The Incidence and Correlation of Renal Pathologies Based on 14-Year Kidney Biopsy Material: A Retrospective Single-Centre Study in Poland

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors report biopsy based kidney diagnosis epidemiology in Poland over a recent 15 year period.  Most parameters are in keeping with expected trends.  The study, one assumes, purports to represent biopsy-based kidney disease trends rather than diagnostic intricasies.

It may be worth including:

1.Some measure of disease proportion in relation to overall population - admittedly biopsy based, as well as the population with potential kidney disease.

2.Similar analysis, after dividing the cohort into maybe 2 periods - approximately at the half mark, or considering 3 periods with the covid pandemic as a break point.

3.Overall fine, but better written english will make for better flow and uptake. 

Author Response

Thank you for your assessment. We hope that the changes we have made will facilitate the continued review process of our manuscript. Your feedback has been invaluable, and we appreciate your support.

1.Some measure of disease proportion in relation to overall population - admittedly biopsy based, as well as the population with potential kidney disease.

Lower Silesia has a population of approximately 2.9 million, with a notable percentage aged 65 and older. The prevalence of chronic kidney disease in Poland is around 13%, providing context for our findings.

Our study results indicate significant correlations between the observed disease proportions and regional health statistics, emphasizing the public health implications of kidney conditions.

Additionally, approximately 8% of the Polish population is diagnosed with diabetes, a known risk factor for kidney disease, highlighting the need for targeted public health initiatives in Lower Silesia.

Best regards

Krzysztof Benc 
Similar analysis, after dividing the cohort into maybe 2 periods - approximately at the half mark, or considering 3 periods with the covid pandemic as a break point.

Thank you for the valuable suggestion to  considering the impact of the COVID-19 pandemic. We recognize the importance of analyzing shifts in kidney disease patterns during these different timeframes. 

We are currently evaluating this approach and plan to incorporate the findings into a future publication. Your input is greatly appreciated and will strengthen our research.

Overall fine, but better written english will make for better flow and uptake. 

Thank you for your valuable feedback regarding the clarity of our writing. We appreciate your input and have made the necessary revisions to improve the overall flow and language of the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

In the submitted manuscript, The incidence and correlation of renal pathologies based on 14-year kidney biopsy material, the following are objections and need to be corrected and addressed:

1. The authors should select more appropriate and relevant keywords that accurately reflect their study.

2. In the Materials and Methods section, the name of the nephrology center must be provided.

3. In the abstract, you state: Data from 1969 kidney biopsies were collected, with 1293 native kidney cases analyzed after excluding transplant recipients. - It is essential that the same information be included in the methodology. As written, the methodology gives the impression that all 1969 cases were included in the analysis. I suggest clearly stating the inclusion and exclusion criteria and adding a flow chart.
   Additionally, it is confusing that the cumulative number of cases in Table 1 adds up to 1291, not 1293. Please clarify these discrepancies.

4. When dividing patients into three groups for the analysis of age-related trends in glomerular nephropathies, the total number of cases again appears as 1293.

5. In the descriptions of Figures 2, 3, and 4, it is necessary to define all abbreviations used.

6. The Discussion section is overly long and should be shortened. There is no need to repeat previously described results throughout the discussion.

7. The Conclusion is too general and does not fully correspond to the stated objectives of the study.

Author Response

Thank you for your assessment. We hope that the changes we have made will facilitate the continued review process of our manuscript. Your feedback has been invaluable, and we appreciate your support.

1. The authors should select more appropriate and relevant keywords that accurately reflect their study.

We appreciate the reviewer's suggestion regarding the selection of more appropriate keywords. We have added "epidemiology" to our list of keywords, and we believe that the current set is adequate and relevant to the study.  

In the Materials and Methods section, the name of the nephrology center must be provided

I have added the name of the nephrology center: "Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, Wroclaw." We appreciate your attention to detail.

In the abstract, you state: Data from 1969 kidney biopsies were collected, with 1293 native kidney cases analyzed after excluding transplant recipients. - It is essential that the same information be included in the methodology. As written, the methodology gives the impression that all 1969 cases  were included in the analysis. I suggest clearly stating the inclusion and exclusion criteria and adding a flow chart.
Additionally, it is confusing that the cumulative number of cases in Table 1 adds up to 1291, not 1293. Please clarify these discrepancies.

Thank you for your observations. I have verified and corrected all numerical values related to the biopsies performed.

When dividing patients into three groups for the analysis of age-related trends in glomerular nephropathies, the total number of cases again appears as 1293.

