cardiovascular complications?

-       Author should include more molecular, novel data i.e. the role of cytokines.

-       Authors should write more about comorbidities which may influence on cardiovascular risk.

-       Authors should write how they searched articles.

-       There are lacking data about limitations of the study.

-       The references are in the appropriate, however insufficient.

Author Response

This study is about cardiovascular disease in dialysis patients. The review is quite good written. Authors describe methods evaluating cardiovascular risk in dialysis patients. Then they describe laboratory changes which might increase cardiovascular risk (ex. anemia, overload). However, there are some lacking data, that should be unederscored:

-       The type of the disease which “provided’ to the ESRD i.e. do autoimmune diseases SLE or vasculitis are associated with higher risk of cardiovascular complications?

There is limited data to suggest that having GN as the underlying cause of ESRD does not lead to higher incidence of CVD. A refernce to support this has been added. 

-       Author should include more molecular, novel data i.e. the role of cytokines.

The aim of this review article is to focus on the most current literature surrounding the decision to choose one dialysis modality over another. The discussion regarding underlying risk factors for CVD was merely to provide background rationale as to why, a priori, a continuous home modality might be superior to intermittent hemodialysis when it comes to cardiovascular disease.  

-       Authors should write more about comorbidities that may influence on cardiovascular risk.

Are there specific co-morbid conditions that need to be added to the discussions of hypertension/volume overload, anemia/uremia/chronic inflammation, and vascular calcification? The intent was to highlight unique features to the dialysis population that put them at risk in addition to traditional risk factors like smoking, diabetes, hyperlipidemia, and age.

-       Authors should write how they searched articles.

See the updated methods sectionn

-       There are lacking data about limitations of the study.

This is a review article, not a meta-analysis.

-       The references are in the appropriate, however insufficient.

Additional references added

Reviewer 2 Report

Comments and Suggestions for Authors

1.      For a review, the number of the citations seems low, consider 70-100 citations?

2.      Introduction: “Death from CVD is approximately 20 times higher in dialysis patients than in the general population.” Did that mention timeframe? 1 year? 10 years

3.      You didn't find direct relationship to connect Mineral bone disease to CV disease in dialysis population? If so, This section 4 doesn't seem necessary under the title" CV disease in dialysis patients”

4.      Section 5: I think you need to find reference to support that 1. More percentage of PD patients had exercise than HD patients did 2. Exercise reduce CV mortality or incidents in dialysis patients.

5.      The SGLT2i and Kerendia reduce CV risk in CKD patients non yet in dislaysis, is there any data about their CV effect on dialysis patients?

Comments on the Quality of English Language

nil

Author Response

1. For a review, the number of the citations seems low, consider 70-100 citations?
2. Introduction: “Death from CVD is approximately 20 times higher in dialysis patients than in the general population.” Did that mention timeframe? 1 year? 10 years

When compared to age, gender, race, and diabetes status controls.

3. You didn't find direct relationship to connect Mineral bone disease to CV disease in dialysis population? If so, This section 4 doesn't seem necessary under the title" CV disease in dialysis patients” 

Hyperphosphatemia, elevations in FGF-23, and alterations in klotho transcription and metabolism are all linked to vascular calcification, endothelial dysfunction, hypertension, and increased mortality.

4. Section 5: I think you need to find reference to support that 1. More percentage of PD patients had exercise than HD patients did 2. Exercise reduce CV mortality or incidents in dialysis patients.

Please clarify the suggestion. Are you asking for data that shows home modalities provide patients with more freedom to exercise which could theoretically lead to better CVD outcomes?

5. The SGLT2i and Kerendia reduce CV risk in CKD patients non yet in dislaysis, is there any data about their CV effect on dialysis patients?

This review is focused primarily on the decision of dialysis modality. I am not sure discussing medications adds to the overall aim.

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Author,

It is an interesting and useful article for clinical practice.  It is very important to know the implications of of dialysis modality on cardiovascular events and mortality.

Observation: Maybe it would be useful to analyze cardiovascular risk factors in dialysis patients according to age.

Kind regards,

Author Response

Thank you for the suggestion. This is addressed in the review by Shah et al. 

Shah S, Weinhandl E, Gupta N, Leonard AC, Christianson AL, Thakar CV. Cardiovascular Outcomes in Patients on Home Hemodialysis and Peritoneal Dialysis. Kidney360 2024;5(2):205-215. DOI: 10.34067/KID.0000000000000360.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Accept.

Congratulations.

Author Response

Reviewer 1 Comments and Suggestions for Authors: Accept. Congratulations. - Thank you!    

Reviewer 2 Report

Comments and Suggestions for Authors

1.      I think the whole narrative review is still short of sufficient citations, let’s try the following paragraph Section 7

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7. Anemia, Uremia, and Chronic Inflammation  

Other mechanisms affecting cardiac outcomes include anemia, residual uremic toxins, and chronic inflammation. Severity of anemia correlates with left ventricular hypertrophy. However, exposure to erythropoiesis-stimulating agents has risks of hypertension and increased blood viscosity, which can also cause downstream effects on cardiovascular health.  

Uremic toxins may contribute to down regulation of Klotho levels³³. Low serum Klotho may increase susceptibility to vascular calcification and cardiac fibrosis. Increasing the frequency of dialysis can reduce residual uremic toxins. However, frequent hemodialysis has (arguably) been associated with a more rapid loss of residual kidney function (RKF). It is postulated that the increased residual uremic toxins may stimulate kidneys, suggesting a benefit of incremental dialysis in those with RKF given that RKF has a strong correlation with survival benefit in dialysis studies.

 

I turn the background to yellow to show that this is a spot where the author should do citation to support this sentence. The ideas are different between these sentiences. And all the other paragraphs are like these (short of sufficient citation support.).

 

2.      If the focus of this review is on the CV risk among different dialysis modalities, the title “Cardiovascular disease in dialysis patients” maybe too wide and ambiguous? How about “The impact of dialysis modalities on cardiovascular risks.” Or other Title more specific to your narrative review?

Author Response

Reviewer 2 Comments:

1. I think the whole narrative review is still short of sufficient citations, let’s try the following paragraph Section 7.
   1. This section and others were expounded upon and edited to include more citations. 
2. If the focus of this review is on the CV risk among different dialysis modalities, the title “Cardiovascular disease in dialysis patients” maybe too wide and ambiguous? How about “The impact of dialysis modalities on cardiovascular risks.” Or other Title more specific to your narrative review?
   1. Title was changed.