Translational Potential: Kidney Tubuloids in Precision Medicine and Regenerative Nephrology

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review your Perspective “Translational potential: Kidney tubuloids in precision medicine and regenerative nephrology.” The manuscript addresses a highly relevant and timely topic, and it is evident that substantial effort has been invested in synthesising a rapidly evolving field. The structure is generally clear, the narrative is engaging, and the focus on translational applications will be of interest to the readership of Pharmaceutics.
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Overall, the article has strong potential, but in its current form, it would benefit from major revisions to improve balance, rigor, and clarity. In particular, I think the manuscript will be significantly strengthened by the following key changes:

1. Add quantitative data and at least one summary table. For several central claims (e.g., “robust transporter expression,” “improved barrier function,” “enhanced maturation”), the reader lacks numbers or direct comparisons (tubuloids vs. native tissue vs. PSC organoids). Including a concise table comparing key functional readouts (transporter expression, TEER, injury markers) and main tubuloid sources (tissue, urine, iPSC) would greatly increase the scientific weight of the review.
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2. Integrate limitations earlier and more explicitly. Sections 2-4 read at times as overly optimistic, whereas a more critical discussion of current constraints (inter-laboratory variability, incomplete maturation, lack of vascular/immune components, regulatory hurdles) appears mainly in Section 5. Bringing some of these issues forward will provide a more balanced and realistic picture.
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3. Clarify what is established versus speculative. The manuscript nicely covers microfluidics, EVs, gene editing, and multi‑omics, but the maturity of these approaches differs. It would help readers if you distinguish more clearly between: (a) applications already demonstrated in tubuloids (e.g., certain toxicity models), (b) proof‑of‑concept uses (e.g., specific CRISPR disease models), and (c) future perspectives (biobanks, digital twins, bioartificial kidneys).
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4. Strengthen and streamline the “computational & multi‑omics” and translational sections. The paragraph on multi‑omics/AI and “digital twins” is interesting but quite general. A bit more concrete detail (one or two specific examples or use‑cases) and, conversely, slightly less promotional wording would make this section more convincing. Likewise, a short paragraph outlining the expected regulatory/validation path (what would be needed for clinical or regulatory use of tubuloid platforms) would align better with the “translational potential” emphasis.
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5. Polish references and language. Some references appear incomplete or inconsistent in format, and a careful check against the journal’s style will be necessary. The English is generally good; a light language edit for minor repetitions and long sentences would further improve readability.
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In summary, this is a promising and timely Perspective that, after a focused revision along the lines above, could serve as a handy reference for researchers and clinicians interested in kidney tubuloids and precision nephrology. I encourage resubmission after revision and look forward to seeing the updated version.

Author Response

Response to Reviewer 1 Comments

 

Reviewer- 1 Comment:

Response:

We sincerely thank Reviewer 1 for the insightful evaluation of our manuscript. We deeply appreciate your time and effort to strengthen our manuscript. In response to your thoughtful suggestions, we have refined the manuscript to further strengthen clarity, coherence, and translational relevance. We trust that these revisions enhance the overall quality and impact of the review. Below, we respond point-by-point and describe the corresponding changes made in the revised version.

 

Comment-1: Add quantitative data and at least one summary table. For several central claims (e.g., “robust transporter expression,” “improved barrier function,” “enhanced maturation”), the reader lacks numbers or direct comparisons (tubuloids vs. native tissue vs. PSC organoids). Including a concise table comparing key functional readouts (transporter expression, TEER, injury markers) and main tubuloid sources (tissue, urine, iPSC) would greatly increase the scientific weight of the review.

 

Response-1:

We sincerely thank the Reviewer-1 for this thoughtful and valuable comment. We agree that the inclusion of quantitative comparisons substantially strengthens the rigor and clarity of the Perspective. To address this comment, we have added quantitative summary table (Table-1) that directly compares kidney tubuloids with native kidney tissue and PSC-derived organoids. Please kindly note that, the values presented in the manuscript are intended as qualitative, framework-level estimates that synthesize trends reported across multiple studies and current expert consensus, rather than precise experimental benchmarks tied to any single protocol or dataset. Their purpose is to provide conceptual guidance and contextual comparison, not to prescribe fixed methodological thresholds. Please kindly refer to section-2 in our revised version with marked changes.

