Diabetic kidney disease in northwest Ethiopia: Prevalence and determinants among adults with type 2 diabetes

Workagegnehu Hailu; Tadesse Asmamaw Dejene; Markeshaw Tiruneh; Meseret Derbew Molla; Eshetie Melese Birru; Shitaye Alemu; Tadesse Awoke

doi:10.1371/journal.pone.0343210

Peer Review History

Original SubmissionOctober 11, 2025
17 Nov 2025 Decision Letter - Francesca D'Addio, Editor Dear Dr. Hailu, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== ACADEMIC EDITOR:-->The paper sounds very interesting in addressing an emerging epidemic, the development of DKD, also in Africa. It is well-structured and clear-cut. Although the analysis is limited to a single experience it provides an important information in how DKD is also expanding in non western countries. As a main suggestion to appreciate the relevance of the study, it would be interesting to reinforce the strenghts of the study in the discussion. Why is this study informative despite its limitations? How does it compare to other studies conducted in similar countries? Is it larger? First describing DKD in a specific population? The descriptive nature of the study should be also better clarifies in the text. The Literature cited is quite limited and sometimes not updated. The Authors should follow the Reviewers suggestions to improve this section. Please pay particular attention to Reviewer #1 comments, which may improve the text. ?> ============================== Please submit your revised manuscript by Jan 01 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). 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We notice that your supplementary figures are uploaded with the file type 'Other'. Please amend the file type to 'Supporting Information'. Please ensure that each Supporting Information file has a legend listed in the manuscript after the references list. 6. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Additional Editor Comments: The paper sounds very interesting in addressing an emerging epidemic, the development of DKD, also in Africa. It is well-structured and clear-cut. Although the analysis is limited to a single experience it provides an important information in how DKD is also expanding in non western countries. As a main suggestion to appreciate the relevance of the study, it would be interesting to reinforce the strenghts of the study in the discussion. Why is this study informative despite its limitations? How does it compare to other studies conducted in similar countries? Is it larger? First describing DKD in a specific population? The descriptive nature of the study should be also better clarifies in the text. The Literature cited is quite limited and sometimes not updated. The Authors should follow the Reviewers suggestions to improve this section. Please pay particular attention to Reviewer #1 comments, which may improve the text. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: I Don't Know Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: 1) In the multivariable analysis, rural residence has an AOR < 1 (0.278), suggesting lower odds of DKD; however, the Discussion interprets rural residence as a risk factor. Can the authors confirm the reference category, re-check multivariable model coding and interpretation and correct text accordingly. 2) Since CKD-EPI and albuminuria categories were used, full KDIGO classification (G and A categories) should be reported. It would be good add a table summarizing G-stage and A-stage distributions. 3)Participants were recruited from a tertiary care center and may not reflect the community diabetic population, therefore it is necessary to clarify to what extent the cohort is representative. 4) Multiple statements imply causation, even if this is a cross-sectional study, I suggest to make a revision of the language using “associated with” rather than “predicts” or “leads to” 5) Can the authors add more details about the regression model, clarifying which variables were included and why they were chosen. 6) In the introduction I suggest to reduce the epidemioloy 7) Can the author clarify whether ACR measurement was repeated to confirm presence of albuminuria? 8) Can you clarify whether DKD prevalence differs between urban and rural subgroups? 9) In the discussion can the authors explain the mechanism behind early albuminuria with preserved eGFR? 10) The diabetic drugs in use are insulin, metformin, sulfonylureas which don’t provide diabetic kidney protection, can you make a comment regarding the neuw class of drugs such as SGLT2i and GLP-1RA mentioning the following articles: -AWARE A novel web application to rapidly assess cardiovascular risk in type 2 diabetes mellitus Berra, C., Manfrini, R., Mirani, M., ... Fiorina, P., Folli, F. Acta Diabetologica, 2023, 60(9), pp. 1257–1266 -Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE−2 study Berra, C., Manfrini, R., Bifari, F., ... Cimino, V., Folli, F. Pharmacological Research, 2024, 210, 107517 11) Check the english spelling and change Sulfonureas into Sufonylureas Reviewer #2: The paper is overall well written and structured and give novel information concerning the prevalence of DKD in Ethiopia. To put the paper in a bigger scenario, I suggest including a paragraph in the discussion concerning novel therapeutic approaches to couteract DKD. In particular the authors can consider to cite the following papers: PMID 35908663; PMID 36871895 ****** what does this mean? ). If published, this will include your full peer review and any attached files. 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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. https://doi.org/10.1371/journal.pone.0343210.r001
Revision 1
