Albuminuria Categories at Screening and Associated Clinical Factors in Adults with Type 2 Diabetes, Preserved eGFR, and No Prior Diagnosis of Diabetic Kidney Disease: An Exploratory Single-Center Cross-Sectional Study in Western Mexico

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript addresses a clinically relevant issue: the identification of albuminuria in adults with type 2 diabetes mellitus without a previous diagnosis of diabetic kidney disease. The study is of potential interest because it provides regional data from western Mexico, a setting that is relatively underrepresented in the literature. The manuscript is generally clearly written, the objectives are understandable, and the authors appropriately present the study as exploratory and hypothesis-generating.

However, several points require clarification and revision before the manuscript can be considered suitable for publication.

1. Study design and interpretation

The cross-sectional and single-center nature of the study should be emphasized more consistently throughout the manuscript. The current results can describe the frequency of albuminuria categories at screening, but they cannot establish temporality, causality, progression, regression, or persistent diabetic kidney disease.

The authors should avoid any wording that may imply that the observed albuminuria definitively represents established diabetic kidney disease. Since albuminuria was assessed using a single first-morning uACR measurement, the results should be described as “albuminuria detected at screening” or “albuminuria categories based on a single uACR measurement”, rather than as confirmed persistent kidney disease.

2. Single uACR measurement

The use of only one uACR measurement is a major limitation. Albuminuria has considerable biological variability and should generally be confirmed by repeated measurements before persistent albuminuria or diabetic kidney disease is diagnosed.

The authors already mention this limitation, but its implications should be strengthened in the Discussion and Conclusions. In particular, the manuscript should clearly state that the study identifies patients with abnormal uACR at one screening assessment, not patients with confirmed persistent albuminuria.

3. Interpretation of A3 albuminuria

The presence of severely increased albuminuria in 10.1% of patients is clinically important and requires deeper discussion. Patients in the A3 category had very high uACR values, and this finding should not be treated simply as part of an “early screening” framework.

The authors should discuss whether alternative or additional causes of severe albuminuria were considered. Although patients with known kidney disease, urinary tract infection, fever, recent NSAID use, and other transient conditions were excluded, severe albuminuria may still reflect unrecognized kidney disease or non-diabetic renal pathology. This is especially relevant because the study excluded patients with a previous diagnosis of diabetic kidney disease, but did not confirm the persistence or etiology of albuminuria.

4. Pharmacological treatment data

The absence of systematic information on antidiabetic and cardiorenal medications is one of the most important limitations of the study. The authors state that data on RAAS inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, insulin, and other antihyperglycemic therapies were not systematically available.

This limitation should be given greater weight. These therapies may influence albuminuria, eGFR, glycemic control, blood pressure, and cardiorenal risk. In particular, ACE inhibitors/ARBs and SGLT2 inhibitors may directly affect albuminuria. Therefore, the lack of medication data limits the interpretation of the associations between HbA1c, eGFR, diabetes duration, and albuminuria category.

The authors should explicitly state that residual confounding by treatment cannot be excluded.

5. Glycemic control and generalizability

The cohort had very poor glycemic control, with a median HbA1c of 11.2% and a median fasting glucose of 280 mg/dL. This should be discussed more clearly as a major characteristic of the study population.

The high frequency of albuminuria may partly reflect the inclusion of patients with markedly uncontrolled diabetes. Therefore, the findings should not be generalized to all adults with type 2 diabetes or to populations with better glycemic control. The authors should make clear that the results apply primarily to this selected regional hospital cohort.

6. Statistical model and sample size

The multivariable ordinal logistic regression is reasonable as an exploratory analysis, but the model should be interpreted very cautiously because the sample size is modest and the A3 group includes only 12 patients.

The authors should avoid overemphasizing the independence or robustness of the associations. The Results and Discussion should consistently describe the regression findings as exploratory. It would also be helpful to report whether model stability was assessed, or at least to acknowledge that the limited number of patients in the A3 category may reduce the reliability of the ordinal model.

7. Binary outcome A2/A3 versus A1

The secondary binary analysis combines A2 and A3 albuminuria. This is clinically understandable, but A2 and A3 represent different degrees of renal risk. The authors should acknowledge that grouping A2 and A3 together may obscure clinically relevant differences, especially given the very high uACR values observed in the A3 group.