 

Comment-2: Integrate limitations earlier and more explicitly. Sections 2-4 read at times as overly optimistic, whereas a more critical discussion of current constraints (inter-laboratory variability, incomplete maturation, lack of vascular/immune components, regulatory hurdles) appears mainly in Section 5. Bringing some of these issues forward will provide a more balanced and realistic picture.

 

Response-2:

We sincerely acknowledge the reviewer for this insightful comment, which has helped us further strengthen the depth and clarity of our manuscript. We fully agree that an earlier and more explicit integration of current limitations is essential to provide a balanced and realistic assessment of kidney tubuloid technologies. This point was also raised by Reviewer 2, and in alignment with both reviewers’ recommendations we have carefully revised the manuscript to integrate key limitations earlier as a consistency of flow and more explicitly discussed in section 5. To address the concern of Reviewer 1 and 2, we have revised Sections 2–4 to explicitly and specifically, in Section 5, we now discuss these challenges in a logical and sequential manner including sub section 5.1. Incomplete functional maturation and segmental representation, 5.2. Model complexity, 5. 3. Technical and scalability challenges, and 5.4. Translational and regulatory considerations. We also clearly marked changes in our revised version.

 

Comment-3: Clarify what is established versus speculative. The manuscript nicely covers microfluidics, EVs, gene editing, and multi‑omics, but the maturity of these approaches differs. It would help readers if you distinguish more clearly between: (a) applications already demonstrated in tubuloids (e.g., certain toxicity models), (b) proof‑of‑concept uses (e.g., specific CRISPR disease models), and (c) future perspectives (biobanks, digital twins, bioartificial kidneys).

 

Response-3:

We sincerely thank the reviewer for this insightful comment. We agree that clearly distinguishing between established applications, proof-of-concept studies, and future perspectives is essential to improve clarity and scientific rigor. In response, we have revised the manuscript to explicitly categorize the maturity of tubuloid-based technologies and applications, thereby providing readers with a more transparent and balanced framework.

In response of your recommendation, the following revisions we implemented-

1. Refined language to avoid overstatement
2. Textual clarification throughout the manuscript
3. Addition of a summary table

Please kindly refer to Section (2-4) in our marked changes revised version.

 

Comment-4: Strengthen and streamline the “computational & multi‑omics” and translational sections. The paragraph on multi‑omics/AI and “digital twins” is interesting but quite general. A bit more concrete detail (one or two specific examples or use‑cases) and, conversely, slightly less promotional wording would make this section more convincing. Likewise, a short paragraph outlining the expected regulatory/validation path (what would be needed for clinical or regulatory use of tubuloid platforms) would align better with the “translational potential” emphasis

 

Response-4:

We thank the reviewer for this insightful and constructive comment. We agree that the original version of the manuscript described computational, multi-omics, and digital-twin concepts at a relatively high level and would benefit from greater concreteness, a more critical tone, and clearer translational framing. We have revised these sections accordingly to improve clarity, rigor, and alignment with the stated translational focus. As per your recommendation, the “computational & multi-omics” section has been revised to include specific and realistic examples of current or near-term applications, including integration of single-cell transcriptomics with functional readouts (e.g., transporter activity and injury markers) to stratify nephrotoxic drug responses in patient-derived tubuloids. Please kindly refer to Section- 3.5 in our marked changes revised version.

 

Comment-5: Polish references and language. Some references appear incomplete or inconsistent in format, and a careful check against the journal’s style will be necessary. The English is generally good; a light language edit for minor repetitions and long sentences would further improve readability.

 

Response-5:

We thank the reviewer for this helpful comment. Please accept our apologies for the referencing errors that arose from our EndNote program, as well as for the redundant phrasing and overly complex sentence structures in the manuscript. We have carefully revised the reference list and the manuscript language to improve consistency, clarity, and readability.

The following revisions and solutions implemented:

1. References: Incomplete citations (missing author names, article titles, journal names, volume/issue numbers, page ranges, or DOIs where applicable) have been corrected. Formatting has been standardized across all references to ensure consistency in style, punctuation, and ordering.
2. Language and Style: The manuscript has undergone a thorough language edit to reduce minor repetitions and streamline overly long or complex sentences. Redundant phrases were removed, and sentence structures were simplified where possible to enhance readability without altering scientific meaning. Transitions between sentences and paragraphs were improved to ensure smoother narrative flow.