Similarly, all numerical data have been reviewed and corrected to ensure accuracy.

In the descriptions of Figures 2, 3, and 4, it is necessary to define all abbreviations used.

Thank you for your feedback regarding the abbreviations have been defined prior to the references section in the manuscript. We appreciate your attention to detail.

The Discussion section is overly long and should be shortened. There is no need to repeat previously described results throughout the discussion.

In accordance with your recommendation, the Discussion section has been shortened to eliminate redundancy and streamline the content.

The Conclusion is too general and does not fully correspond to the stated objectives of the study

Thank you for your observation regarding the Conclusion section. At this time, I will leave this element unchanged. If you feel that modifications are necessary, I would appreciate any specific guidance on what adjustments you would expect.

I would like to express my gratitude for your thorough review and insightful feedback on the manuscript. Your suggestions have been invaluable in improving the quality of the work. I hope that the current version of the paper meets your expectations, and I would be very grateful for your acceptance of it. Thank you once again for your time and effort in evaluating our study.

Best regards

Krzysztof Benc

Reviewer 3 Report

Comments and Suggestions for Authors

I have entusiastically reviewed the paper of Benc K et a. In this paper authors shown that given CKD’s underdiagnosis and frequent late detection in Poland, updated multicentre studies are needed to better recognize disease patterns and raise public awareness. 

Following my suggesitons: 

-) Several renal pathologies, such as diabetic nephropathy (DN), are often diagnosed clinically without renal biopsy. In this way we lead to an underrepresentation of DN in the cohort. In your analysis, the relatively low frequency of DN, and this is true in other pathologies too, could be misunderstand as an actual decline in incidence, when in reality it reflects diagnostic practice rather than epidemiological trends. To avoid misleading conclusions, the manuscript should explicitly acknowledge that DN is clinically diagnosed in most cases and therefore appears “rare” in biopsy registries. More frequent biopsies in diabetic patients may improve diagnosis. 

-) The most reported diagnosis reflect conditions that require histological confirmation. As a result, this cohort od biopsied patients is not the true epidemiology of chronic kidney disease in the general population. What is the mind of author, is this a selection bias? In this way biopsy registry evidence only a subset of renal pathologies, while common entities such as diabetic nephropathy or nephroangiosclerosis are often diagnosed without biopsy.

-) In ≥65 years, amyloidosis, vasculitis, and membranous nephropathy are mean diagnoses. However, this distribution may be strongly influenced by selection bias (elderly patients are biopsied only when there is a clinical necessity). Other common causes of chronic kidney disease in older (DN, NAS) are often diagnosed clinically without histological confirmation. So, registry data may not reflect the true spectrum of renal disease in this population. Is this a limitation? What is your mind? 

-) Readers should be reminded that the frequency of diagnoses does not relate to their clinical impact in example with ESRD. 

-) The manuscript reports the most frequent diagnoses but does not explore if the distribution is significantly influenced by demographic factors such as sex and age. In example, lupus nephritis is most diagnosed in younger women, FSGS or membranous nephropathy may show different demographic patterns. So my question is: have authors evaluated with all statystical analysis available if common variables such as age or sex are independent influencer of diagnosis? In example a multivariate analysis may assess if age > 65 yrs is an independent factor increasing amyloidosis diagnosis independent from sex or diabetes too. 

-) Fig 1 suggests that elderly patients are biopsied more frequently, whereas younger patients are biopsied less frequently to previous years. This reflects evolutive clinical practice rather than changes in disease epidemiology. Bioptical safety and greater awareness of systemic conditions such as vasculitis or amyloidosis may have encouraged more biopsies in older patients. Moreover, in younger some diagnoses such as lupus nephritis or IgA nephropathy are not needing of hystological confirm for their management. The manuscript should clarify that these trends represent changes in diagnostiical practice rather than sure change in disease prevalence.

-) Fig. 4 shows that vasculitis diagnosis is increased while FSGS and MN are reduced. Are these changes true epidemiological change or are influenced by evolving biopsy practices and diagnostic criteria too? Readers may misunderstand that the observed increase in vasculitis represents a real increase in incidence rather than a consequence of change in clinical practice. 

-) This is a monocentric study: may be a limitation? 

In conclusion in this manuscript authors  conducted a single-centre, retrospective study at a university hospital in southwestern Poland, covering 2010–2024. Data from 1969 kidney biopsies were collected,  within 1293 native kidney cases analysed after excluding transplant recipients. Diagnoses were correlated with patients’ age, sex, presence of diabetes, and temporal trends, and compared with previous studies. Authors concluded that given CKD’s underdiagnosis and frequent late detection in Poland, updated multicentre studies are needed to better recognize disease patterns and raise public awareness.  I congratulate myself with authors for their work and I thank Editor for the opportunity to do the review of this interesting paper. 

