Effects of Renin–Angiotensin Blockade on the Components of Early Interstitial Expansion in Patients with Type 1 Diabetes
Round 1
Reviewer 1 Report
In this article, authors summarized the results obtained in multicentric studies regarding the effects of renin-angiotensin system inhibition on kidney dysfunction in individuals with type 1 diabetes. Specifically, the study focused on the use of enalapril or losartan for renin-angiotensin system inhibition. The study found that blocking this system did not significantly improve kidney function on these patients, however it did shown an increase in the fractional volume of the renal cortex. It is of interest that the patients who received treatment had a higher urinary albumin excretion rate compared to the control group, although both groups were within the normal range.
The article is well written, introduction and data are well explained and it has an easy to follow continuity. The discussion of the results is thorough and analytic.
In order to help the readers to visualize the data presented in the tables with mean values and deviations, I would advise to present them in the form of column graphs with error bars and dots for individual values. The more significant values to be highlighted are already selectively included in the main text.
Thanks to the authors for your work increasing knowledge for the improvement on diabetes healthcare.
Author Response
Thank you for this suggestion. Please see Figure 1 in the revised manuscript depicting the main parameters at baseline and 5 years in the placebo and treatment groups.
Reviewer 2 Report
This study is unique in that it involved data on kidney biopsy specimens collected from individuals with type 1 diabetes at a time point when no clinical signs of kidney disease were present. This is rare and having data on such samples is valuable. The individuals then received either placebo or RAS blockade and followed for 5 years. Kidney biopsy has been then performed also at the end of the 5-year follow up from the same individuals to compare morphometric data to the baseline. However, no specific clinical information for this 5-year time point has been provided. Notwithstanding the importance of showing biopsy-related results from such unique setting, the study is incomplete without providing the clinical correlate for it at the end of the study.
Specific comments:
· 1) What were the clinical parameters in control and RAS blocker groups at the end of the 5-year-study, i.e., for HbA1c, BP, ACR, GFR and BMI? At baseline, they all have been shown to be similar (table 1)? In the Study Design section, it says that BP, ACR, and HbA1C were obtained quarterly and the GFR was done at baseline, and then every year for 5 years, so this data should likely be available to the investigators. These clinical data would provide a relevant clinical context to the EM data presented already at 5 years.
· 2) It would also be important to show how the renal morphometric structural parameters shown at the baseline in table 2 change over time the way it was shown for interstitial components in table 3.
· 3) The authors have chosen to combine the Enalapril and Losartan groups for analyses reasoning that at the baseline demographic, clinical and renal structural parameters, including Vv(Int/cortex), Vv(Col/int), Vv(PTC/int), Vv(Cell/int), and Vv(Sp/int) were not different between these two treatment groups. Since all groups were matched and the group size of 7 should have been sufficient based on the power assumptions the authors made, it would be interesting to know whether these two treated groups were also not different at the conclusion of the study.
· 4) Numbering of the headings is not clear. The headings for Introduction, Materials and Methods, Results and Discussion all start with the number “1” Please either remove the numbers or change them.
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Round 2
Reviewer 2 Report
The authors addressed all comments and suggestions.