 

Finally, we believe that the revisions made in response to the Reviewers’1 insightful comments have significantly strengthened the scientific rigor, clarity, and overall coherence of our manuscript. We are grateful to Reviewer-1 for thoughtful and constructive feedback, which has been instrumental in enhancing the quality and impact of our work. We sincerely appreciate the time and expertise dedicated to evaluating our submission and hope that the revised manuscript now satisfactorily addresses all concerns while contributing meaningfully to the scientific community.

 

Sincerely

All co-authors

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Review of the manuscript pharmaceutics-4036363

Translational potential: Kidney tubuloids in precision medicine and regenerative nephrology

By Muhammad Kamal Hossain et al.

In their narrative review, the authors discuss tubular-specific organoids, commonly known as tubuloids, which are derived from adult kidney epithelial cells and represent a key advancement in kidney organoid technologies.

The authors aimed to discuss kidney organoid technologies and briefly summarized their applications in precision medicine, including disease modelling, regenerative strategies, and biobanking for precision testing.

It should be noted that the challenges associated with kidney organoids and kidney tubuloids are currently widely discussed in the literature. Numerous studies address these topics, for example:

• Miyoshi T, Hiratsuka K, Saiz EG, Morizane R. Kidney organoids in translational medicine: Disease modeling and regenerative medicine. Dev Dyn. 2020 Jan;249(1):34-45.
• Schutgens, F., Rookmaaker, M.B., Margaritis, T. et al.Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol 37, 303–313 (2019). (citied in the manuscript)
• Olde Hanhof CJA, Dilmen E, Yousef Yengej FA, Latta F, Ammerlaan CME, Schreurs J, Hooijmaijers L, Jansen J, Rookmaaker MB, Orhon I, Verhaar MC, Hoenderop JG. Differentiated mouse kidney tubuloids as a novel in vitromodel to study collecting duct physiology. Front Cell Dev Biol. 2023 Jan 25;11:1086823. (citied in the manuscript)

Including those recently published in MDPI:

• Yousef Yengej FA, Jansen J, Rookmaaker MB, Verhaar MC, Clevers H. Kidney Organoids and Tubuloids. Cells. 2020 May 26;9(6):1326. doi: 10.3390/cells9061326. (citied in the manuscript)
• Nakanoh H, Tsuji K, Fukushima K, Uchida N, Haraguchi S, Kitamura S, Wada J. Kidney Organoids: Current Advances and Applications. Life. 2025; 15(11):1680. https://doi.org/10.3390/life15111680

 

Against the background of the aforementioned papers, the manuscript under review is somewhat fragmentary in places. The reading raises certain concerns, and in my opinion, the authors should address the following comments before the manuscript can be considered for publication:

1. The issue of methodology - the manuscript does not specify the scientific evidence the authors relied on when preparing their review. I believe that in the section outlining the manuscript's objectives, the criteria and results of the database and literature review, as well as the principles guiding the final selection of the texts included in the manuscript, should be briefly described.
2. I believe the tone of the manuscript clearly shifts toward discussing "Recent engineering innovations for constructing tubuloids Therefore, it may be appropriate to change the title to better reflect the manuscript's main focus. Alternatively, I suggest expanding the content of Chapter 4.
3. The chapter "Applications in precision medicine is quite brief, especially compared to the other studies mentioned above. The description of using kidney tubuloids to model kidney diseases (e.g., acquired kidney injury and fibrosis) is also very concise. In my opinion, given the chapter's title, it would be appropriate to include a table that briefly illustrates and characterizes examples of research utilizing kidney tubuloids in regenerative nephrology and precision medicine. This table could cover areas such as modeling the pathophysiology of kidney diseases, assessing drug nephrotoxicity, and more. The manuscript would also gain educational value by including a figure that collectively illustrates the directions for applying tubuloids.
4. Renal tubuloid technology is also utilized in experimental and preclinical assessments of drug nephrotoxicity and drug screening. I believe these important topics deserve to be discussed in the manuscript as part of precision medicine. Which markers of nephrotoxicity are analyzed besides KIM-1?
5. Chapter "Challenges and considerations for clinical translation” - it would be better to present the limitations and disadvantages of currently used tubuloids in clearly marked subsections and to discuss these topics in that order.

