Frailty in Older Patients with End-Stage Renal Disease and Undergoing Chronic Haemodialysis in Vietnam

Round 1

Reviewer 1 Report

This study addresses a relevant topic in geriatric populations: the association between frailty and mortality in people with end-stage renal disease and undergoing chronic dialysis. We consider to clarify some relevant findings in the manuscript:

1) Some factors frequently associated with mortality in this kind of patients did not result significantly associated with death in this study. This is the case of dialysis duration or diabetes. Please comment within discussion.

2) It looks like this study was powered to detect a difference of mortality between frail vs non-frail patients. However, a lot of considerations are done with regards to the different categories of CFS and mortality in the text. These considerations about the association between CFS category and mortality, even when interesting, should be taken with caution, due to limitations in power. Please discuss this within limitations.

3)  Fig 2 shows survival curves across the different frailty groups. The corresponding text brings a significant p value that can be misunderstood by the readers. This p value is a 'global' one but does not reflects how the curves differ one vs each other. We assume that just the 'extreme' curves explain the significance found with the log-rank text (due to the limited power to detect inter-CFS category differences). This should be clearly explained within the text.

   

Just minor editing of English suggested

Author Response

We would like to thank you for the time spent reviewing our manuscript and for your useful comments, which has helped improve our manuscript a lot.

We have specifically responded to the issues raised as detailed below and would be happy to address any further issues if required.

This study addresses a relevant topic in geriatric populations: the association between frailty and mortality in people with end-stage renal disease and undergoing chronic dialysis. We consider clarifying some relevant findings in the manuscript:

• Some factors frequently associated with mortality in this kind of patients did not result significantly associated with death in this study. This is the case of dialysis duration or diabetes. Please comment within discussion.

Response: We think this is probably due to the small sample size of the study. Moreover, most of the participants had analysis duration <=1 year.

• It looks like this study was powered to detect a difference of mortality between frail vs non-frail patients. However, a lot of considerations are done with regards to the different categories of CFS and mortality in the text. These considerations about the association between CFS category and mortality, even when interesting, should be taken with caution, due to limitations in power. Please discuss this within limitations.

Response: We have added this in the limitation part (lines 332-336)

• Fig 2 shows survival curves across the different frailty groups. The corresponding text brings a significant p value that can be misunderstood by the readers. This p value is a 'global' one but does not reflect how the curves differ one vs each other. We assume that just the 'extreme' curves explain the significance found with the log-rank text (due to the limited power to detect inter-CFS category differences). This should be clearly explained within the text.

Response: We have now added these in the text (lines 271-274): The p-values for comparisons between participants with CFS 4-5 versus participants with CFS ≤ 3: 0.643, participants with CFS 6 versus participants with CFS ≤ 3: 0.312, participants with CFS ≥ 7 versus participants with CFS ≤ 3: 0.036.

Reviewer 2 Report

Frailty in older patients with end-stage renal disease and undergoing chronic dialysis in Vietnam

The manuscript describes a non interventional observation study of 6 month duration with a convenience cohort of elderly patients undergoing hemodialysis in two centers in a single Vietnam city.

Major issues are with clarity.

Line 35-48.  Consider re-writing definition of CKD consistent within text.  Line 35 – characterized as an “incurable disease”.  CKD is more accurately defined as a progressive medical condition since the etiology is multifactorial.  Avoid using “chronic kidney disease” and “disease” within the same sentence.

Methodology

The manuscript is lacking information on:

1.       How data was collected for the frailty index.  The text describes the categories of score CFS 1-9 but fails to say “who” graded the patient and how consensus was reached if more than one person scored the CFS (good clinical practice would have been for more than one practitioner to rate)

2.       Information on number of possible patients compared to those that actually were analyzed for the study (eliminated those who did not give consent and those who met exclusion criteria).  See Line 158: 175 patients were recruited

3.       Line 131 – Co morbidities were assessed using a pre-defined list.  Information is missing on how this list was created and what is contained.

