The Relationship of Macro–Micronutrient Intake with Incidence and Progressivity of Hypertension and Microalbuminuria

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a timely and clinically relevant topic, given the growing recognition of nutritional factors in the pathogenesis of hypertension and early kidney injury. The authors have clearly undertaken an extensive literature search and present a wide-ranging discussion of macro- and micronutrients. However, in its current form, the manuscript reads more as a descriptive compilation than a critical review, and several key areas need strengthening before it is suitable for publication.

Major Concerns

1. Abstract
The abstract requires substantial rewriting for clarity and conciseness. At present, it reads as a long descriptive overview rather than a structured summary. A high-quality abstract should emphasize:

• The rationale for reviewing nutrient intake in relation to hypertension and microalbuminuria.

• A succinct summary of the most consistent evidence (e.g., sodium restriction, potassium intake, protein moderation, vitamin D).

• Identification of areas where evidence remains contradictory or insufficient.

• Practical implications for clinical practice.

This restructuring will make the abstract more informative and clinically relevant.

2. Lack of Critical Analysis
Much of the manuscript summarizes individual studies without integrating or appraising the findings. Contradictory results are presented without reconciliation. For example, Vitamin A is described as protective in some contexts and harmful in others, but there is no effort to contextualize these discrepancies in terms of population studied, dosage, or mechanistic plausibility. A stronger synthesis is needed, with a clear discussion of areas of consensus and acknowledgment of where evidence remains weak.

3. Scope is Overly Broad
The review attempts to cover nearly every nutrient in relation to hypertension and microalbuminuria, which makes it read more like a textbook chapter than a focused scholarly article. Narrowing the scope to nutrients with the strongest and most consistent evidence (e.g., sodium, potassium, protein, vitamin D, antioxidants) would sharpen the central message and increase its impact.

4. Redundancy and Length
Several sections—particularly those on vitamins—are repetitive, with detailed mechanistic descriptions that dilute key points. The manuscript is overly long for a narrative review and would benefit from substantial condensation and clearer thematic organization.

5. Limited Clinical Translation
Although mechanisms are extensively discussed, practical clinical guidance is underdeveloped. A concise section contrasting nutrients with consistent evidence versus those with conflicting or insufficient evidence would greatly enhance clinical utility and provide actionable take-home points for clinicians.

6. Imbalance Between Hypertension and Microalbuminuria
Hypertension is comprehensively covered, but the section on microalbuminuria is less developed. Evidence linking nutrients to MA is patchier, and the authors should be explicit about where data are preliminary or speculative. A more balanced discussion would improve the manuscript.

Minor Concerns

• Language and Grammar: The manuscript contains multiple awkward or incomplete sentences (e.g., “CKD is one of the most common complication of hypertension”). A thorough language edit is required to correct grammar, syntax, and flow.

• Referencing: References are abundant but not critically appraised. Recent systematic reviews and meta-analyses (2023–2025) should be emphasized more heavily than older single-center studies.

• This is a suggestion( not a recommendation)- if the authors have access to textbook references like Nutritional Management of Renal Disease
  This would strengthen the scholarly foundation- however, I do understand it's a large textbook!

• Formatting: Long paragraphs, especially in the vitamin and mineral sections, should be broken into shorter, thematically coherent subsections to improve readability.

Comments on the Quality of English Language

stated above

Author Response

Major concerns

1. The abstract requires substantial rewriting for clarity and conciseness. At present, it reads as a long descriptive overview rather than a structured summary.
   Thank you for this excellent suggestion. We agree that the original abstract was not sufficiently structured. Therefore, the abstract has been completely rewritten. This new structure now provides a concise summary of the review’s main conclusions, highlights areas of consensus versus controversy, and offers a better clinical takeaway.

2. Much of the manuscript summarizes individual studies without integrating or appraising the findings. Contradictory results are presented without reconciliation. For example, Vitamin A is described as protective in some contexts and harmful in others, but there is no effort to contextualize these discrepancies in terms of population studied, dosage, or mechanistic plausibility. A stronger synthesis is needed, with a clear discussion of areas of consensus and acknowledgment of where evidence remains weak.
   We have thoroughly revised the manuscript to move from simple reporting to critical interpretation. As suggested, we have synthesized better analysis for the evidence and give comparison where the evidence is conflicting.

4.  Scope is Overly Broad with Redundancy and Length issues
   The review attempts to cover nearly every nutrient in relation to hypertension and microalbuminuria, which makes it read more like a textbook chapter than a focused scholarly article. Narrowing the scope to nutrients with the strongest and most consistent evidence (e.g., sodium, potassium, protein, vitamin D, antioxidants) would sharpen the central message and increase its impact.
   Several sections—particularly those on vitamins—are repetitive, with detailed mechanistic descriptions that dilute key points. The manuscript is overly long for a narrative review and would benefit from substantial condensation and clearer thematic organization.
   Thank you very much for the comments. To address this, we have performed a major restructuring of the entire manuscript based on a tiers of evidence (strong evidence, promising but inconsistent evidence, and emerging or highly controversial evidence).
5. Major Concern 5: Limited Clinical Translation.
   Although mechanisms are extensively discussed, practical clinical guidance is underdeveloped. A concise section contrasting nutrients with consistent evidence versus those with conflicting or insufficient evidence would greatly enhance clinical utility and provide actionable take-home points for clinicians.
   We thank the reviewer for this valuable suggestion to improve the manuscript's practical impact. To provide the clear, scannable recommendations requested, we have added two new summary tables: Table 2 for key components and health effects of major dietary patterns on HTN and MA and Table 3 for summary of evidence and clinical recommendations for individual nutrients for HTN and MA.
6. Major Concern 6: Imbalance between the discussion of Hypertension (HTN) and Microalbuminuria (MA).
   Hypertension is comprehensively covered, but the section on microalbuminuria is less developed. Evidence linking nutrients to MA is patchier, and the authors should be explicit about where data are preliminary or speculative. A more balanced discussion would improve the manuscript.
   The reviewer correctly points out that the evidence base for nutrition and MA is less developed than for HTN. We have revised the manuscript to be more transparent about this evidence gap.