8. Hypertension and blood pressure

The lack of association between hypertension and albuminuria should be interpreted cautiously. This may reflect the modest sample size, limited statistical power, treatment effects, incomplete characterization of antihypertensive therapy, or misclassification of hypertension status.

The authors should avoid presenting this as evidence that hypertension is not clinically relevant in this population.

9. Conclusions

The conclusions should be slightly softened. The manuscript can reasonably conclude that systematic uACR screening may identify previously unrecognized albuminuria among patients with type 2 diabetes and preserved eGFR in this regional setting.

However, the conclusions should not imply confirmed diabetic kidney disease, persistent albuminuria, or causal relationships. The need for repeated uACR measurements, longitudinal follow-up, medication data, and larger multicenter cohorts should be emphasized.

10. Overall recommendation to authors

The manuscript has potential value as a regional exploratory study, particularly because it highlights under-recognition of albuminuria in patients with type 2 diabetes and preserved eGFR. Nevertheless, the interpretation should be more cautious, and the limitations related to single uACR measurement, missing medication data, severe A3 albuminuria, poor glycemic control, and model stability should be addressed more explicitly.

If these revisions are made, the manuscript would provide a clearer and more balanced contribution to the literature on albuminuria screening in type 2 diabetes.

Author Response

Study design and interpretation

1. The cross-sectional and single-center nature of the study should be emphasized more consistently throughout the manuscript. The current results can describe the frequency of albuminuria categories at screening, but they cannot establish temporality, causality, progression, regression, or persistent diabetic kidney disease. The authors should avoid any wording that may imply that the observed albuminuria definitively represents established diabetic kidney disease. Since albuminuria was assessed using a single first-morning uACR measurement, the results should be described as “albuminuria detected at screening” or “albuminuria categories based on a single uACR measurement”, rather than as confirmed persistent kidney disease.
   1. Response: We thank the reviewer for this important observation. We agree that the single-center cross-sectional design and the use of one first-morning uACR measurement require more precise terminology. We revised the title and Abstract and standardized the manuscript to describe “screen-detected albuminuria” or “uACR categories at a single screening assessment.” The revised text explicitly states that the study cannot establish persistent albuminuria, diabetic kidney disease, temporality, causality, progression, or regression.

Single uACR measurement

2. The use of only one uACR measurement is a major limitation. Albuminuria has considerable biological variability and should generally be confirmed by repeated measurements before persistent albuminuria or diabetic kidney disease is diagnosed. The authors already mention this limitation, but its implications should be strengthened in the Discussion and Conclusions. In particular, the manuscript should clearly state that the study identifies patients with abnormal uACR at one screening assessment, not patients with confirmed persistent albuminuria.
   1. Response: We agree. The Methods and Results now state explicitly that albuminuria classification was based on one first-morning uACR measurement. The Discussion and Conclusions explain that the study identifies abnormal uACR at one screening assessment and cannot confirm persistent albuminuria or diabetic kidney disease. Repeated uACR measurements are identified as necessary for confirmation.

 

Interpretation of A3 albuminuria

3. The presence of severely increased albuminuria in 10.1% of patients is clinically important and requires deeper discussion. Patients in the A3 category had very high uACR values, and this finding should not be treated simply as part of an “early screening” framework. The authors should discuss whether alternative or additional causes of severe albuminuria were considered. Although patients with known kidney disease, urinary tract infection, fever, recent NSAID use, and other transient conditions were excluded, severe albuminuria may still reflect unrecognized kidney disease or non-diabetic renal pathology. This is especially relevant because the study excluded patients with a previous diagnosis of diabetic kidney disease, but did not confirm the persistence or etiology of albuminuria.
   1. Response: We thank the reviewer for this important observation. We expanded the Discussion to address the clinical significance of A3 albuminuria separately. The revised text reports the markedly elevated uACR values in A3, acknowledges that severe albuminuria may reflect previously unrecognized diabetic kidney disease, non-diabetic renal disease, or other secondary or transient causes, and clarifies that neither persistence nor etiology could be established from one screening measurement. The Discussion was rewritten in full to integrate these points without repetition.