Best Regards

Author Response

Several renal pathologies, such as diabetic nephropathy (DN), are often diagnosed clinically without renal biopsy. In this way we lead to an underrepresentation of DN in the cohort. In your analysis, the relatively low frequency of DN, and this is true in other pathologies too, could be misunderstand as an actual decline in incidence, when in reality it reflects diagnostic practice rather than epidemiological trends. To avoid misleading conclusions, the manuscript should explicitly acknowledge that DN is clinically diagnosed in most cases and therefore appears “rare” in biopsy registries. More frequent biopsies in diabetic patients may improve diagnosis. 

Thank you for your valuable observation. You are correct that the low frequency of diabetic nephropathy (DN) in our cohort is largely due to the fact that it is often diagnosed clinically, leading to a reduced reliance on renal biopsy for diagnosis. This point is addressed in the last paragraph of the Discussion section, where we emphasize the implications of clinical diagnosis on the representation of DN in biopsy registries. We appreciate your insight, and we recognize that increasing the number of biopsies in diabetic patients may indeed enhance diagnosis.

The most reported diagnosis reflect conditions that require histological confirmation. As a result, this cohort od biopsied patients is not the true epidemiology of chronic kidney disease in the general population. What is the mind of author, is this a selection bias? In this way biopsy registry evidence only a subset of renal pathologies, while common entities such as diabetic nephropathy or nephroangiosclerosis are often diagnosed without biopsy.

I concur with your assessment that many diagnoses in our cohort are made clinically, resulting in the decision to forgo renal biopsy in certain cases. This limitation indeed reflects a selection bias, as the biopsy registry represents only a subset of renal pathologies. Common conditions such as diabetic nephropathy and nephroangiosclerosis are frequently diagnosed without histological confirmation. We appreciate your insightful observation.

In ≥65 years, amyloidosis, vasculitis, and membranous nephropathy are mean diagnoses. However, this distribution may be strongly influenced by selection bias (elderly patients are biopsied only when there is a clinical necessity). Other common causes of chronic kidney disease in older (DN, NAS) are often diagnosed clinically without histological confirmation. So, registry data may not reflect the true spectrum of renal disease in this population. Is this a limitation? What is your mind? 

I agree with your suggestions. Certain diagnoses remain underrepresented due to the reliance on clinical diagnosis rather than renal biopsy, leading to an underestimation of conditions like diabetic nephropathy and nephroangiosclerosis. However, it is important to note that our center has significantly reduced the percentage of patients for whom we forgo biopsy in recent times. This evolving practice may help provide a more accurate reflection of the spectrum of renal disease in older patients. Thank you for highlighting this important aspect of our study.

Readers should be reminded that the frequency of diagnoses does not relate to their clinical impact in example with ESRD.

Thank you for your insightful feedback. The additional information regarding the relationship between the frequency of diagnoses and their clinical impact has been incorporated into the Conclusion section of the manuscript. Your suggestions have been invaluable in enhancing our work.

”It is essential to remind readers that the frequency of diagnoses presented in this study does not necessarily correlate with their clinical impact, particularly regarding conditions like end-stage renal disease (ESRD). While certain diagnoses may be reported less frequently, this does not imply that they have a lesser impact on patient health or outcomes. Some conditions, despite being diagnosed less often, can lead to significant health issues, including ESRD. Therefore, one should not interpret the data solely in terms of prevalence, as this may mislead the understanding of the clinical consequences of various renal pathologies.”

The manuscript reports the most frequent diagnoses but does not explore if the distribution is significantly influenced by demographic factors such as sex and age. In example, lupus nephritis is most diagnosed in younger women, FSGS or membranous nephropathy may show different demographic patterns. So my question is: have authors evaluated with all statystical analysis available if common variables such as age or sex are independent influencer of diagnosis? In example a multivariate analysis may assess if age > 65 yrs is an independent factor increasing amyloidosis diagnosis independent from sex or diabetes too. 

In our study, we aimed to demonstrate the differences in diagnoses in relation to demographic factors, specifically sex (Figure 3) and age (Figure 2). While we have provided descriptive analyses highlighting these differences, we appreciate your suggestion regarding the need for more comprehensive statistical evaluations, such as multivariate analysis.

