The Impact of Socioeconomic Factors on Kidney Transplantation: A Systematic Review of Low- and Middle-Income Countries

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This systematic review is of interest - covering the rates of KRT - kidney replacement therapy - and KT - kidney transplantation - across countries designated as LIMC. The review is timely and generally well performed from a technical standpoint. There are some issues to resolve:   

1. The key issue, which the authors allude to briefly, is the publication bias inherent in this area. The review cannot identify activity that is not published in the literature - be it in grey or traditional published literature. I suggest that the authors review carefully their claims in the paper, to make it clear that the findings are based on published literature only. Another suggestion is to undertake an analysis of the differences between the findings of the literature review and the WHO GODT data in the results section and comment on it in the discussion.   

The addition of KRT to the paper is handled rather too lightly in the methods, since it is not quite clear if this was a separate literature search or a by-product of the primary search. 

The use of the word 'prevalence' is confusing - it is usually taken in the transplantation field to mean patients alive at any particular time point with a functioning kidney transplant, while 'incidence' is the number of transplants undertaken in a given year. These interpretations become a little confusing as one reads the document and need to be clarified. Sometimes it seems as if incidence is being reported as prevalence, or that the word prevalence is taken to mean simply that there is KT activity in the country. 

It would be interesting to know the authors' views on what more can be gleaned from examining the literature on KT with respect to the factors that determine successful KT programs versus those that do not. What is it in the standout success stories that can be seen to be different? What further research is planned?

Author Response

We sincerely appreciate the time and effort you have taken to review our manuscript. Your insightful comments and suggestions have been invaluable in helping us improve the quality and clarity of our work. We have carefully considered each of your points and have made the necessary revisions to address them. Below, we provide detailed responses to your comments, along with the corresponding changes made to the manuscript.

Comment 1. The key issue, which the authors allude to briefly, is the publication bias inherent in this area. The review cannot identify activity that is not published in the literature - be it in grey or traditional published literature. I suggest that the authors review carefully their claims in the paper, to make it clear that the findings are based on published literature only. Another suggestion is to undertake an analysis of the differences between the findings of the literature review and the WHO GODT data in the results section and comment on it in the discussion.   

Response 1: Publication bias is an inherent limitation in all systematic reviews, as the reviewer noted. Since our study does not lend itself to the use of a funnel plot to visually assess publication bias, we can only speculate on its impact in this context.

It is likely that publication bias is present, particularly in countries with low socio-economic status, where limited resources for kidney transplantation and research may lead to underreporting. Therefore, our findings may represent a best-case scenario.

Comment 2: The addition of KRT to the paper is handled rather too lightly in the methods, since it is not quite clear if this was a separate literature search or a by-product of the primary search. 

Response 2: We appreciate the reviewer’s attention to the methodology regarding the inclusion of KRT in the paper. To clarify, during the initial title and abstract screening phase, manually added articles that did not meet the inclusion criteria were excluded. However, in the data extraction phase, we thoroughly reviewed the full texts of cross-referenced articles from the included studies. If these cross-referenced articles contained relevant data on KRT that met our criteria, they were then included in the data extraction process.

We have revised the methods section to better explain this process, ensuring that the distinction between the initial screening and the subsequent inclusion of relevant cross-referenced articles during data extraction is clear.

Comment 3: The use of the word 'prevalence' is confusing - it is usually taken in the transplantation field to mean patients alive at any particular time point with a functioning kidney transplant, while 'incidence' is the number of transplants undertaken in a given year. These interpretations become a little confusing as one reads the document and need to be clarified. Sometimes it seems as if incidence is being reported as prevalence, or that the word prevalence is taken to mean simply that there is KT activity in the country. 

Response 3: Author Response: We appreciate the reviewer's feedback regarding the use of the term "prevalence." In the manuscript, we used "prevalence" to refer to all existing cases (functioning kidney cases) of kidney transplantation (KT) or end-stage renal disease (ESRD), not just new cases within a specific year. We recognize that this may have led to some confusion, as the term "prevalence" in the transplantation field typically refers to the number of patients alive at a particular time point with a functioning kidney transplant.

Comment 4: It would be interesting to know the authors' views on what more can be gleaned from examining the literature on KT with respect to the factors that determine successful KT programs versus those that do not. What is it in the standout success stories that can be seen to be different? What further research is planned.

Response 4: Thank you for this thought-provoking question. In the discussion section, we have expanded on the factors that appear to contribute to the success of KT programs in certain LMICs. Our analysis suggests that elements such as healthcare infrastructure, government support, public awareness, and availability of trained professionals play crucial roles in the success of these programs. Additionally, we plan to conduct further studies that could explore the impact of socioeconomic and cultural factors on the success of KT programs.