Pharmacological treatment data

4. The absence of systematic information on antidiabetic and cardiorenal medications is one of the most important limitations of the study. The authors state that data on RAAS inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, insulin, and other antihyperglycemic therapies were not systematically available. This limitation should be given greater weight. These therapies may influence albuminuria, eGFR, glycemic control, blood pressure, and cardiorenal risk. In particular, ACE inhibitors/ARBs and SGLT2 inhibitors may directly affect albuminuria. Therefore, the lack of medication data limits the interpretation of the associations between HbA1c, eGFR, diabetes duration, and albuminuria category. The authors should explicitly state that residual confounding by treatment cannot be excluded.
   1. Response: We agree that the absence of systematic medication data is a major limitation. The revised Methods clarify that clinical information was abstracted from medical records rather than obtained through a standardized medication interview. The revised Discussion gives this limitation greater weight and explicitly states that residual confounding by antihyperglycemic, renoprotective, and antihypertensive treatment cannot be excluded.

Glycemic control and generalizability

5. The cohort had very poor glycemic control, with a median HbA1c of 11.2% and a median fasting glucose of 280 mg/dL. This should be discussed more clearly as a major characteristic of the study population.
   11. Response: We agree. The revised Discussion identifies the median HbA1c of 11.2% and fasting glucose of 280 mg/dL as a major characteristic of the cohort. It explains that markedly poor glycemic control may partly account for the high frequency of screen-detected albuminuria and must be considered when interpreting the observed associations.
6. The high frequency of albuminuria may partly reflect the inclusion of patients with markedly uncontrolled diabetes. Therefore, the findings should not be generalized to all adults with type 2 diabetes or to populations with better glycemic control. The authors should make clear that the results apply primarily to this selected regional hospital cohort.
   1. Response: We agree. The revised Discussion states that the findings apply primarily to this selected regional hospital cohort and should not be generalized directly to all adults with T2DM, the broader Mexican population, or populations with better glycemic control. The manuscript no longer presents the observed frequency as a population-based prevalence estimate.

 

Statistical model and sample size

7. The multivariable ordinal logistic regression is reasonable as an exploratory analysis, but the model should be interpreted very cautiously because the sample size is modest and the A3 group includes only 12 patients. The authors should avoid overemphasizing the independence or robustness of the associations. The Results and Discussion should consistently describe the regression findings as exploratory. It would also be helpful to report whether model stability was assessed, or at least to acknowledge that the limited number of patients in the A3 category may reduce the reliability of the ordinal model.
   3. Response: We thank the reviewer for this important observation. We consistently describe both regression models as exploratory and hypothesis-generating. The Statistical Analysis now reports the six prespecified covariates, the proportional odds assessment, the absence of a formal multivariable sample-size calculation or resampling-based internal validation, and the risk of imprecision and overfitting with only 12 participants in A3. The Results avoid the terms “independent predictor” and “robust association,” and Table 5 has been simplified and relabeled accordingly.

 

Binary outcome A2/A3 versus A1

8. The secondary binary analysis combines A2 and A3 albuminuria. This is clinically understandable, but A2 and A3 represent different degrees of renal risk. The authors should acknowledge that grouping A2 and A3 together may obscure clinically relevant differences, especially given the very high uACR values observed in the A3 group.
   3. Response: We agree. The secondary binary model is now described only as a complementary exploratory analysis. The Methods and Discussion explicitly acknowledge that combining A2 and A3 may obscure clinically important differences and does not imply equivalent renal or cardiovascular risk, particularly given the very high uACR values in A3.

Hypertension and blood pressure

9. The lack of association between hypertension and albuminuria should be interpreted cautiously. This may reflect the modest sample size, limited statistical power, treatment effects, incomplete characterization of antihypertensive therapy, or misclassification of hypertension status. The authors should avoid presenting this as evidence that hypertension is not clinically relevant in this population.
   1. Response: We agree. The revised Discussion states that the absence of an observed association with hypertension should not be interpreted as evidence that hypertension is clinically unimportant. The text now considers modest sample size, limited power, treatment effects, incomplete antihypertensive data, and possible misclassification as explanations for the null finding.

