Obesity and Chronic Kidney Disease: A Comprehensive Review of Mechanisms, Impact, and Management Strategies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article entitled "Obesity and Chronic Kidney Disease: A Comprehensive Review of Mechanisms, Impact, and Management Strategies" is an interesting topic in CKD patients. 

Some comments for the authors. 

The article is interesting, well-written, and covers the essential aspects of obesity treatment and factors of progression and/or complications related to CKD. However, the manuscript lacks bibliographic references for the studies discussed.  In order for the review to be useful to readers, the authors must complete the references for the studies mentioned (i.e. lines 90, 125, 158, 210-214, 425). Complete the missing references throughout the manuscript.
Likewise, in the section Chronic Inflammatory State, and also in the section Risk Factors and Epidemiological Evidence in obesity, only one bibliographic reference is included. However, the text refers to ‘studies’.

 

Author Response

Author’s Responses to Reviewer 1 Comments

We sincerely thank the reviewer for their thoughtful and constructive feedback. We appreciate the recognition of the manuscript as interesting, well-written, and covering the essential aspects of obesity treatment and its relationship to chronic kidney disease (CKD). Below we provide a point-by-point response to the concerns raised:

Comment 1:

“The manuscript lacks bibliographic references for the studies discussed. In order for the review to be useful to readers, the authors must complete the references for the studies mentioned (i.e. lines 90, 125, 158, 210–214, 425). Complete the missing references throughout the manuscript.”

Author Response:

Thank you for pointing this out. We have thoroughly reviewed the manuscript and inserted the appropriate bibliographic references for the studies discussed in the indicated sections:

• Line 90: This line has changed to line 100 in the revised manuscript. Citation added. [15] [16] [17].
• Line 125: This line has changed to line 135 in the revised manuscript. References included [17] [15]
• Line 158: This line has changed to line 170 in the revised manuscript. References included  [24] [25].
• Lines 210–214: This line has changed to line 223 in the revised manuscript. Multiple references have been added:  [31] [32] [33]
• Line 425: This line has changed to line 438 in the revised manuscript. The reference for long-term outcomes in bariatric surgery and renal function has now been included: [63].

Additionally, we have reviewed the full manuscript and ensured that all other statements referencing studies are now properly supported with citations.

Comment 2:

“In the section ‘Chronic Inflammatory State’, and also in the section ‘Risk Factors and Epidemiological Evidence in Obesity’, only one bibliographic reference is included. However, the text refers to ‘studies’.”

Author Response:

We appreciate this observation. In response:

• In the ‘Chronic Inflammatory State’ section, we have now included additional references:  [19] [14] [20].

 

• In the ‘Risk Factors and Epidemiological Evidence in Obesity’ section, we have added several epidemiological studies that substantiate the prevalence data and risk correlations mentioned. Please see below:

Multiple large-scale studies have shown obesity to be a significant risk factor for CKD development and progression to ESRD [17] [15].

We agree these additions will enhance the manuscript’s utility and reliability for readers.

 

Reviewer 2 Report

Comments and Suggestions for Authors

Reviewer comments are attached to a separate Word file

Comments for author File: Comments.pdf

Author Response

Author’s Responses to Reviewer 2 Comments

We sincerely thank the reviewer for their thoughtful and constructive feedback.

Reviewer comment 1:

• Elaborate on the association between obesity and CVD-mediated CKD progression, as well as post-COVID modifications in CKD severities. However, the authors could improve the manuscript by briefly comparing their approach to other known CVD complications in CKD

Author’s response:

We thank the reviewer for this insightful suggestion. While a broader comparison with other known CVD complications in CKD is indeed valuable, our current manuscript is specifically focused on the association between obesity mediated CKD progression. To maintain clarity and focus, we have limited the scope accordingly. That said, we agree that a comparative analysis would enrich the context and depth of understanding, and we will certainly consider incorporating this perspective in our future work.

Reviewer Comment 2: 

Section 2. Pathogenesis: the vital mechanism and its molecular signaling pathway are missing, which may help elucidate the best way to illustrate the diagrammatic representations.

Author’s response:

We thank the reviewer for this valuable comment. In response, we have revised Section 2 to include a detailed description of the key molecular signaling pathways involved in the pathogenesis, which we believe enhances both the clarity and the scientific depth of the section. Please see details:

It also activates the PI3K/Akt/mTOR pathway [9], leading to glomerular hyperfiltration and podocyte dysfunction. Additionally, the renin-angiotensin-aldosterone system (RAAS) is upregulated in obesity, resulting in increased sodium retention, elevated intraglomerular pressure, and subsequent renal fibrosis.

Inflammation plays a central role in this pathophysiological cascade. Adipose tissue macrophage infiltration leads to overexpression of pro-inflammatory cytokines such as TNF-α, IL-6, and MCP-1, which activate the NF-κB signaling pathway, promoting tubulointerstitial fibrosis and oxidative stress [10]. The JAK/STAT pathway is also implicated in mediating cytokine-induced inflammation and cellular apoptosis within the renal parenchyma [10].