Reviewer 2 Report

Comments and Suggestions for Authors

Authors present an important study, in which they analyze current status in kidney transplantation and low and middle income countries. This subject is extremally important, since almost no data are available regarding this subject. Manuscript adds important data about transplantation status, however some questions remain to be answered:

1) please explain abbreviation ISI in the text;

2) Figure 2: please add in the caption that this relates to low- and middle-income countries;

3) please explain what is a 'Human Development Index' (P9L183-184);

Comments on the Quality of English Language

Some minor errors can be found, 'electronice' (P2L89), 'researchs' (P3L122), 'were 13 articles were selected' (P3L142-143) 'continets' (P4L152).

Author Response

Comment 1: please explain abbreviation ISI in the text;

Response 1: Thank you for bringing this to our attention. We have added an explanation of the abbreviation "ISI" in the text where it first appears. ISI stands for the "Institute for Scientific Information," which is part of the Web of Science database. This clarification has been made in the methods section of the manuscript.

Comment 2: Figure 2: please add in the caption that this relates to low- and middle-income countries;

Response 2: We appreciate the suggestion to clarify the figure caption. We have revised the caption of Figure 2 to explicitly state that the data presented relate to low- and middle-income countries (LMICs). The updated caption now reads: "Global Distribution of Kidney Transplantation Prevalence in Low- and Middle-Income Countries."

Comment 3: please explain what is a 'Human Development Index' (P9L183-184);

Response 3: The HDI is a composite statistic of life expectancy, education, and per capita income indicators, which are used to rank countries into four tiers of human development. We have added a brief explanation in the text (P9L184-185)

Comments: Some minor errors can be found, 'electronice' (P2L89), 'researchs' (P3L122), 'were 13 articles were selected' (P3L142-143), 'continets' (P4L152).

Reponse: Thank you for pointing out these minor errors. We have corrected the typographical errors as follows:

"electronice" (P2L89) has been corrected to "electronic."

"researchs" (P3L122) has been corrected to "research."

"were 13 articles were selected" (P3L142-143) has been corrected to "there were 13 articles selected."

"continets" (P4L152) has been corrected to "continents."

Thank you very much for your comments.

Reviewer 3 Report

Comments and Suggestions for Authors

Authors conducted a retrospective review of published literature on the disparities in KT access and prevalence in LMICs. They found that LMICs had significant barriers to 

  Questions 1) What dates were included in the search? Manuscript says up to May 2024, but what was the earliest study date of all the manuscripts included in the SR? 2) When reporting GNI data, was that pegged to a specific time (eg May 2024) or to the time of study publication? 3) how were studies validated to ensure reported data was truly NATIONAL data and not just regional, institutional data? Were there any other references to cross validate reported prevalence rates of KRT/KT at the time of publication? 4) Fig 3 shows KT rates correlate with GNI. How about KRT rates and GNI? 5) were there any associations between year of publication and KRT/KT rates? Any correlation between year of publication and GNI per capita or geography/region? 6) how do KT rates, in the context of KRT rates, correlate with LMIC based on GNI?   Comments
There were 22 additional articles added from manual review, almost double the final list included from the original search criteria. What made them unidentifiable in the original search screening? How does that make the data in those 22 studies different and could that influence the study results?   What proportion of studies were reporting on prevalnaces in a country with longstanding KT programs vs those that were reporting on their “early” outcomes after newly implementing KT programs?   Are your findings a surprise? Or would you have expected to find this a priori? I think your findings are simply a surrogate marker of the healthcare systems as a whole in these LMIC. Without further granular details, it will be hard to tease out the exact reasons for KT/KRT specific limitations. 

Author Response

We sincerely appreciate the time and effort you have invested in reviewing our manuscript. Your thoughtful comments and suggestions have been instrumental in enhancing the quality and clarity of our work. Below, we provide detailed responses to your comments, along with the corresponding changes made to the manuscript.

Comment 1: What dates were included in the search? Manuscript says up to May 2024, but what was the earliest study date of all the manuscripts included in the SR?

Response 1: Thank you for your question regarding the date range of the studies included in our systematic review. The literature search covered all relevant studies published up to May 2024. The earliest study included in our review was published in 1976. We have updated the manuscript to clarify this information.

Comment 2: When reporting GNI data, was that pegged to a specific time (eg May 2024) or to the time of study publication?

