S-Methyl-L-Ergothioneine to L-Ergothioneine Ratio in Urine Is a Marker of Cystine Lithiasis in a Cystinuria Mouse Model
, Lourdes Muñoz 3, Ciriaco Carru 4, Salvatore Sotgia 4, Angelo Zinellu 4, Carmen Serra 3, Amadeu Llebaria 3,5, Yukio Kato 6 and Virginia Nunes 1,2,7,*Round 1
Reviewer 1 Report
The authors investigated urinary markers to detect or diagnose cystine stones using a mouse model of cystinuria. This is a very interesting study and is well done. I have only a few questions about this study. My concerns are:
- Since this study uses a mouse model, the authors need to show how well this mouse model fits into human cystinuria to avoid objections caused by species-specific properties. Can the ratio of S-methyl-L-ergothioneine to L-ergothioneine in urine be measured with as much effort as the current method, crystalluria analysis, in patients with cystinuria?
- Can the author argue that this method still overcomes current diagnostic methods, despite differences due to species characteristics, such as the gender differences seen in this model?
Author Response
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Author Response File: 
Author Response.docx
Reviewer 2 Report
Heredia et al. investigated the urinary S-methyl-L-ergothioneine to L-ergothioneine ratio in a cystinuria mouse model. It helps to discriminate between cystine lithiasis phenotypes and is considered a biomarker. I have some suggestions for this study.
1. Please provide the case numbers in each group (Slc7a9-/- male/female mouse model and WT male/female mouse model). Besides, the case numbers of L-Erg and S-Met-L-Erg levels measurement in each group are also needed.
2. The urine S-methyl-L-ergothioneine to L-ergothioneine ratio in clinical research could be discussed and strengthened the application.
3. Since the L-ergothioneine could be measured in blood, plasma, RBC, and urine, is it possible to measure circulating S-methyl-L-ergothioneine (whole blood or plasma)?
4. Urine S-Met-L-Erg / L-Erg ratio has an excellent performance in distinguishing stone former and non-stone former in overall mice. How about the receiver operator characteristic curve in male and female mice separately? Besides, urinary S-Met-L-Erg / L-Erg ratio could be presented in cystinuric mice at 3 and 6 months of age. Besides, sex stratification results of urinary S-Met-L-Erg / L-Erg ratio at 3 and 6 months of age could also be presented.
Author Response
Please see the attachment
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
All suggestions had been revised accordingly. I have no further comments for this paper.
