Vascular Calcification in Diabetic Kidney Disease
Round 1
Reviewer 1 Report
This review article considers the role of diabetes mellitus in vascular calcification, with a particular focus on diabetic kidney disease. The article is well written and is a valuable addition to existing literature. The conclusions of the paper reflect the message of the review.
To be published, it requires improvement by addressing a few minor concerns:
1) The article is written in an English that needs minor improvements.
For example, please check that abbreviations are not provided more than once e.g. chronic kidney disease is abbreviated to CKD on lines 8 and lines 14. The abbreviation for bone morphogenic protein is also provided more than once.
The following sentence on lines 32-35 would also benefit from rewriting: ‘This leads to a decrease in arterial compliance and an increase of the pulse wave velocity; VC is a critical cause of cardiovascular disease and death; peripheral artery disease affects more than 8.5 million people in the United States, approximately one third of whom have comorbid diabetes [4]’.
Line 36 – ‘Adipokines as leptin…’ should read ‘Adipokines such as leptin…’
2) References – please double check references through manuscript. In particular, the references provided in section 2 (lines 44-55) do not appear to be correct for the corresponding text.
3) Lines 52-53 - I would argue that CBFA1 is a transcription factor regulating osteogenesis, and not ‘a large bone related protein’.
4) Line 77 – I think you meant protein kinase C (PKC), opposed to protein C kinase (PCK)?
5) Line 182 – Provide reference for ‘RANKL-RANK binding then stimulates osteoclast differentiation’.
6) Line 199 – ‘…..will double to 300 million people by 2025’. This prediction will be out of date in a couple years, so could you provide a longer term (i.e. 5-10 year) prediction instead?
7) Line 242 – I am not familiar with parathormon being the usual term used for PTH?
8) Line 278 - Provide reference for ‘The transformation from CPP I to CPP II is 276 under several mineral metabolism factors such as the serum concentration of phosphorus, fetuin-A, Ca2+ and Mg2+’.
9) Figure 1 – the H&E image in this Figure is not providing any useful information so I would suggest that it is removed. If the image is kept, a reference for this figure must be provided. Furthermore, the H&E image is of poor quality and should be replaced with a higher resolution image if kept.
Author Response
Reviewer 1
1) The article is written in an English that needs minor improvements.
For example, please check that abbreviations are not provided more than once e.g. chronic kidney disease is abbreviated to CKD on lines 8 and lines 14. The abbreviation for bone morphogenic protein is also provided more than once.
Response:
Dear Reviewer,
The abbreviation CKD is defined in line 2 of the abstract. If you agree, it will be kept for the line 8,14.
We corrected the abbreviation for BMP.
The following sentence on lines 32-35 would also benefit from rewriting: ‘This leads to a decrease in arterial compliance and an increase of the pulse wave velocity; VC is a critical cause of cardiovascular disease and death; peripheral artery disease affects more than 8.5 million people in the United States, approximately one third of whom have comorbid diabetes [4].
Response:
The sentence has been changed: This leads to decreased arterial compliance and increased pulse wave velocity; VC is a critical cause of cardiovascular disease and death; peripheral arterial disease affects more than 8.5 million people in the United States; DM affects one-third of these patients.
Line 36 – ‘Adipokines as leptin…’ should read ‘Adipokines such as leptin…’
Response:
The sentence has been changed: Adipokines such as leptin
2) References – please double check references through manuscript. In particular, the references provided in section 2 (lines 44-55) do not appear to be correct for the corresponding text.
Response:
Dear Reviewer, we modified the references.
3) Lines 52-53 - I would argue that CBFA1 is a transcription factor regulating osteogenesis, and not ‘a large bone related protein.
Response:
The sentence has been changed: these osteoblastic-like cells synthesize transcription factors regulating osteogenesis, such as core-binding factor a1 (Cbfa1).
4) Line 77 – I think you meant protein kinase C (PKC), opposed to protein C kinase (PCK)?
Response:
The sentence has been modified.
5) Line 182 – Provide reference for ‘RANKL-RANK binding then stimulates osteoclast differentiation’.
Response:
We provided a new reference:
Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation, H. Park, N. K. Lee and S. Y. Lee, Mol Cells 2017
6) Line 199 – ‘…..will double to 300 million people by 2025’. This prediction will be out of date in a couple years, so could you provide a longer term (i.e. 5-10 year) prediction instead?
Response:
We provided new data in the text: The prevalence of diabetes secondary to obesity will raise by 783 million people by 2045 according to the Internationnal Diabetes Federation Atlas Tenth edition 2021
7) Line 242 – I am not familiar with parathormon being the usual term used for PTH?
Response:
We added PTH.
8) Line 278 - Provide reference for ‘The transformation from CPP I to CPP II is 276 under several mineral metabolism factors such as the serum concentration of phosphorus, fetuin-A, Ca2+ and Mg2+’.
Response.
Wald, J., Wiese, S., Eckert, T., Jahnen-Dechent, W., Richtering, W., & Heiss, A. (2011). Formation and stability kinetics of calcium phosphate–fetuin-A colloidal particles probed by time-resolved dynamic light scattering.
9) Figure 1 – the H&E image in this Figure is not providing any useful information so I would suggest that it is removed. If the image is kept, a reference for this figure must be provided. Furthermore, the H&E image is of poor quality and should be replaced with a higher resolution image if kept.
Response:
This image comes from our experimental laboratory; unfortunately, I cannot provide a better resolution. We added a reference. Finally, if it is the wish of the reviewers and the editor, we agree to remove this figure.