Conclusions

10. The conclusions should be slightly softened. The manuscript can reasonably conclude that systematic uACR screening may identify previously unrecognized albuminuria among patients with type 2 diabetes and preserved eGFR in this regional setting. However, the conclusions should not imply confirmed diabetic kidney disease, persistent albuminuria, or causal relationships. The need for repeated uACR measurements, longitudinal follow-up, medication data, and larger multicenter cohorts should be emphasized.
    1. Response: We agree and have softened the Conclusions. The revised section is limited to the finding that a single screening uACR assessment identified previously unrecognized elevated uACR in this selected regional cohort. It explicitly avoids implying persistent albuminuria, confirmed diabetic kidney disease, or causal relationships and emphasizes repeated uACR measurements, medication data, longitudinal follow-up, and larger multicenter cohorts.

Overall recommendation to authors

11. The manuscript has potential value as a regional exploratory study, particularly because it highlights under-recognition of albuminuria in patients with type 2 diabetes and preserved eGFR. Nevertheless, the interpretation should be more cautious, and the limitations related to single uACR measurement, missing medication data, severe A3 albuminuria, poor glycemic control, and model stability should be addressed more explicitly. If these revisions are made, the manuscript would provide a clearer and more balanced contribution to the literature on albuminuria screening in type 2 diabetes.
    1. Response: We thank the reviewer for the careful and constructive assessment. The revised manuscript now consistently frames the study as a regional exploratory screening analysis. It addresses the single uACR measurement, severe A3 albuminuria, markedly poor glycemic control, missing medication data, binary grouping of A2/A3, and limited model stability. The interpretation has been made more cautious throughout.

Reviewer 2 Report

Comments and Suggestions for Authors

I thank the Editor for having involved me in the review process of the manuscript entitled “Albuminuria categories and associated clinical factors in adults with type 2 diabetes mellitus without previously diagnosed diabetic kidney disease: an exploratory cross sectional study in western Mexico”.

The study is a cross sectional one involving a limited number of type 2 diabetic individuals. This study investigated the prevalence and clinical risk factors of albuminuria (excess protein in the urine, indicating kidney damage) among adults with type 2 diabetes (T2DM) in western Mexico who had no prior diagnosis of diabetic kidney disease. Despite having no previous kidney disease diagnosis, nearly 44% of the participants in this 119-patient cohort had elevated albuminuria. The overall cohort also showed very poor glycemic control, with a median HbA1c of 11.2%. Using multivariable regression, the researchers identified three major clinical metrics independently linked to higher stages of albuminuria:

1) every 5 additional years with diabetes increased the odds of being in a higher albuminuria category by 51% (OR 1.51);

2) each 1% increase in HbA1c increased the odds by 18% (OR 1.18);

3) every 10 mL/min/1.73 m² drop in estimated glomerular filtration rate increased the risk of higher albuminuria (OR 0.69).

These findings highlight a high rate of undetected kidney damage in Mexican T2DM patients. The study strongly supports the integration of systematic, early screening programs (like simple urine albumin-to-creatinine ratio tests) to catch kidney decline before it becomes irreversible.

My major criticism is about the main message that it is not a novelty, moreover I think there are some problems with methodology.

Abstract: clinical characteristics of the populations enrolled in this study are missing (i.e. age).

Introduction: this section does not explain the reason for this study.

Methods: the setting where the patients were enrolled is not clear; it should be reported and well explained as well as the volume of work conducted in the selected setting. The sentence “The study included adults with a known diagnosis of type 2 diabetes mellitus 100 (T2DM) who were receiving medical care at the Hospital Regional de Cocula, a regional 101 hospital in western Mexico, between September 2022 and August 2023” is not sufficient.

I hardly understand the emphasis on urinary tract infections, the latter is a transitory event and patients could be enrolled after treatment.

The age of the population is too wide (20-80 years). Authors in the introduction stated “Albuminuria, assessed through the urinary albumin-to-creatinine ratio (uACR), is a clinically accessible marker of kidney damage and cardiorenal risk”, therefore albuminuria could be used to prevent clinical events. It could be interesting to discuss the value of albuminuria in young people, adults and older adults, the latter eventually could have suffered a major cardiovascular event. However, authors did not consider previous major cardiovascular events in this study.   

