Utility of Urinary β2-Microglobulin for Detection of Renal Sarcoidosis Without Pulmonary Involvement: A Case Report

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a very well-written case report and warrants publication. Here are some minor issues.

• The paper reports markedly elevated urinary β2MG (33648 μg/l) at presentation; however, time trends before and after therapy (steroid initiation) should be shown numerically and graphically if available. A small timeline figure or table showing serial serum creatinine, eGFR, urinary protein, urinary β2MG, and urinary NAG would strengthen the argument that β2MG paralleled disease activity and response.
• Provide more detail on infectious workup: were acid‑fast bacilli stains, fungal stains, TB PCR, or cultures performed on biopsy tissue? 
• Provide the assay method for urinary β2MG (immunoassay type, manufacturer), storage/handling details (β2MG is labile in acidic urine), and the lab’s reference ranges. This impacts generalizability and reproducibility.
• Explain timing of collection (spot urine vs 24‑hour) and whether urine pH was controlled; urinary β2MG degrades in acidic urine, which affects interpretation.
• The paper reports markedly elevated urinary β2MG (33648 μg/l) at presentation; however, time trends before and after therapy (steroid initiation) should be shown numerically and graphically if available. A small timeline figure or table showing serial serum creatinine, eGFR, urinary protein, urinary β2MG, and urinary NAG would strengthen the argument that β2MG paralleled disease activity and response.
• The current limitations section is brief. Emphasize that this is a single case, that β2MG is a nonspecific tubular marker elevated in many tubular pathologies, and that larger studies are needed. Discuss false positives (other causes of tubulointerstitial nephritis) and false negatives (if pure glomerular disease present).
• Add a sentence: “Urinary β2‑microglobulin is a nonspecific marker of tubular injury and should be interpreted alongside clinical, imaging, and histopathological data.”

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

1. General Assessment

This manuscript presents a case of biopsy-proven renal sarcoidosis without pulmonary involvement, emphasizing the potential utility of urinary β2-microglobulin (β2MG) as an early indicator of tubulointerstitial injury. The topic is clinically relevant, as isolated renal sarcoidosis is rare and frequently underrecognized. The case is well documented, and the histopathological findings are clearly described and supported by figures.

The manuscript provides educational value by highlighting the diagnostic challenge and the risk of misattributing mild creatinine elevation to prerenal causes. However, several issues regarding overinterpretation, differential diagnosis exclusion, timeline clarity, and discussion balance should be addressed before publication.

2. Major Comments

• Overinterpretation of Urinary β2-Microglobulin

The manuscript suggests that routine incorporation of urinary β2MG into follow-up monitoring may facilitate early detection of renal sarcoidosis. While the observation is interesting, the conclusion appears somewhat overstated for a single case report.

• No comparative or longitudinal data are presented.
• The specificity of β2MG for sarcoid-related tubulointerstitial nephritis is not discussed.
• β2MG is elevated in various causes of tubular injury.

Recommendation:
Temper the conclusions and frame the findings as hypothesis-generating. Add a brief discussion of the limitations of β2MG, including the lack of disease specificity.

• Differential Diagnosis: IgG4-Related Disease

The manuscript states that IgG4-related disease was excluded based on normal total IgG and absence of storiform fibrosis. However:

• Serum IgG4 levels were not measured.
• It is unclear whether IgG4 immunostaining was performed.

This weakens the certainty of exclusion.

Recommendation:
Clarify whether IgG4 immunostaining was performed. Modify language from “excluded” to “considered unlikely” if definitive testing was not completed.

 

 

Comments for author File: Comments.pdf

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Most of the comments have been addressed

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors

Thanks for your complete response. I do not have any more questions.