Parametric MRI Detects Aristolochic Acid Induced Acute Kidney Injury
, Guixiang Yang 1,2, Yihao Guo 3, Kaixuan Zhao 1, Shuyu Wu 4, Zhongbiao Xu 5, Shan Zhou 6, Chenggong Yan 2, Erdmann Seeliger 7, Thoralf Niendorf 8, Yikai Xu 2 and Yanqiu Feng 1,9,10,11,*Round 1
Reviewer 1 Report
these are not primary clinical markers to assess kidney damage, creatinine is a lousy kidney marker, urea is not useful as a kidney marker either, so CKD-EPI, cystatin "C", NGAL, RBP and Hepcidin should have been used instead .
4 rats to make statistics are not enough. At least that is how it is interpreted in manuscript.
As previously stated, sCr and BUN levels are not suitable for detecting early nephron damage.
as long as a mapping study is used and compared with correct biochemical markers, the results obtained will be better.
clinical laboratories currently use tests such as cystatin "C" and microalbuminuria as a minimum to detect acute renal failure. So the tests used in this project are not adequate.
the conclusion is invalid, since adequate renal biomarkers for monitoring acute kidney injury have not been used.
if this study had been carried out with the correct biochemical renal markers, then the results would be different. In this study we wanted to highlight the usefulness of MRI, but with erroneous results of urea, BUN and serum creatinine. As an interesting fact, the elevated values ​​of these biomarkers appear elevated when the kidney is damaged by more than 50%.
An interesting fact that should be included is the cost-benefit of MRI vs. biochemical markers.
The authors demonstrate in this project that they are not up to date in clinical laboratory tests to contribute to the diagnosis of acute renal failure.
Comments for author File: 
Comments.pdf
Author Response
Dear reviewer,
Please see the attachement.
Author Response File: Author Response.pdf
Reviewer 2 Report
1. Line 4: Zhongbiao Xu 4
2. Line 82: Please add the IACUC No. for this study.
3. Line 141: …The serum was stored at -80℃ for sCr and BUN measurements. sCr and BUN levels were measured. However, measure new renal biomarkers KIM1, and albumin as well as BUN, sCr, in urine samples showing tubular toxicity in animals.
4. For the renal toxicity study, the kidney absolute (g) and relative (%) weights are important indicators in rats, please provide and compare it on each time course.
5. It is hard to read on Fig. 6. The x- and y-axis, scales and background left to be remake. The elevation of these metrics was not detected until day 4 (sCr at day 4 and BUN at day 6) when tubular necrosis was shown. Did this toxicity be reversible or not?
6. Line 147-153: The determinative criteria may be presented by a sheet, to show and compare which lesion is present. Although the tubular injury score (TIS) was carried out. However, it is hard to define the severity levels in the AA kidneys. For the toxicopathology, the semi-quantitative scoring is recommended by Shackelford et al. (2002). The degrees of lesions in each item are graded from one to five depending on severity: 1 = minimal (< 1%); 2 = slight (1-25%); 3 = moderate (26-50%); 4 = moderate/severe (51-75%); 5 = severe/high (76-100%). Finally, summarizations as mean and standard deviation on each lesion and sum of all severity scores are recommended for statistically comparison among groups at p < 0.05 in Figure 7 or a Table.
7. Figure 7: The mark (triangle, long arrow, arrowhead and asterisk) may be added in the description of Fig. 7 legend.
8. It is not clear what severity scores of TIS on day 2, 4 and 6 on Fig. 8. Please define the severity grades of minimal or severe/high of AKI toxicity, based on the toxicopathologic criteria, on day 2, 4 and 6.
9. