Review Reports - Recurrence and Outcomes of Lupus Nephritis After Renal Transplantation: Analysis of Nine Cases and Review of the Literature

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Recurrence Protocol: You must create a dedicated subsection in the Methods to define "post-transplant LN recurrence." You need to specify if it was biopsy-proven or clinical, how you ruled out competing causes (rejection, CNI toxicity, infection), and whether biopsies were "for-cause" or "protocol."

Transplant Details: Provide specific data on induction therapy, maintenance immunosuppression, and target drug troughs for the 9 KT patients.

Cohort Selection: Clarify how patients were identified (e.g., ICD codes vs. registry) and how you defined the transition from LN to ESRD.

The sample size of 9 is too small to draw any conclusions regarding independent predictors of LN recurrence.

Can use swimmer's plot to track each patient’s journey from transplant to recurrence, rejection, or graft loss.

Ensure terminology is uniform (e.g., consistently use "recurrence" over "relapse," and "KT" for kidney transplant).

Author Response

Reviewer 1

General response:

The authors would like to thank Reviewer 1 for the thorough evaluation of our work and for the valuable comments that contributed to improving the manuscript.

Response:

Thank you for this important comment. A dedicated subsection defining post-transplant lupus nephritis recurrence has been added to the Methods section. We now clearly specify that recurrence was biopsy-proven, describe the clinical indications for kidney biopsy (for-cause biopsies), and explain how alternative causes of graft dysfunction including acute rejection, calcineurin inhibitor toxicity, and infection were systematically excluded.

Transplant Details: Provide specific data on induction therapy, maintenance immunosuppression, and target drug troughs for the 9 KT patients.

Response:

Thank you for this comment. Detailed information on induction therapy, maintenance immunosuppressive regimens, and target trough levels for immunosuppressive agents in kidney transplant recipients with LN has now been added to the Results section.

Cohort Selection: Clarify how patients were identified (e.g., ICD codes vs. registry) and how you defined the transition from LN to ESRD.

Response:

Thank you for this comment. Patients were initially identified using the ICD-10 code M32. In a second step, the diagnosis of systemic lupus erythematosus was confirmed according to the EULAR/ACR 2023 classification criteria. The definition of progression from lupus nephritis to end-stage renal disease has now been clearly specified in the Methods section.

The sample size of 9 is too small to draw any conclusions regarding independent predictors of LN recurrence.

Response:

We fully agree with the Reviewer. Accordingly, the Discussion and Conclusions were revised to ensure that interpretations and recommendations are based primarily on existing literature rather than on the limited number of transplant recipients included in our cohort.

Can use swimmer's plot to track each patient’s journey from transplant to recurrence, rejection, or graft loss.

Response:

Thank you for this helpful suggestion. A swimmer’s plot illustrating each patient’s clinical course from kidney transplantation to LN recurrence, graft loss, or death has been added to the Results section.

Ensure terminology is uniform (e.g., consistently use "recurrence" over "relapse," and "KT" for kidney transplant).

Response:

Thank you for this comment. Terminology has been standardized throughout the manuscript. We now consistently use the term “recurrence” to describe post-transplant lupus nephritis, as this term is more appropriate in the transplantation setting and is commonly used in the literature to indicate disease reappearance in the allograft. We avoided abbreviations for kidney transplantation to maintain clarity, given the variability of abbreviations used across studies.

We hope that the revised version of the manuscript is now suitable for publication. Thank you very much for your time and consideration.

Reviewer 2 Report

Comments and Suggestions for Authors

This study is relevant as it examines kidney transplantation outcomes in typically young patients with lupus nephritis. The primary limitation is the small sample size of nine cases, which prevents robust statistical analysis and assessment of associations between lupus nephritis subtypes and post-transplant recurrence risk. However, the manuscript is well written and offers a thorough review of the existing literature. Comments

Consider revising the title to “Relapse and Outcomes of Lupus Nephritis After Renal Transplantation: Analysis of Nine Cases and Review of the Literature,” or a similar version, to more accurately reflect the manuscript’s content.
In the Discussion section, please base recommendations primarily on the existing literature rather than on findings from the nine reported cases.
The observed mortality rate among patients with relapsed lupus nephritis appears high, likely due to the small sample size, which limits statistical analysis. Please clearly acknowledge this limitation, as well as the overall mortality rate of transplanted patients at your center, in the revised manuscript.
Including a follow-up algorithm that outlines your perspective and recommendations for managing these patients would be a valuable addition to the manuscript.