There are some problems in evaluating glomerular filtration rate in elderly by using CKD-EPI.

Authors stated: “Antihyperglycemic drug classes, renin–angiotensin–aldosterone system inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and insulin use were not systematically available in the original database and were therefore not included as covariates in the statistical models”. This sentence suggests that authors did not ask the patients about their treatment.

Finally, albuminuria was used for patients’ classification and at the same time it is considered the outcome of the study. It sounds strange.

Author Response

1. My major criticism is about the main message that it is not a novelty, moreover I think there are some problems with methodology.
   1. Response: We appreciate the reviewer’s direct assessment. We agree that the established associations between albuminuria, diabetes duration, glycemic control, and eGFR are not mechanistically novel. The revised manuscript presents its contribution as regional and contextual: it documents screen-detected uACR categories in an understudied Mexican hospital-based cohort with preserved eGFR and no previous diagnosis of diabetic kidney disease. The Introduction was rewritten to state this rationale clearly and to avoid overstating novelty.
2. Abstract: clinical characteristics of the populations enrolled in this study are missing (i.e. age).
   1. Response: We agree. The revised Abstract reports the cohort size and mean age, as well as the preserved eGFR criterion, albuminuria distribution, median uACR, HbA1c, and fasting glucose. These additions provide the principal clinical characteristics needed to interpret the findings.
3. Introduction: this section does not explain the reason for this study.
   1. Response: We agree. The revised Introduction now explains that Mexican albuminuria estimates are heterogeneous and that local data are limited for regional hospital populations with preserved eGFR and no previous diagnosis of diabetic kidney disease. The study rationale and contextual contribution are stated immediately before the objective.
4. Methods: the setting where the patients were enrolled is not clear; it should be reported and well explained as well as the volume of work conducted in the selected setting. The sentence “The study included adults with a known diagnosis of type 2 diabetes mellitus (T2DM) who were receiving medical care at the Hospital Regional de Cocula, a regional 101 hospital in western Mexico, between September 2022 and August 2023” is not sufficient.
   1. Response: We thank the reviewer. The revised Methods clarify the hospital setting, outpatient recruitment, the inclusion of patients attending routine follow-up or a first-time evaluation, and the exclusion of hospitalized patients and patients presenting with acute intercurrent illness. The total number of T2DM consultations, screened patients, and non-enrolled patients was not reliably captured; therefore, we explicitly state this limitation rather than provide an unsupported service-volume estimate.
5. I hardly understand the emphasis on urinary tract infections, the latter is a transitory event and patients could be enrolled after treatment.
   1. Response: We agree that urinary tract infection is a transient condition. The revised Methods specify that only active or clinically suspected urinary tract infection at enrollment was an exclusion criterion because it could transiently affect uACR. Potentially eligible patients could be reconsidered after clinical resolution. The manuscript no longer implies permanent exclusion because of a previous treated infection.
6. The age of the population is too wide (20-80 years). Authors in the introduction stated “Albuminuria, assessed through the urinary albumin-to-creatinine ratio (uACR), is a clinically accessible marker of kidney damage and cardiorenal risk”, therefore albuminuria could be used to prevent clinical events. It could be interesting to discuss the value of albuminuria in young people, adults and older adults, the latter eventually could have suffered a major cardiovascular event. However, authors did not consider previous major cardiovascular events in this study.
   1. Response: We appreciate the observation. The study was not designed to evaluate uACR as a predictor of cardiovascular events or to perform age-stratified analyses. The included cohort was concentrated around middle age (median 53 years; IQR 45–62), and the modest sample size would make separate analyses of young, middle-aged, and older adults unreliable. The revised limitations state that age-stratified analyses were not prespecified or adequately powered and that previous major cardiovascular events were not systematically available.
7. There are some problems in evaluating glomerular filtration rate in elderly by using CKD-EPI.
   1. Response: We thank the reviewer. The CKD-EPI equation was applied to adult participants according to the prespecified study protocol. The manuscript does not make age-specific claims, and the cohort median age was 53 years. Because the exact equation version and an independent validation of eGFR in older participants were not documented in the analytical source, we did not add unsupported methodological detail. The revised limitations acknowledge uncertainty in eGFR estimates at age extremes and the absence of age-stratified validation.
8. Authors stated: “Antihyperglycemic drug classes, renin–angiotensin–aldosterone system inhibitors, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and insulin use were not systematically available in the original database and were therefore not included as covariates in the statistical models”. This sentence suggests that authors did not ask the patients about their treatment.
   1. Response: We agree that the original wording could imply that treatment history was not sought. The revised Methods clarify that medical history and concomitant medications were abstracted from clinical records rather than obtained through a standardized medication interview. Medication information was reviewed when available, but complete class-level data were not consistently documented and therefore could not be included as covariates.
9. Finally, albuminuria was used for patients’ classification and at the same time it is considered the outcome of the study. It sounds strange.