Author Response

Response to Reviewer 2 Comments

 

Reviewer- 2 Comment:

Response:

We sincerely thank Reviewer 2 for the insightful evaluation of our manuscript. We deeply appreciate your time and effort to strengthen our manuscript. In response to your thoughtful suggestions, we have refined the manuscript to further strengthen clarity, coherence, and translational relevance. We trust that these revisions enhance the overall quality and impact of the review. Below, we respond point-by-point and describe the corresponding changes made in the revised version.

 

Comment-1: The issue of methodology - the manuscript does not specify the scientific evidence the authors relied on when preparing their review. I believe that in the section outlining the manuscript's objectives, the criteria and results of the database and literature review, as well as the principles guiding the final selection of the texts included in the manuscript, should be briefly described.

 

Response-1:

We sincerely thank the Reviewer-2 for this thoughtful and constructive comment. We agree that greater methodological transparency will strengthen the rigor and clarity of the Perspective, and that the balance between engineering advances and translational applications required refinement. To address the concern regarding the scientific evidence underlying the review, we have added methodological approach in the Introduction. Please kindly refer to section-1 in our revised version with marked changes.

 

Comment-2: I believe the tone of the manuscript clearly shifts toward discussing "Recent engineering innovations for constructing tubuloids Therefore, it may be appropriate to change the title to better reflect the manuscript's main focus. Alternatively, I suggest expanding the content of Chapter 4.

 

Response-2:

We sincerely acknowledge the reviewer for this insightful comment, which has helped us further strengthen the depth and clarity of our manuscript. We fully agree that a more critical assessment is essential for a balanced and informative review align with our manuscript title.  To address this, we implemented the following changes:

Expanded Section:  2- 4 to more explicitly connect engineering advances (e.g., microfluidics, biomaterials, and bioengineering approaches) with their functional and translational implications in precision medicine and regenerative nephrology. Added clearer transitional statements to ensure that engineering innovations are consistently framed as enabling technologies rather than standalone topics.

Please kindly note, this point was also raised by Reviewer 1, and in alignment with both reviewers’ recommendations we have carefully revised the manuscript.

Please kindly refer to section- (2-4) in our revised version with marked changes.

 

Comment-3: The chapter "Applications in precision medicine is quite brief, especially compared to the other studies mentioned above. The description of using kidney tubuloids to model kidney diseases (e.g., acquired kidney injury and fibrosis) is also very concise. In my opinion, given the chapter's title, it would be appropriate to include a table that briefly illustrates and characterizes examples of research utilizing kidney tubuloids in regenerative nephrology and precision medicine. This table could cover areas such as modeling the pathophysiology of kidney diseases, assessing drug nephrotoxicity, and more. The manuscript would also gain educational value by including a figure that collectively illustrates the directions for applying tubuloids.

 

Response-3:

We sincerely appreciate for this constructive and insightful comment. We agree that the “Applications in precision medicine” section was comparatively brief and that its scope can be expanded to better reflect the breadth and translational relevance of kidney tubuloid applications. To address this concern, we have made the following revisions:

1. Expanded the text of the “Applications in precision medicine” (section-4).
2. Added a new summary table (Table 2).
3. Included new schematic figures illustrating tubuloid applications (Fig. 2) and tubuloid-based drug screening platforms (Fig. 3).

Comment-4: Renal tubuloid technology is also utilized in experimental and preclinical assessments of drug nephrotoxicity and drug screening. I believe these important topics deserve to be discussed in the manuscript as part of precision medicine. Which markers of nephrotoxicity are analyzed besides KIM-1?

 

Response-4:

We sincerely We thank the reviewer for this important and insightful comment. We agree that the application of renal tubuloids in experimental and preclinical drug nephrotoxicity testing and drug screening is a key aspect of precision medicine and warrants more explicit discussion in the manuscript.

In response, we have expanded the section- 4.4 to include a dedicated paragraph and table-2 describing the use of kidney tubuloids for nephrotoxicity assessment and pharmacological screening.