Author Response

Reviewer 2

General response:

The authors would like to thank Reviewer 2 for the comprehensive assessment of our work and for the valuable comments, which helped improve the manuscript.

Response:

We agree that the small number of transplant recipients limits statistical analyses. As clarified in the revised manuscript, the study was conducted within a large cohort of 1,039 patients with systemic lupus erythematosus followed for a median of over 10 years, among whom 28 developed end-stage renal disease and 9 subsequently underwent kidney transplantation. While limited, we believe these cases provide clinically relevant observations when interpreted in the context of existing literature.

Consider revising the title to “Relapse and Outcomes of Lupus Nephritis After Renal Transplantation: Analysis of Nine Cases and Review of the Literature,” or a similar version, to more accurately reflect the manuscript’s content.

Response:

Thank you for this suggestion. The title has been revised in accordance with the Reviewer’s recommendation to more accurately reflect both the case series and the literature review.

In the Discussion section, please base recommendations primarily on the existing literature rather than on findings from the nine reported cases.

Response:

We thank the Reviewer for this comment. The Discussion and Conclusions were revised to ensure that clinical recommendations are derived primarily from published evidence rather than from observations in the nine reported cases.

The observed mortality rate among patients with relapsed lupus nephritis appears high, likely due to the small sample size, which limits statistical analysis. Please clearly acknowledge this limitation, as well as the overall mortality rate of transplanted patients at your center, in the revised manuscript.

Response:

Thank you for this important comment. We now explicitly acknowledge that the apparently high mortality among patients with recurrent LN is likely influenced by the very small sample size, which limits meaningful statistical interpretation. Due to the retrospective design and scope of data collection, overall mortality data for all kidney transplant recipients at our center were not available and therefore could not be analyzed; this limitation has been clearly stated in the revised manuscript.

Including a follow-up algorithm that outlines your perspective and recommendations for managing these patients would be a valuable addition to the manuscript.

Response:

We thank the Reviewer for this insightful suggestion. Given the very limited number of kidney transplant recipients with recurrent lupus nephritis in our cohort, we believe that proposing a formal follow-up or management algorithm based on these data alone would not be sufficiently evidence-based. This limitation has now been explicitly acknowledged in the Limitations section. Nevertheless, we expanded the Discussion to summarize follow-up strategies and management approaches suggested in the existing literature, which may help guide clinical practice.

We hope that the revised version of the manuscript is now suitable for publication. Thank you very much for your time and consideration.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

This is a clinically relevant, single-center retrospective case series of patients with LN who underwent kidney transplantation, with a narrative literature component. The manuscript is readable, and the topic is appropriate for the journal. The main concern is that the study’s inferential value is limited by the very small transplant cohort (n=9). With nine patients, any associations (risk factors, antibody relationships, recurrence predictors) should be framed as descriptive observations only, not inferences.

Author Response

Reviewer 1

Response:

We sincerely thank the Reviewer for this important and constructive comment. We fully agree that the transplant cohort is relatively small (n = 9), which limits the inferential strength of the study. Although the overall lupus nephritis (LN) cohort included approximately 1000 patients, only 28 progressed to end-stage kidney disease, and unfortunately, only 9 underwent kidney transplantation. We agree that, given this sample size, any associations observed should be interpreted as descriptive rather than inferential. Accordingly, we have revised the manuscript to ensure that all findings related to the transplant cohort are presented as descriptive observations. We have also explicitly added this as a limitation in the “Limitations of the Study” section. We appreciate the Reviewer’s thoughtful feedback, which has helped us improve the clarity and rigor of the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors addressed all issues.

Author Response

Reviewer 2

Response:

We sincerely thank the Reviewer for the careful reassessment of our manuscript and for the positive feedback. We greatly appreciate the time and effort invested in evaluating our work.