Response 2: Thank you for your question regarding the timing of the Gross National Income (GNI) data. The GNI data reported in our study was pegged to the time of each study's publication

Comment 3: How were studies validated to ensure reported data was truly NATIONAL data and not just regional, institutional data? There were 22 additional articles added from manual review, almost double the final list included from the original search criteria. What made them unidentifiable in the original search screening? How does that make the data in those 22 studies different and could that influence the study results?

Response 3: Thank you for your insightful question regarding the validation of data to ensure it was truly national. During our review process, we were particularly cautious in differentiating between national data and regional or institutional data.

To ensure the accuracy and relevance of our findings, we excluded any studies where there was uncertainty about whether the data represented national statistics. Our guiding principle was that underestimating the scope of national kidney transplantation (KT) and kidney replacement therapy (KRT) activity is preferable to overestimating, as this approach avoids inflating the perceived coverage or success of KT programs in low- and middle-income countries (LMICs). Consequently, if a study did not explicitly confirm that the data reflected national figures or if it was unclear whether the data could be generalized to the entire country, we excluded it from our analysis.

Furthermore, we did not initially have a specific column in our data extraction form to categorize whether the data was national, regional, or institutional. However, during the exclusion process, we documented the reasons for exclusion, specifically noting if the data was regional or institutional, to ensure that only national data was included. This stringent criterion sometimes led to the exclusion of potentially relevant studies.

To address any gaps, we manually added articles identified through cross-referencing during the data extraction phase. These articles, which may not have been captured in the initial search or were initially excluded, were thoroughly reviewed to confirm they met our criteria for national data. If they provided reliable and relevant national-level information, they were included in our final analysis. Twenty-two articles that were manually added, were intially excluded in the screening phase.

This careful approach ensured that our findings are based on the most accurate and representative data available, providing a more reliable understanding of the state of KT and KRT in LMICs.

Comment 4: Fig 3 shows KT rates correlate with GNI. How about KRT rates and GNI?

Response 4: Thank you for your observation regarding the correlation between kidney transplantation (KT) rates and Gross National Income (GNI). In addition to the analysis of KT rates, we found a similar correlation between KRT rates and GNI. To better illustrate this relationship, we have added a new figure to the manuscript that specifically shows the correlation between KRT rates and GNI. This figure further supports the association between a country’s economic status and its KRT rates, reinforcing the impact of GNI on access to and availability of kidney replacement therapies.

Comment 5: Were there any associations between year of publication and KRT/KT rates? Any correlation between year of publication and GNI per capita or geography/region?

Response 5: Thank you for your question regarding the potential associations between the year of publication and KRT/KT rates, as well as any correlation with GNI per capita or geography/region.

Unfortunately, we were unable to identify any clear correlations between the year of publication and KRT/KT rates or GNI per capita. This limitation is primarily due to the lack of longitudinal studies within the same country over time, which would be necessary to make meaningful comparisons. The studies included in our review often reflect cross-sectional data from different countries and regions at various points in time, which are innable to analyze trends or establish correlations across years.

As a result, while we recognize the importance of such correlations, the current dataset does not allow us to draw any definitive conclusions regarding the association between publication year, KRT/KT rates, GNI per capita, or geography/region. Future research with a more longitudinal approach may be necessary to explore these potential relationships.

Comment 6: how do KT rates, in the context of KRT rates, correlate with LMIC based on GNI?

Response 6: Thank you for your question regarding the correlation between kidney transplantation (KT) rates and kidney replacement therapy (KRT) rates in low- and middle-income countries (LMICs) based on Gross National Income (GNI).

In our analysis, we observed that higher GNI within LMICs tends to be associated with both higher overall KRT rates and higher KT rates. However, when examining KT rates in the context of KRT rates (i.e., the proportion of KRT patients receiving KT), we found that countries with higher GNI typically have a greater emphasis on KT as a component of their KRT programs. This suggests that as GNI increases, there is a stronger capacity to perform KT relative to other forms of KRT, such as dialysis.

Comment 7: What proportion of studies were reporting on prevalnaces in a country with longstanding KT programs vs those that were reporting on their “early” outcomes after newly implementing KT programs?   Are your findings a surprise? Or would you have expected to find this a priori? I think your findings are simply a surrogate marker of the healthcare systems as a whole in these LMIC. Without further granular details, it will be hard to tease out the exact reasons for KT/KRT specific limitations. 

Response 7: Thank you for your insightful feedback on our systematic review. We appreciate your observations and agree that the limited number of publications poses a challenge in drawing comprehensive conclusions about kidney transplantation (KT) and kidney replacement therapy (KRT) in low- and middle-income countries (LMICs).