Response: We thank the reviewer for allowing us to clarify this point. uACR category was the primary outcome, not both a predictor and an outcome. A1, A2, and A3 are ordered levels used to define that outcome for descriptive comparisons and exploratory ordinal regression. The secondary binary outcome combined A2/A3 versus A1. The revised Outcomes section now states this explicitly.

Reviewer 3 Report

Comments and Suggestions for Authors

In this study, Miranda-Martínez ML and colleagues address an important clinical question by evaluating the prevalence and determinants of albuminuria in patients with type 2 diabetes mellitus (T2DM) without previously diagnosed diabetic kidney disease in a Mexican cohort, a population for which data remain limited. The findings, particularly the associations with diabetes duration, glycemic control, and renal function, are clinically relevant and consistent with existing evidence.

Major points:

1. The authors state that the quantitative variables exhibited a non-normal distribution; however, the method used to assess normality is not specified. Please clarify which statistical test was applied to evaluate the distribution of the data
2. The manuscript would benefit from the inclusion of a graphical abstract that visually summarizes the main experimental design.
3. The results of the correlation analysis are mentioned in the text but are not presented in any figures or tables. Please provide the corresponding data to support these statements.
4. The sample size is small, especially for the A3 group (n = 12). This makes the ordinal and binary regression models unstable and raises the chance of overfitting. The authors should explain the complexity of the models, recognize the limited statistical power, and think about whether the regression results are well-supported.
5. Table formatting should be better for readability. Several tables look crowded and are hard to understand. In particular, Table 3 and Table 4 would benefit from cleaner alignment and a simpler layout.

Minor comments

1. Define all abbreviations at their first mention in the main text and ensure consistency across tables and legends (e.g., HbA1c). Once an abbreviation has been defined, it does not need to be repeated; only the abbreviation should be used thereafter.
2. Some reference formatting appears inconsistent and should be carefully corrected (e.g., “Diab Vasc Dis Res. 2021 Nov-Dec;18(6):14791641211058856” and “Diabetes ObesMetab 2020; 22: 3–15.”)

Weakness

The main novelty of this study lies in its regional assessment of albuminuria among Mexican adults with type 2 diabetes mellitus (T2DM) without previously diagnosed diabetic kidney disease, providing local evidence from an understudied clinical setting rather than introducing novel mechanistic insights. The associations between longer diabetes duration, poorer glycemic control, lower estimated glomerular filtration rate (eGFR), and albuminuria are already well established.