Reviewer 2 Report
In the work entitled: “Accelerated Vascular Calcification in Diabetic Kidney Disease”, the authors mention the title: “Accelerated Vascular Calcification”, in the summary and conclusions they refer to the progression of calcification, however, the authors explain in the text separately the processes of calcification and oxidative stress and proinflammatory state and hypertension and chronic. kidney disease, and not the progression of vascular calcification in diabetic kidney disease. In other words, studies mostly do not show the risk factors that affect the accelerated or slow progression of calcification in diabetics over time.
It is recommended: Include studies indicating the risk factors associated with accelerated, slow, or no calcifications over time in Diabetic Kidney Disease patients,
The references: 11, 37,40, are not correct. Update references.
Indicate the advances in the knowledge of calcification specifying which were in experimental models: in vitro and in vivo and which in diabetic kidney disease patients.
I recommended the following references: DOI: 10.1159/000477380 and doi.org.10.3390/biom12040551
Author Response
Reviewer 2
In the work entitled: “Accelerated Vascular Calcification in Diabetic Kidney Disease”, the authors mention the title: “Accelerated Vascular Calcification”, in the summary and conclusions they refer to the progression of calcification, however, the authors explain in the text separately the processes of calcification and oxidative stress and proinflammatory state and hypertension and chronic. kidney disease, and not the progression of vascular calcification in diabetic kidney disease. In other words, studies mostly do not show the risk factors that affect the accelerated or slow progression of calcification in diabetics over time.
It is recommended: Include studies indicating the risk factors associated with accelerated, slow, or no calcifications over time in Diabetic Kidney Disease patients,
Response:
We thank the reviewer for these remarks and comments. In our review, we have attempted to present studies witch demonstrate that diabetes is associated with a higher risk of vascular calcifications. We also thank the reviewer for pointing out that factors associated with chronic renal failure increase this risk. We agree that it is important to clarify which factors are associated with rapid progression of vascular calcifications. It is often difficult to define them precisely, although in chronic renal failure, hyperphosphataemia is probably a major factor.
The references: 11, 37,40, are not correct. Update references.
Response
We have made the requested changes for these references 11, 37, 40.
Indicate the advances in the knowledge of calcification specifying which were in experimental models: in vitro and in vivo and which in diabetic kidney disease patients.
Response:
Dear reviewer, In this article, we have attempted to present the factors associated with diabetes based on in vitro and in vivo studies. In order to clarify whether these were clinical studies, we have endeavoured to specify this in the text in the hope of responding to the reviewers' request
I recommended the following references: DOI: 10.1159/000477380 and doi.org.10.3390/biom12040551
Response:
We have followed the recommendations to add the following references DOI: 10.1159/000477380 and doi.org.10.3390/biom12040551.
Reviewer 3 Report
The manuscript says that Diabetic Mellitus patients with CKD have an increased risk of developing vascular calcification (VC) compared to patients with only CKD. This article discusses how hyperglycemia and its associated factors promote VC and the current treatment options. The manuscript is well written and is accepted after minor revision.
1) The authors discussed several calcification inhibitors from lines 48 to 55. Where are the relevant evidence or references?
2) Lines 168 to 170 authors describe numerous NO studies; however, the authors provided just one reference.
3) Lines 178 to 180, what is OPG?
4) Line 190 to 191. The authors have to provide the functions of Kupffer cells.
Author Response
Reviewer 3
The manuscript says that Diabetic Mellitus patients with CKD have an increased risk of developing vascular calcification (VC) compared to patients with only CKD. This article discusses how hyperglycemia and its associated factors promote VC and the current treatment options. The manuscript is well written and is accepted after minor revision.
1) The authors discussed several calcification inhibitors from lines 48 to 55. Where are the relevant evidence or references?
Response:
We thank the reviewer for these remarks and comments. The description of these different calcification inhibitors seemed useful to our opinion to introduce the paragraph 3.6 (Chronic Kidney Disease-Bone Disorder (CKD-MBD), microRNAs, calciprotein particles and diabetes) which details the assessment of the severity of CV in CKD patients by T50.
2) Lines 168 to 170 authors describe numerous NO studies; however, the authors provided just one reference.
Response:
We added 2 additional references
Mizutani K, J Hypertens 2000
Hirafuji M, Life Sci. 2002,
3) Lines 178 to 180, what is OPG?
Response
We have added in the text osteopontogerin with the abbreviation OPG.
4) Line 190 to 191. The authors have to provide the functions of Kupffer cells.
Response
As request, we added a sentence about the functions of Kuppffer cells
Round 2
Reviewer 2 Report
Dear Authors:
1. Please, delete the word acceleration or progression unless you want to say the changes in calcification (Deltas) in a given time.
2. Despite the fact that you put the references that I suggested, thanks.
Authors can present more studies that comprehensively involve Vascular Calcification in diabetes with chronic kidney disease.
For example; On page 5 line 253 there is actually more information about it.
One suggestion is to change the title to "Diabetes associated with higher risk of Vascular calcification". As you mentioned in your previous answers.
3. Check again that all references are correct
Author Response
Reviewer 2
1, 2, 3 :
Dear Reviewer,
As request, we have changed the title even if several authors in the literature use the expression: accelerated vascular calcification associated with diabetes. We wanted to keep the word kidney as it is a journal of nephrology.
We did not wish to add new references to the various in vivo and in vitro studies cited in our article in order to avoid repetitions.
Best regards,
Olivier Phan
