Comparative Analysis of Graft Survival in Older and Younger Kidney Transplant Recipients: A Single-Center Cohort Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this interesting and clinically relevant manuscript evaluating 10-year single-center outcomes of older kidney transplant recipients. The authors address an important and growing area in transplantation, and the use of competing risk methodology is a notable strength.

Below are detailed comments aimed at improving clarity, methodological robustness, and overall impact of the work.

Major Comments

1. Novelty and positioning of the study

The manuscript states that prior literature has shown worse graft survival among older recipients, whereas your results show no significant difference. This is a key message; however, the novelty could be more clearly articulated in the Introduction and Discussion.
Please more explicitly state:

• how donor characteristics (older donors) differ from previous cohorts,
• why your center’s selection process for older candidates may differ from prior studies, and
• what new knowledge your findings contribute to current clinical decision-making.

2. Clarification of donor characteristics and quality

Your cohort included donors with a median age of 58 years, substantially older than in many previous studies. This likely influences outcomes and selection practices.
Please elaborate:

• How donor age distributions differed between older vs younger recipients (Table 2 shows significant differences but interpretation could be expanded).
• Whether KDPI or other donor quality indices are available.
• Whether donor comorbidities (hypertension, diabetes, etc.) were recorded.

3. Competing risk framework – need for clearer explanation

Although the Fine–Gray competing risks model is appropriate, the rationale may not be fully clear to all readers.
Please clarify the following:

• Why death-censored graft failure overestimates graft failure in this setting.
• Why the cumulative incidence function (CIF) is preferable.
• Whether proportional subhazards assumptions were adequately checked (you mention Schoenfeld residuals but these apply to Cox models; please clarify what diagnostic was used for Fine–Gray).

4. Variable selection for multivariable models

Candidate variables were selected with p<0.2 plus known clinical covariates.
However, several important variables appear missing:

• Delayed graft function (DGF)
• Number of HLA mismatches
• Induction and maintenance immunosuppressive regimen
• Frailty/geriatric indicators (acknowledged as a limitation)

Even if unavailable, please provide clear justification for exclusion and discuss possible confounding.

5. Interpretation of findings regarding graft survival

Your main result—comparable graft survival despite older donor age, more comorbidities, and higher complication rates—is clinically meaningful.
However, more nuanced interpretation is needed:

• Could selection bias (healthier older adults accepted for transplantation) partially explain the findings?
• Could lower competing risk of death in younger cohort affect comparison?
• Provide more discussion on why older recipients did not show worse KGF despite risk factors.

6. Figures require improvement for readability

Figures 1 and 2 (CIF and KM curves) are informative but the following improvements are recommended:

• Increase resolution and line thickness for better clarity.
• Add number-at-risk table for Figure 1 as done for Figure 2.
• Provide explicit legend text rather than relying on color alone.
• Ensure color scheme is accessible for readers with color-vision deficiency.

Minor Comments

Introduction

• Lines 44–56: The epidemiological statements are correct but somewhat lengthy. Consider tightening to better lead into the research question.

Methods

• Clarify whether all transplants used the Taguchi technique throughout the entire decade.
• Please state if immunosuppressive protocols changed over the study period.

Tables

• Table 1 and 2 contain valuable information but formatting could be improved for readability.
• Please ensure consistent decimal usage (some variables mix mean/SD and median/IQR; consider standardizing).
• Provide p-values for all comparisons in Table 2 using consistent notation.

Results

• Line 148: State explicitly whether deaths before graft failure were treated as competing events (though implied).
• Provide crude incidence rates (KGF per 100 patient-years), which help contextualize findings.

Discussion

• Some references are duplicated or appear twice (e.g., [8] vs [30]).
• Consider adding brief comments on whether living donor kidney transplant outcomes in older adults differ, even though your cohort is deceased-donor only.

Conclusion

• Strong and clear, but could be strengthened by briefly highlighting clinical implications for transplant selection committees.

English and Stylistic Suggestions (Optional)

• Minor grammatical edits throughout would enhance readability.
• Consider revising long paragraphs in the Discussion into shorter, more focused segments.

Overall Assessment

• Strengths: Use of competing risks, decade-long dataset, clinically relevant population, sensitivity analysis using ≥65 and ≥70 thresholds.
• Limitations: Missing key confounders, potential selection bias, single-center design, limited granularity on donor factors.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The work addresses the issue of kidney transplantation in the elderly and in the era of an aging society this type of research is extremely important.

The primary outcome was 60-month KGF.

All consecutive deceased donor kidney transplant patients operated from 2011 to 2021 were included into the study.

The follow-up time started on the date of KT and ended on the date of KGF, the date of data extraction (December 31, 2022), death, or, for censored patients, the date of last follow-up, whichever occurred first.

This indicates that in a significant percentage of patients, the primary outcome could not be assessed because the follow-up time was less than 60 months (the IQR of follow-up was 28-83 months for the entire cohort and 38-92 monthsw for event-free patients).

I suggest setting a minimal follow-up period of 60 months for all patients (completing the data until 2026) and re-analyzing the data.

 

Additional remarks

For the reasons described above, the title suggesting a 10-year observation period is misleading.

There are no data on immunosuppressive treatment.

Empty columns and rows in tables should be removed.

Results should be placed in a separate section, not in Materials and Methods.