Please kindly refer to section 4.4 and table- 2 in our marked changes revised version.

Comment-5: Chapter "Challenges and considerations for clinical translation” - it would be better to present the limitations and disadvantages of currently used tubuloids in clearly marked subsections and to discuss these topics in that order.

 

Response-5:

We thank the reviewer for this constructive suggestion. We agree that a clearer and more structured presentation of the limitations will improve readability and strengthen the critical perspective of the manuscript. In response, we have substantially revised the chapter “Challenges and considerations for clinical translation” by reorganizing it into clearly defined subsections that systematically address the major limitations of current tubuloid technologies. Specifically, in Section 5, we now discuss the challenges in a logical and sequential manner including sub section 5.1. Incomplete functional maturation and segmental representation, 5.2. Model complexity, 5. 3. Technical and scalability challenges, and 5.4. Translational and regulatory considerations. We also clearly marked changes in our revised version.

Finally, we believe that the revisions made in response to the Reviewers’2 insightful comments have significantly strengthened the scientific rigor, clarity, and overall coherence of our manuscript. We are grateful to Reviewer-2 for thoughtful and constructive feedback, which has been instrumental in enhancing the quality and impact of our work. We sincerely appreciate the time and expertise dedicated to evaluating our submission and hope that the revised manuscript now satisfactorily addresses all concerns while contributing meaningfully to the scientific community.

 

Sincerely

All co-authors

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

In this work kidney tubuloids in precision medicine and regenerative nephrology are described. Authors outline recent advances that position tubuloids as a versatile platform for drug screening, toxicity testing and personalized disease modeling. Also, persistent barriers that impede broader adoption and clinical translation are discussed. The work is of interesting because the study proposes a roadmap for advancing tubuloid technologies toward precision nephrology and their future incorporation into diagnostic, pharmacological and regenerative pipelines. I think that this review may be published after minor revision.

Notes:

1. The introduction should include a summary figure that reflects the essence of this review.
2. The captions in Figure 1 should be increased for clarity. The quality of the drawing should also be improved.
3. How does your review differ from reviews devoted to kidney tubuloids presented in literature? [Yousef Yengej, F. A., Jansen, J., Rookmaaker, M. B., Verhaar, M. C., Clevers, H. (2020). Kidney organoids and tubuloids. Cells, 9(6), 1326; Dilmen, E., Orhon, I., Jansen, J., Hoenderop, J. G. J. (2024). Advancements in kidney organoids and tubuloids to study (dys) function. Trends in Cell Biology, 34(4), 299-311; Nunez-Nescolarde, A. B., Nikolic-Paterson, D. J., Combes, A. N. (2022). Human kidney organoids and tubuloids as models of complex kidney disease. The American journal of pathology, 192(5), 738-749]
4. Are there any limitations to tubuloid technologies in medical therapy? It should be reflected in Conclusions.

Author Response

Response to Reviewer 3 Comments

 

Reviewer- 1 Comment:

Response:

We sincerely thank Reviewer 3 for the insightful evaluation of our manuscript. We deeply appreciate your time and effort to strengthen our manuscript. In response to your thoughtful suggestions, we have refined the manuscript to further strengthen clarity, coherence, and translational relevance. We trust that these revisions enhance the overall quality and impact of the review. Below, we respond point-by-point and describe the corresponding changes made in the revised version.

 

Comment-1: The introduction should include a summary figure that reflects the essence of this review.

 

Response-1:

We sincerely thank for this thoughtful and valuable comment. We fully agree that a summary figure would enhance the clarity and overall impact of the introduction. In response, we have now added a new summary figure (Graphical Abstract) to the manuscript that visually captures the central themes and structure of the review. Please kindly note that for more visual explanation with subsequent section, we also have incorporated 3 more figures (Fig.1, 2 and 3) throughout the manuscript.

 

Comment-2: The captions in Figure 1 should be increased for clarity. The quality of the drawing should also be improved.

 

Response-2:

We sincerely acknowledge the reviewer for this insightful comment, which has helped us further strengthen the clarity of our figure. We appreciate this practical recommendation to improve figure readability. Align with your comment 1 we revised the figure 1.