Fig 1 suggests that elderly patients are biopsied more frequently, whereas younger patients are biopsied less frequently to previous years. This reflects evolutive clinical practice rather than changes in disease epidemiology. Bioptical safety and greater awareness of systemic conditions such as vasculitis or amyloidosis may have encouraged more biopsies in older patients. Moreover, in younger some diagnoses such as lupus nephritis or IgA nephropathy are not needing of hystological confirm for their management. The manuscript should clarify that these trends represent changes in diagnostiical practice rather than sure change in disease prevalence.

We appreciate your observation. It is important to note that the decrease in the proportion of younger patients undergoing biopsies is only a relative decline and does not reflect a reduction in the actual number of procedures performed. Rather, it is largely influenced by the increasing population of patients aged over 65 years who are being biopsied.

In younger patients, we rarely rely solely on clinical diagnosis; kidney biopsies are also performed to assess disease activity and chronicity.Trends in biopsy rates are not indicative of a decrease in procedures for younger patients, but rather a shift in the demographic composition and clinical aproach of those undergoing biopsy.

Fig. 4 shows that vasculitis diagnosis is increased while FSGS and MN are reduced. Are these changes true epidemiological change or are influenced by evolving biopsy practices and diagnostic criteria too? Readers may misunderstand that the observed increase in vasculitis represents a real increase in incidence rather than a consequence of change in clinical practice.

It is true that membranous nephropathy (MN) is frequently diagnosed clinically, which can lead to an underrepresentation of patients with this diagnosis in biopsy registries.

However, the diagnosis of focal segmental glomerulosclerosis (FSGS) is typically made when there are significant comorbid factors, such as obesity or hypertension, that may complicate the safe performance of a biopsy. In these cases, clinicians may be more likely to suspect secondary FSGS. In our clinic, we routinely perform kidney biopsies in all other situations, which allows for accurate diagnosis and prevents potential biases in the data.

This is a monocentric study: may be a limitation?

Indeed, we acknowledge that this is a monocentric study, and this could be considered a limitation. We plan to expand our research to include additional centers in the future, which would significantly enhance the robustness and generalizability of our findings. 

I would like to express my gratitude for your thorough review and insightful feedback on the manuscript. Your suggestions have been invaluable. I hope that the current version of the paper meets your expectations, and I would be very grateful for your acceptance of it. Thank you once again for your time and effort in evaluating our study.

Best regards

Krzysztof Benc

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

• Instead of using the keyword Chronic Renal Insufficiency, it is better to use chronic kidney disease.

• Honestly, in the revised text I do not see that the name of the nephrology center was added, even though you stated in reply that it was.

• In line 211, the number 1293 is mentioned again.

• Please add track changes to the modifications you made in the discussion section. At the end of the manuscript, there is an unnecessary heading for section 6, Patients. In general, you have a quality paper, but please focus a bit more on the sample size. I agree that there is a discrepancy between the only two samples, that do not affect results, but regardless, scientific writing needs to be precise and accurate.
  Please clarify in response these differences regarding 1291 vs. 1293 patients. I am really willing to do reviews, but I cannot go through all data nor perform statistics instead of you.

Author Response

Instead of using the keyword Chronic Renal Insufficiency, it is better to use chronic kidney disease.

In accordance with the comments, correction have been made.

Honestly, in the revised text I do not see that the name of the nephrology center was added, even though you stated in reply that it was.

There was an issue with compiling the revised version; the correction is now available in the first paragraph of the Materials and Methods section.

In line 211, the number 1293 is mentioned again.

I sincerely apologize for the mistake; the correction has been made.

Please add track changes to the modifications you made in the discussion section. At the end of the manuscript, there is an unnecessary heading for section 6, Patients. In general, you have a quality paper, but please focus a bit more on the sample size. I agree that there is a discrepancy between the only two samples, that do not affect results, but regardless, scientific writing needs to be precise and accurate.

Track changes have been enabled, which highlighted a significant portion of the text that we removed to limit this section and avoid reiterating the results, as suggested.

The heading has been removed.

Thank you very much for your comments. I hope that the corrections made will facilitate the further processing of the publication.

Best regards

Krzysztof Benc

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors

Thank you for your new version of this interesting topic. Ensure to insert the suggested limitations in your discussion. I hope that, after my suggestions and evaluation of other potential reviewers, the paper may be able to be published. Congratulation for your hard work to edit the manuscript. I thank Editor for the oppotunity to do the review of your interesting paper. 

Best Regards. 

Author Response

Thank you very much for your comments. 

Best regards

Krzysztof Benc