Reviewer comment 3: 

Page No.2 line-57 “These cells release a wide array of biologically active compounds.” Those are not compounds; they are all key factors that need to be corrected

Author’s response:

We appreciate the reviewer’s careful observation. We have revised the sentence to accurately reflect the nature of the substances released by these cells. The term "biologically active compounds" has been replaced with "biologically active key factors" to ensure scientific accuracy. Please see below:

These cells release a wide array of biologically active key factors, including cytokines, leptins, adiponectins, and tumor necrosis factor-α (TNF-α), that cause systemic inflammation [7].

Reviewer comment 4: 

Most abbreviations at first need to mention the full form with the abbreviation: for example, what does NHANES, etc?

Author’s response:

Thank you for pointing this out. We have carefully reviewed the manuscript and ensured that all abbreviations, including NHANES (National Health and Nutrition Examination Survey), are defined in full upon their first mention for clarity and consistency. Please see below:

Based on 2011–2014 National Health and Nutrition Examination Survey (NHANES) data, almost half (44.1%) of those with CKD also had obesity (BMI > 30 kg/m²), compared to an overall obesity prevalence in the same dataset of around 38%.

Reviewer comment 5: 

Figure 2, the authors mentioned that the source, adapted from “Kreiner, 155 F.F., et al., Obesity-Related Kidney Disease: Current Understanding and Future Perspectives. 156 Biomedicines, 2023. 11(9) [17]” needs to mention the copyrights. As well as figure 3.

Author’s response:

We thank the reviewer for this important observation. We have updated the captions for Figures 2 and 3 to include the appropriate copyright information and ensure compliance with attribution requirements. Please see below:

 

Figure 2.  Pathophysiological associations and therapeutic options in obesity-related kidney disease.  This figure shows the known or suspected obesity-related risk factors (yellow box) directly or indirectly implicated in the development of chronic kidney disease (CKD). Reproduced from Kreiner, F.F., et al., Obesity-Related Kidney Disease: Current Understanding and Future Perspectives. Biomedicines, 2023. 11(9) [23]. This article is published under the Creative Commons Attribution (CC BY 4.0) license, which permits reproduction with proper attribution.

 

Figure 3. Illustration of the obesity paradox. Obesity is a risk factor for chronic kidney disease (CKD), yet it protects against CKD-associated death. ESRD, end-stage renal disease. Reproduced from Kalantar-Zadeh, K., et al., The Obesity Paradox in Kidney Disease: How to Reconcile it with Obesity Management. Kidney Int Rep, 2017. 2(2): p. 271-281 [27]. This article is available under the Creative Commons CC BY-NC-ND 4.0 license, which permits non-commercial reproduction without modification, provided full attribution is given.

We sincerely thank the reviewer for their valuable feedback, which has helped us improve the quality and clarity of our manuscript.

 

 

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Missing originality, it needs to revise the manuscript (29% SIMILARITY INDEX), and it needs to reduce less than 15% for good scientific writing.

All other queries are acceptable

Comments for author File: Comments.pdf

Author Response

Reviewer comment:

“Missing originality, it needs to revise the manuscript (29% SIMILARITY INDEX), and it needs to reduce less than 15% for good scientific writing.”

Author Response:

We would like to specifically address the concerns raised by Reviewer 2, particularly regarding the reported similarity index of 29%. As you are aware, we have thoroughly re-evaluated our manuscript and are confident that it adheres to all scientific and ethical standards. The manuscript has been comprehensively written, remains clinically relevant, and includes appropriate citations for all referenced material.

It appears that this report is flagging standard medical terminology and widely accepted scientific phrases, many of which are required elements of a review article and submission templates. Below are examples of terms and phrases this report has flagged:

• Clinical terms and disease states: Diabetes, BMI >30, Dialysis, CKD, Cirrhosis, Obesity-related glomerulopathy, Heart failure

• Medications and treatment classes: GLP-1 receptor agonists, SGLT2 inhibitors, Semaglutide, Orlistat

• Scientific acronyms and organizations: KDOQI, KDIGO, CDC, NHANES, USRDS, RAAS

• Standard terminology and metrics: GFR (glomerular filtration rate), UACR, very low-calorie diet

• Landmark studies: Inclusion of established data such as hazard ratios and confidence intervals, appropriately cited

Some flagged phrases even include copyright statements, if we alter or omit universally accepted terminology, it could compromise the scientific accuracy of the manuscript. We believe the suggestions to remove or rephrase these standard terms are neither practical nor appropriate for a scholarly review article.

We sincerely hope you understand our position and the basis for our concerns. Please feel free to reach out if you have any questions or need additional clarification.

Sincerely,

Kunal Sonavane, MD, MPH

(On behalf of all co-authors)

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

none