Author Response

We appreciate the opportunity to submit a revised draft of our manuscript titled “Comparative Analysis of Graft Survival in Older and Younger Kidney Transplant Recipients: A 10-Year Single-Center Cohort Study” for consideration as an original article in the Journal of Clinical Medicine.

We appreciate the time and effort that you and the reviewers have dedicated to our manuscript. We are grateful to the reviewers for their helpful comments:

REVIEWER 2

 

Comments 1:  This indicates that in a significant percentage of patients, the primary outcome could not be assessed because the follow-up time was less than 60 months (the IQR of follow-up was 28-83 months for the entire cohort and 38-92 months for event-free patients). I suggest setting a minimal follow-up period of 60 months for all patients (completing the data until 2026) and re-analyzing the data.

 

Response:  We thank the reviewer for this valuable observation and fully agree that the relevant outcome time point is 60 months. As indicated in the Methods section, the primary endpoint was indeed the 60‑month kidney graft outcome. What may have caused some confusion is the distinction between the cohort’s recruitment period and the timeframe used for outcome analysis, which represent two separate temporal dimensions.

 

Comments 2: For the reasons described above, the title suggesting a 10-year observation period is misleading.

 

Response: We appreciate the reviewer’s concern regarding the potential interpretation of the title. As previously clarified, the title "Comparative Analysis of Graft Survival in Older and Younger Kidney Transplant Recipients: A 10-Year Single-Center Cohort Study" refers to the recruitment period of the study rather than the outcome time point. The primary endpoint was the 60‑month graft survival, as specified in the Methods section. Importantly, the use of censored data analysis allows for the inclusion of patients with shorter follow-up durations without introducing bias or misleading results, which is precisely the methodological principle underlying censored data analysis.

 

Comments 3: There are no data on immunosuppressive treatment.

 

Response:

We acknowledge that the absence of data on immunosuppressive treatment represents an important limitation, along with other variables not captured in our database. As noted in the Discussion section, “the variable selection for multivariable analysis was performed based on the literature and the available data in our database. However, some variables were not recorded, and unmeasured confounders such as delayed graft function and the number of HLA mismatches were not accounted for. Despite these variables having been associated with kidney graft failure in previous meta‑analyses, the effect size and the degree of certainty of their impact are moderate.”

Furthermore, in the meta‑analysis by Forouad et al. on risk factors for 1‑year graft loss after kidney transplantation, 35 studies were analyzed, encompassing 20 risk factors amenable to meta‑analysis. Using meta‑analytic estimators to assess effect magnitude and the GRADE approach to evaluate certainty of evidence, the authors found no significant association between immunosuppressive regimen and the risk of graft loss.

 

Foroutan F, Friesen EL, Clark KE, Motaghi S, Zyla R, Lee Y, Kamran R, Ali E, De Snoo M, Orchanian-Cheff A, Ribic C, Treleaven DJ, Guyatt G, Meade MO. Risk Factors for 1-Year Graft Loss After Kidney Transplantation: Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol. 2019 Nov 7;14(11):1642-1650. doi: 10.2215/CJN.05560519. Epub 2019 Sep 20. PMID: 31540931; PMCID: PMC6832056.

 

 

Comments 4: Empty columns and rows in tables should be removed.

 

Response: Agree: We agree with the reviewer’s observation. The empty columns and rows will be removed during the editorial process.

 

Comments 5: Results should be placed in a separate section, not in Materials and Methods.

 

Response: We agree with the reviewer’s observation. The placement of the Results section within Materials and Methods appears to be a formatting issue that occurred during post‑processing of the manuscript. This will be corrected during the editorial process to ensure that the Results are presented in a separate section, as intended.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed all previous comments thoroughly and with great care.
The revised manuscript is clear, well-organized, and the responses demonstrate a solid understanding of the methodological and clinical points raised during the first review.

The additional explanations regarding donor characteristics, the center’s selection process, and the interpretation of competing risk analyses have strengthened the clarity and scientific rigor of the work. The revisions to the figures and the refinements made in the Introduction and Discussion sections have also improved readability and coherence.

I have no further suggestions for improvement.

Author Response

We sincerely thank the reviewer for their thorough evaluation and constructive feedback throughout the review process. We are pleased to know that the revised manuscript is now considered clear and well-organized, and that our responses have adequately addressed the methodological and clinical points raised in the first round.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors' explanations regarding the study's methodology fail to address my most important objections: suggesting a ten-year follow-up period in the title and assuming a 60-month assessment as the study's aim, they provide estimated results based on a much shorter follow-up period.

 

Author Response

Reviewer: The authors' explanations regarding the study's methodology fail to address my most important objections: suggesting a ten-year follow-up period in the title and assuming a 60-month assessment as the study's aim, they provide estimated results based on a much shorter follow-up period.

Response: 

We thank the reviewer for their careful reading and comments. We would like to clarify a possible misunderstanding regarding the study’s design.

The ten‑year period mentioned in the manuscript refers to the duration of patient recruitment, not to the follow‑up time for the primary endpoint. The analysis of the study endpoint was intentionally set at 60 months, which corresponds to the pre‑specified time horizon for assessing outcomes.

To avoid any ambiguity, we have modified the title of the manuscript to explicitly reflect the recruitment period and the 60-month endpoint assessment. We believe this change resolves the concern and ensures that the methodology is presented with greater clarity.

We appreciate the reviewer’s attention to this point, as it has helped us improve the manuscript's precision.