Comment-3: How does your review differ from reviews devoted to kidney tubuloids presented in literature? [Yousef Yengej, F. A., Jansen, J., Rookmaaker, M. B., Verhaar, M. C., Clevers, H. (2020). Kidney organoids and tubuloids. Cells, 9(6), 1326; Dilmen, E., Orhon, I., Jansen, J., Hoenderop, J. G. J. (2024). Advancements in kidney organoids and tubuloids to study (dys) function. Trends in Cell Biology, 34(4), 299-311; Nunez-Nescolarde, A. B., Nikolic-Paterson, D. J., Combes, A. N. (2022). Human kidney organoids and tubuloids as models of complex kidney disease. The American journal of pathology, 192(5), 738-749]

 

Response-3:

We thank the reviewer for highlighting the importance of distinguishing our contribution. The cited reviews have substantially contributed to the field, and we fully acknowledge their relevance. Our review differs from these prior works in several key aspects. First, our perspective frames tubuloids explicitly through a translational and precision medicine lens, integrates engineering innovations with clinical applicability and links tubuloids to digital health, AI, and multi-omics integration. our review synthesizes recent advances in perfusion systems, microphysiological platforms, and patient-specific disease modeling, integrating evidence published after the earlier reviews. Finally, we highlight current limitations and a forward-looking roadmap, outlining concrete steps needed to move tubuloids toward clinical application.

Comment-4: Are there any limitations to tubuloid technologies in medical therapy? It should be reflected in Conclusions.

 

Response-4:

We sincerely thanks for your insightful suggestions. We fully agree that therapeutic limitations must be clearly acknowledged. Align with the same point raised from Reviewer 1 and 2, we have substantially revised the chapter “Challenges and considerations for clinical translation” by reorganizing it into clearly defined subsections that systematically address the major limitations of current tubuloid technologies. Specifically, in Section 5, we now discuss the challenges in a logical and sequential manner including sub section 5.1. Incomplete functional maturation and segmental representation, 5.2. Model complexity, 5. 3. Technical and scalability challenges, and 5.4. Translational and regulatory considerations. We also clearly marked changes in our revised version.

 

Finally, we believe that the revisions made in response to the Reviewers’3 insightful comments have significantly strengthened the scientific rigor, clarity, and overall coherence of our manuscript. We are grateful to Reviewer-3 for thoughtful and constructive feedback, which has been instrumental in enhancing the quality and impact of our work. We sincerely appreciate the time and expertise dedicated to evaluating our submission and hope that the revised manuscript now satisfactorily addresses all concerns while contributing meaningfully to the scientific community.

 

Sincerely

All co-authors

 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I appreciate the excellent work done on the revisions and thank the authors for their detailed response; however, please ensure the bibliography is carefully reviewed to correct remaining duplicates and formatting inconsistencies before publication.

Author Response

Reviewer 1 Comment:

Comment-1: I appreciate the excellent work done on the revisions and thank the authors for their detailed response; however, please ensure the bibliography is carefully reviewed to correct remaining duplicates and formatting inconsistencies before publication.

 

Response-1:

We sincerely thank the Reviewer-1 for positive evaluation of the revised manuscript and for appreciating the efforts made in addressing the previous comments.

We also acknowledge the Reviewer’s 1, attention to the bibliography. In response, we have thoroughly re-checked the reference list using EndNote and ensured strict compliance with the MDPI/Pharmaceutics journal guidelines (ACS reference style). All remaining duplicate entries have been removed, and formatting inconsistencies have been corrected to ensure accuracy, consistency, and completeness across the bibliography.

We appreciate the reviewer’s valuable suggestion, which has helped further improve the overall quality and presentation of the manuscript.

Please kindly refer to “Reference List” in our revised version with marked changes.

 

Again, we are grateful to Reviewer-1 for thoughtful and constructive feedback, which has been instrumental in enhancing the quality and impact of our work. We sincerely appreciate the time and expertise dedicated to evaluating our revised submission and hope that the revised manuscript now satisfactorily addresses all concerns while contributing meaningfully to the scientific community.

Sincerely,

All co-authors

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Re-Review of the manuscript pharmaceutics-4036363

Translational potential: Kidney tubuloids in precision medicine and regenerative nephrology

By Muhammad Kamal Hossain et al.