4.       More information on dialysis itself in Vietnam. Is “dialysis” hemodialysis or peritoneal dialysis? It is this covered for all individuals or only those with private insurance (important from a treatment bias perspective and if delay in treatment is related to cost). What is the goal of dialysis, i.e., Kt/V. Duration is in the table but not the degree of dialysis adequacy as a goal.

Results/Discussion

1.       How does the study population compare to the total Vietnam CKD/hemodialysis population? For example, the level of low body weight (BMI, malnutrition?) is statistically significant between categories, and greater than the US population.  Much of the literature on fraility provided as references is on non-asian CKD patients whose BMI is much higher a start of dialysis.  Is this a confounding biased variable? (line 241)

2.       Authors infer diabetes is a driving factor in CKD in Vietnam. The data shows that age and low body weight may be driving fraility as defined by this study greater than diabetes.  Authors should provide more text to support their statement on diabetes.

 

 

 

 

 

 

Author Response

We would like to thank you for the time spent reviewing our manuscript and for your useful comments, which has helped improve our manuscript a lot. We have specifically responded to the issues raised as detailed below and would be happy to address any further issues if required.

Frailty in older patients with end-stage renal disease and undergoing chronic dialysis in Vietnam. The manuscript describes a non interventional observation study of 6 month duration with a convenience cohort of elderly patients undergoing hemodialysis in two centers in a single Vietnam city.

Major issues are with clarity.

Line 35-48.  Consider re-writing definition of CKD consistent within text.  Line 35 – characterized as an “incurable disease”.  CKD is more accurately defined as a progressive medical condition since the etiology is multifactorial.  Avoid using “chronic kidney disease” and “disease” within the same sentence.

Response: We have revised accordingly (line 36).

Methodology

The manuscript is lacking information on:

1. How data was collected for the frailty index.  The text describes the categories of score CFS 1-9 but fails to say “who” graded the patient and how consensus was reached if more than one person scored the CFS (good clinical practice would have been for more than one practitioner to rate)

Response: We have now added this information in the manuscript (lines 132-134)

2. Information on number of possible patients compared to those that actually were analyzed for the study (eliminated those who did not give consent and those who met exclusion criteria).  See Line 158: 175 patients were recruited

Response: We have now added this information in the manuscript (lines 215-218)

3. Line 131 – Co morbidities were assessed using a pre-defined list.  Information is missing on how this list was created and what is contained.

Response: We have now added this information in the manuscript (lines 184-188)

 

4. More information on dialysis itself in Vietnam. Is “dialysis” hemodialysis or peritoneal dialysis? It is this covered for all individuals or only those with private insurance (important from a treatment bias perspective and if delay in treatment is related to cost). What is the goal of dialysis, i.e., Kt/V. Duration is in the table but not the degree of dialysis adequacy as a goal.

Response: The study population are older patients with chronic hemodialysis. We have added this in the manuscript. Dialysis is covered by public health insurance for all individuals.

Results/Discussion

1. How does the study population compare to the total Vietnam CKD/hemodialysis population? For example, the level of low body weight (BMI, malnutrition?) is statistically significant between categories, and greater than the US population.  Much of the literature on frailty provided as references is on non-asian CKD patients whose BMI is much higher a start of dialysis.  Is this a confounding biased variable? (line 241)

Response: We don’t have information on the characteristics of the total Vietnam CKD/hemodialysis population. However, we have provided comparisons to several studies conducted in patients with CKD in Vietnam (lines 288-295). We have added the BMI variable in Table 2: Univariate analysis showed a non-significant association with the study outcome. It is unlikely that it could be a confounding variable in this study.

 

2. Authors infer diabetes is a driving factor in CKD in Vietnam. The data shows that age and low body weight may be driving frailty as defined by this study greater than diabetes.  Authors should provide more text to support their statement on diabetes.

Response: 62.9% of our study sample had diabetes. Our study was designed to examine the prevalence of frailty in older patients with ESRD on hemodialysis and the predictive value of frailty for mortality, not to examine the predictors for frailty.

Round 2

Reviewer 2 Report

The paper has been extensively revised by the author group to more clearly describe the research design, data collection, and general methodology.  I have no further edit concerns or recommendations.