Author Response

Major points

1. The authors state that the quantitative variables exhibited a non-normal distribution; however, the method used to assess normality is not specified. Please clarify which statistical test was applied to evaluate the distribution of the data
   1. Response: We thank the reviewer for identifying this omission. The revised Statistical Analysis states that distributional normality was assessed using the Shapiro–Wilk test. Because several variables were non-normally distributed, quantitative results are reported as median and interquartile range and nonparametric methods were used as appropriate.
2. The manuscript would benefit from the inclusion of a graphical abstract that visually summarizes the main experimental design.
   1. Response: We appreciate this suggestion. A graphical abstract summarizing the single-center cross-sectional design, outpatient cohort, single first-morning uACR classification, exploratory statistical approach, principal findings, and requirement for repeated uACR confirmation was prepared for submission as a separate graphical file.
3. The results of the correlation analysis are mentioned in the text but are not presented in any figures or tables. Please provide the corresponding data to support these statements.
   5. Response: We agree that the complete correlation results should be shown. The revised Results include a dedicated Table 4 reporting Spearman coefficients and p values for T2DM duration, HbA1c, and eGFR, and the narrative now refers directly to that table. The former regression table is renumbered as Table 5.
4. The sample size is small, especially for the A3 group (n = 12). This makes the ordinal and binary regression models unstable and raises the chance of overfitting. The authors should explain the complexity of the models, recognize the limited statistical power, and think about whether the regression results are well-supported.
   1. Response: We agree. The revised manuscript explains the six-covariate model structure, the clinical basis for covariate selection, the small A3 subgroup, the absence of formal internal validation, and the resulting risk of imprecision and overfitting. All regression findings are described as exploratory and hypothesis-generating and require validation in larger cohorts.
5. Table formatting should be better for readability. Several tables look crowded and are hard to understand. In particular, Table 3 and Table 4 would benefit from cleaner alignment and a simpler layout.
   7. Response: We thank the reviewer. The tables were reformatted to remove tracked-change duplication, simplify headings, align numerical values, standardize decimal precision, and place explanatory information in concise legends. Tables 1–3 are replaced below. The final correlation table was inserted under Comment 3, and the final regression table was inserted under Reviewer 1, Comment 7.

 

Minor comments

6. Define all abbreviations at their first mention in the main text and ensure consistency across tables and legends (e.g., HbA1c). Once an abbreviation has been defined, it does not need to be repeated; only the abbreviation should be used thereafter.
   1. Response: We agree. Abbreviations were reviewed throughout the Abstract, main text, tables, and legends so that each term is defined at first use and used consistently thereafter. The abbreviations list was also simplified and standardized.
7. Some reference formatting appears inconsistent and should be carefully corrected (e.g., “Diab Vasc Dis Res. 2021 Nov-Dec;18(6):14791641211058856” and “Diabetes ObesMetab 2020; 22: 3–15.”)
   1. Response: We thank the reviewer. The complete reference list was standardized for author separators, journal abbreviations, capitalization, punctuation, spacing, volume, page range, and article-number presentation. Duplicate wording and merged journal names were removed without changing the order of the references.

 

Weakness

8. The main novelty of this study lies in its regional assessment of albuminuria among Mexican adults with type 2 diabetes mellitus (T2DM) without previously diagnosed diabetic kidney disease, providing local evidence from an understudied clinical setting rather than introducing novel mechanistic insights. The associations between longer diabetes duration, poorer glycemic control, lower estimated glomerular filtration rate (eGFR), and albuminuria are already well established.

Response: We agree. The revised Introduction and Discussion explicitly state that the study’s contribution is regional and contextual rather than mechanistic. The manuscript no longer presents the associations with diabetes duration, glycemic control, or eGFR as novel discoveries; instead, it evaluates these established relationships in an understudied Mexican hospital-based screening cohort.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have adequately addressed the main scientific concerns raised in the previous review round. The revised manuscript is now more appropriately framed as an exploratory study of screen-detected albuminuria, and the limitations related to the single uACR measurement, missing medication data, A3 albuminuria, and model stability are clearly acknowledged.

I have no further scientific concerns and recommend acceptance.

Reviewer 2 Report

Comments and Suggestions for Authors

I thank the Editor for the opportunity to evaluate the revised version of the manuscript entitled “Screen-detected albuminuria categories and associated clinical factors in adults with type 2 diabetes, preserved eGFR, and no previous diagnosis of diabetic kidney disease: an exploratory single-center cross-sectional study in western Mexico”. The authors have performed a great job, the manuscript has greatly improved and now their message is clear. The authors have acknowledged all my concerns and I do not have any more observations. I really appreciate the clinical message contained in the new version of the manuscript, a simple and cheap urinary examination reveals long term metabolic derangement due to type 2 diabetes mellitus independently from diabetic treatment prescribed and this message could be even more important in the area of the world where resources are scant.