 

Thank you for submitting the revised version of the manuscript. The authors have thoroughly redesigned the manuscript, including changes to Figure 1 and the addition of Figures 2 and 3, as well as Tables 1 and 2. These improvements significantly enhance the quality of the manuscript and make it easier to read.

I would also suggest a few minor corrections:

1. In the Introduction, in the section on source selection methodology (specifically, the search period?), it would be helpful to specify who made the final selection of the initially identified articles and the criteria used for this selection (e.g., analysis of titles and abstract content).
2. To improve readability, Table 1 should be presented in landscape orientation in the publication.
3. Line 268 – the paragraph should begin with a capital letter.

TECHNICAL NOTE: The reference list has not yet been prepared in accordance with the guidelines applicable to MDPI journals. However, this will likely be corrected by the editorial team.

Author Response

Response to Reviewer 2 Comments (Round-2)

 

Reviewer- 2 Comment:

Thank you for submitting the revised version of the manuscript. The authors have thoroughly redesigned the manuscript, including changes to Figure 1 and the addition of Figures 2 and 3, as well as Tables 1 and 2. These improvements significantly enhance the quality of the manuscript and make it easier to read.

Response:

We sincerely thank Reviewer 2 for the positive evaluation of the revised manuscript and for acknowledging the improvements made in its structure and presentation.

We are grateful for the Reviewer’s 2 valuable suggestions and constructive guidance, which made it possible for us to thoroughly redesign the manuscript. In response, we revised Figure 1, added new Figures 2 and 3, and incorporated Tables 1 and 2 to improve clarity, organization, and readability. These changes were implemented specifically to address the reviewer’s recommendations and to enhance the overall quality of the manuscript.

We truly appreciate the reviewer’s insightful feedback, which has been instrumental in strengthening the manuscript.

Minor corrections suggested by Reviewer 2

Comment-1: In the Introduction, in the section on source selection methodology (specifically, the search period?), it would be helpful to specify who made the final selection of the initially identified articles and the criteria used for this selection (e.g., analysis of titles and abstract content).

Response-1:

We thank the reviewer for this helpful comment. The Introduction has been revised to clarify the literature search period, article screening process, and selection criteria. We now specify that a structured search covering 2010–2025 was conducted across PubMed, Web of Science, Google Scholar, and Scopus. Articles were independently screened by the authors based on titles and abstracts, and final selection was achieved by consensus, emphasizing methodological rigor, physiological relevance, reproducibility, and translational significance. These revisions improve the transparency of the source selection methodology.

Please kindly refer to “Introduction- Line: 88-95” in our revised version with marked changes.

 

Comment-2: To improve readability, Table 1 should be presented in landscape orientation in the publication.

Response-2:

We thank the reviewer for this helpful suggestion to improve readability. As recommended, Table 1 has been reformatted and is now presented in landscape orientation in the revised manuscript. All corresponding changes have been clearly marked in the revised version for ease of reference.

Please kindly refer to “Page No.- 8” in our revised version with marked changes.

 

Comment-3: Line 268 – the paragraph should begin with a capital letter.

Response-3:

We thank the reviewer for pointing out this typographical oversight. The paragraph at Line 268 (now line 260 in revised version) has been corrected to begin with a capital letter, and the change has been clearly marked in the revised version of the manuscript.

Please kindly refer to “Line-260” in our revised version with marked changes.

 

Comment-4: TECHNICAL NOTE: The reference list has not yet been prepared in accordance with the guidelines applicable to MDPI journals. However, this will likely be corrected by the editorial team.

Response-4:

We acknowledge the Reviewer’s 2, attention to the bibliography. In response, we have thoroughly re-checked the reference list using EndNote and ensured strict compliance with the MDPI/Pharmaceutics journal guidelines (ACS reference style). We appreciate the reviewer’s valuable suggestion, which has helped further improve the overall quality and presentation of the manuscript.

 

Again. we are grateful to Reviewer-2 for thoughtful and constructive feedback, which has been instrumental in enhancing the quality and impact of our work. We sincerely appreciate the time and expertise dedicated to evaluating our submission and hope that the revised manuscript now satisfactorily addresses all concerns while contributing meaningfully to the scientific community.

Sincerely

All co-authors

 

Author Response File: Author Response.pdf