 

Minor concerns

1. Language and Grammar: The manuscript contains multiple awkward or incomplete sentences (e.g., “CKD is one of the most common complication of hypertension”). A thorough language edit is required to correct grammar, syntax, and flow.
   The entire manuscript has undergone a language editing to correct grammatical errors and improve clarity and flow.
2. Referencing: References are abundant but not critically appraised. Recent systematic reviews and meta-analyses (2023–2025) should be emphasized more heavily than older single-center studies.
   We have reviewed our citations and prioritized the "hierarchy of evidence" by ensuring that major claims are supported by the most recent and impactful systematic reviews and meta-analyses.
3. Formatting: Long paragraphs, especially in the vitamin and mineral sections, should be broken into shorter, thematically coherent subsections to improve readability.
   Thank you for the suggestion. We have revised the long text into shorter, more focused paragraphs to significantly improve readability.

Reviewer 2 Report

Comments and Suggestions for Authors

The effects on hypertension and microalbuminuria are listed in Table 2. Table 2 should be simplified by separating effects into those that lower or may lower hypertension and microalbuminuria, making it easier to understand.

Example

Nutrient	Effects on Hypertension	Effects on microalbuminuria
Potassium	lowers blood pressure	may decrease

Furthermore, since each component does not have an equal effect, is it appropriate to list them in parallel? It would be better to create Table 3, distinguishing them into two groups: strong evidence and possible evidence.
For example, how about dividing them into two groups: those with strong evidence like sodium, potassium, calcium, magnesium, and Vitamin E, and those with weak evidence like Vitamin C?

Author Response

1. The effects on hypertension and microalbuminuria are listed in Table 2. Table 2 should be simplified by separating effects into those that lower or may lower hypertension and microalbuminuria, making it easier to understand.
   We thank the reviewer for this excellent suggestion to improve clarity. We agree that the original table was too dense. We have completely revised Table 2 (now Table 3) to be more concise as suggested.
2. It would be better to create Table 3, distinguishing them into two groups: strong evidence and possible evidence.
   Thank you for the insightful comment. We have fundamentally restructured the entire manuscript to follow a tiers of evidence. In addition, we have added the information to the current Table 3.

Reviewer 3 Report

Comments and Suggestions for Authors

This is a comprehensive review of the impact of some macro- and micronutrients on hypertension and microalbuminuria. Indeed, much still remains unclear about whether it is the single nutrients, the interplay between them, or both, that impact de novo hypertension development as well as worsening existing hypertension and microalbunimuria. The authors are commended on the detailed review of existing data on the topic. Please find below a few points that could in my opinion improve the manuscript.

• When discussing sodium intake, the authors never mention that salt-sensitivity of blood pressure is as important as the sodium intake itself, as it has been linked to occur due to other nutrient intake (i.e. fructose) and due to genetic factors (i.e. some genes have been discovered especially in African American population). Perhaps adding that aspect of hypertension may round out the discussion on both hypertension and microalbuminuria
• The important caveat of which part of the world the nutritional studies have been conducted has also not been mentioned. For example, carbohydrates from vegetables will do different things to the CVD system from the carbohydrates from processed and ultra processed foods. Could the authors perhaps mention if the studies they review mention these details, and perhaps comment on how important it is to increase the granularity of information on nutritional studies for this reason?

Author Response

1. When discussing sodium intake, the authors never mention that salt-sensitivity of blood pressure is as important as the sodium intake itself, as it has been linked to occur due to other nutrient intake (i.e. fructose) and due to genetic factors (i.e. some genes have been discovered especially in African American population).
   Thank you very much for highlighting this important point. We agree that a discussion of salt sensitivity is crucial for a comprehensive review. The manuscript has been significantly revised to incorporate this concept directly within Section 3.1 (Sodium and Potassium). The revised section now includes a discussion on salt sensitivity that covers the specific points.
   
   
2. The important caveat of which part of the world the nutritional studies have been conducted has also not been mentioned. For example, carbohydrates from vegetables will do different things to the CVD system from the carbohydrates from processed and ultra processed foods. Could the authors perhaps mention if the studies they review mention these details, and perhaps comment on how important it is to increase the granularity of information on nutritional studies for this reason?
   Thank you very much for the comment. We have reinforced the importance of nutrient quality and source throughout the review. However, regarding the nature of the studies being reviewed, we have added a discussion acknowledging that this manuscript is largely a review of systematic reviews and meta-analyses. We state that this approach, while providing a high-level overview, is limited by the scope and quality of the primary studies included in those reviews. 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Please verify adherence to the journal’s word limit; if it exceeds the specified threshold, a more concise synthesis—particularly through reduction of overlapping mechanistic discussions—may be warranted.

To strengthen interpretive coherence, consider adding a concluding sentence that explicitly links the evidence hierarchy (strong → conflicting → emerging) to established frameworks of clinical decision-making.

The authors have effectively resolved the substantive concerns raised earlier; the manuscript now demonstrates logical organization, critical synthesis, clinical applicability, and linguistic precision appropriate for publication.

Reviewer 2 Report

Comments and Suggestions for Authors

Authors have performed the corrections and answered the comments in this version. Now I think this paper has improved very much.