15 Jan 2026 Author Response Answer to editor and Reviewers comment Editor’s comment The paper sounds very interesting in addressing an emerging epidemic, the development of DKD, also in Africa. It is well-structured and clear-cut. Although the analysis is limited to a single experience it provides an important information in how DKD is also expanding in non western countries. As a main suggestion to appreciate the relevance of the study, it would be interesting to reinforce the strenghts of the study in the discussion. Why is this study informative despite its limitations? How does it compare to other studies conducted in similar countries? Is it larger? First describing DKD in a specific population? The descriptive nature of the study should be also better clarifies in the text. The Literature cited is quite limited and sometimes not updated. The Authors should follow the Reviewers suggestions to improve this section. Please pay particular attention to Reviewer #1 comments, which may improve the text. Response to editor’s comment Thank you for reviewing our manuscript and for your constructive and insightful feedback. We have carefully addressed your comments as well as those of the reviewers. 1. In response to your suggestion to better emphasize the relevance of the study, we have revised the Discussion section by renaming the final subsection from “Limitations” to “Strengths and Limitations” and by explicitly highlighting the strengths of our research. The key strength of our study is that it is based on primary data collected specifically for this investigation, whereas many previous studies from similar settings relied on secondary or registry data. In addition, several prior studies defined DKD solely using eGFR, which primarily captures more advanced disease (CKD stage 3 and above). In contrast, our study employed multiple complementary markers of DKD, including spot urine albumin-to-creatinine ratio (ACR), 24-hour urine protein measurement, and eGFR estimated using both creatinine and cystatin C. This comprehensive approach allowed us to identify early stages of DKD, including albuminuria in patients with preserved eGFR, which is particularly relevant for early detection and prevention strategies in resource limited settings where access to kidney replacement therapy is limited. See “Strengths and Limitation” section 2. Descriptive nature of the study- Thank you for this comment. We would like to clarify that our study is an analytical cross-sectional study with a descriptive component, designed to estimate the prevalence of diabetic kidney disease and to examine factors associated with its presence. 3. Thank you for your comment regarding the literature cited. We have carefully reviewed the reference list and updated it to include more recent and relevant studies on diabetic kidney disease, particularly from low- and middle-income countries. Additional references have been added throughout the manuscript to provide a more comprehensive and current context for our study. Response to Reviewer #1 comment Comment 1: In the multivariable analysis, rural residence has an AOR < 1 (0.278), suggesting lower odds of DKD; however, the Discussion interprets rural residence as a risk factor. Can the authors confirm the reference category, re-check multivariable model coding and interpretation and correct text accordingly. Response: Thank you for this comment. We have re-checked the coding of the multivariable model and confirmed that urban residence is the exposure with an AOR < 1 (AOR = 0.278), indicating a protective effect compared with rural residence (the reference category). The Results and Discussion have been reviewed and are consistent with this interpretation. (See Table 4 and Discussion section) Comment 2: Since CKD-EPI and albuminuria categories were used, full KDIGO classification (G and A categories) should be reported. It would be good add a table summarizing G-stage and A-stage distributions. Response: Thank you for this important suggestion. In our study, the majority of DKD cases were identified based on albuminuria, and the albuminuria categories (A-stages) are presented in Figure 1. In addition, the proportion of DKD diagnosed using different criteria is summarized in Table 3. As shown in Table 3, only 7.4% of participants met the CKD definition based on reduced eGFR (CKD-EPI creatinine, eGFR < 60 mL/min/1.73 m²). We explored presenting the full KDIGO G and A combined staging (e.g., G1A2, G1A3, G2A2, G2A3, G3A1, G3A2, G3A3 etc). However, because the proportion of participants with G3 or higher stages was very small, this resulted in a lengthy table with several cells containing very low frequencies, which we felt would add limited interpretive value. Therefore, we opted to present the data as currently shown. Nevertheless, we are happy to include a table summarizing the full KDIGO G and A staging if the reviewer feels it is necessary. Comment 3: Participants were recruited from a tertiary care center and may not reflect the community diabetic population, therefore it is necessary to clarify to what extent the cohort is representative. Response: Thank you for this valid comment. We have addressed this issue by adding the following statement to the Limitations section to clarify the representativeness of the study population: “The study was conducted in a tertiary care hospital, where patients with more complex or advanced type 2 diabetes mellitus are more likely to seek follow-up care. As a result, the findings may not be fully generalizable to diabetic patients managed in primary or community-based settings.” Comment 4: Multiple statements imply causation, even if this is a cross-sectional study, I suggest to make a revision of the language using “associated with” rather than “predicts” or “leads to” Response: Thank you for this important comment. We have revised the manuscript to remove causal language and replaced by “associated with” Comment 5: Can the authors add more details about the regression model, clarifying which variables were included and why they were chosen. Response: Thank you for this comment. We have clarified the regression modeling approach in the Methods section (under “statistical analysis”) and Results section (under “Factors associated with DKD in patients with T2DM.” Variables with a p-value ≤ 0.20 in the bivariate analysis—namely place of residence, presence of comorbidities, blood pressure control status, glycemic control status, and duration of diabetes—were selected for inclusion in the multivariable logistic regression model. Comment 6: In the introduction I suggest to reduce the epidemiology Response: Thank you for this suggestion. We have revised the Introduction to reduce the epidemiology content and improve focus and conciseness. Comment 7: Can the author clarify whether ACR measurement was repeated to confirm presence of albuminuria? Response: Thank you for this important question. The spot urine albumin-to-creatinine ratio (ACR) measurement was not repeated. However, all participants additionally underwent quantitative urine protein assessment using a 24-hour urine protein excretion test, which was used as the reference (gold standard) to confirm the presence of albuminuria and to define DKD in this study. To clarify this we put the following in the methods (under blood and urine collection and processing section) “A first-morning midstream urine sample was collected from all participants for measurement of the spot urine albumin-to-creatinine ratio (ACR). The ACR measurement was performed once and was not repeated. In addition, all participants underwent quantitative assessment of albuminuria using a 24-hour urine protein excretion test” Comment 8: Can you clarify whether DKD prevalence differs between urban and rural subgroups? Response: Thank you for this question. DKD prevalence was 35.3% in urban participants (65/184) and 55.0% in rural participants (11/20). A chi-square test showed no statistically significant difference between the groups (χ² = 2.20, p = 0.14). In the multivariable analysis, urban residence was associated with lower odds of DKD (AOR = 0.278, Table 4), as discussed in the manuscript. Comment 9: In the discussion can the authors explain the mechanism behind early albuminuria with preserved eGFR? Response: Thank you for this valid comment. We have addressed this by adding a dedicated paragraph in the Discussion section explaining the pathophysiological mechanisms underlying the development of albuminuria in the presence of preserved eGFR, within the section where albuminuria is discussed. We have added the following paragraph with respective references “In DKD, albuminuria often develops before a decline in estimated glomerular filtration rate (eGFR) because the initial pathogenic changes in the diabetic kidney primarily affect the glomerular filtration barrier rather than overall filtration function. Chronic hyperglycemia induces both structural and functional alterations in the glomerular capillary wall, including thickening of the basement membrane, podocyte injury or loss, widening of foot processes, and endothelial dysfunction with reduced nitric oxide production and decreased negative charge of the basement membrane. Proximal tubular dysfunction may also impair reabsorption of filtered albumin, contributing to albuminuria even when eGFR is still preserved. Hemodynamic changes, such as glomerular hyperfiltration, hyperperfusion, and elevated intraglomerular pressure, further promote early albumin leakage”. Comment 10: The diabetic drugs in use are insulin, metformin, sulfonylureas which don’t provide diabetic kidney protection, can you make a comment regarding the neuw class of drugs such as SGLT2i and GLP-1RA mentioning the following articles: -AWARE A novel web application to rapidly assess cardiovascular risk in type 2 diabetes mellitus Berra, C., Manfrini, R., Mirani, M., ... Fiorina, P., Folli, F. Acta Diabetologica, 2023, 60(9), pp. 1257–1266 -Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE−2 study Berra, C., Manfrini, R., Bifari, F., ... Cimino, V., Folli, F. Pharmacological Research, 2024, 210, 107517 Response: Thank you for this valuable suggestion. We have added a paragraph in the Discussion highlighting the potential of novel therapeutic approaches, including SGLT2 inhibitors and GLP-1 receptor agonists, in slowing the progression of diabetic kidney disease. We also emphasize the importance of improving access to and appropriate use of these effective therapies in resource-limited settings like Ethiopia. We have included citation related to this. Comment 11: Check the english spelling and change Sulfonureas into Sufonylureas Response: Thank you for noting this. We have corrected the spelling accordingly Response to Reviewer #2 Comment 1: The paper is overall well written and structured and give novel information concerning the prevalence of DKD in Ethiopia. Response: Thank you for your positive comment and appreciation of our work Comment 2: To put the paper in a bigger scenario, I suggest including a paragraph in the discussion concerning novel therapeutic approaches to couteract DKD. In particular the authors can consider to cite the following papers: PMID 35908663; PMID 36871895 Response: Thank you for this valuable suggestion. We have added a paragraph in the Discussion highlighting the potential of novel therapeutic approaches, including SGLT2 inhibitors and GLP-1 receptor agonists, in slowing the progression of diabetic kidney disease. We also emphasize the importance of improving access to and appropriate use of these effective therapies in resource-limited settings like Ethiopia. The suggested references have been cited accordingly Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0343210.r002
4 Feb 2026 Decision Letter - Francesca D'Addio, Editor <p>Diabetic Kidney Disease in Northwest Ethiopia: Prevalence and Determinants Among Adults with Type 2 Diabetes PONE-D-25-53996R1 Dear Dr. Hailu, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Francesca D'Addio, MD, PhD Academic Editor PLOS One Additional Editor Comments (optional): By responding for the most part to the main comments raised by the Reviewers, the paper has been significantly improved and it is now suitable for publication. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: The authors has adequately addressed the comments and now the article has reached a good level and It is now acceptable for publication, it is presented in a n intelligible fashion and written in standard english. Reviewer #2: The authors addressed all reviewers' comments. I just would like to highlight that the bibliography han not been updated as compared to the previous version. ****** what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0343210.r003
Formally Accepted
Acceptance Letter - Francesca D'Addio, Editor PONE-D-25-53996R1 PLOS One Dear Dr. Hailu, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Prof. Francesca D'Addio Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0343210.r004

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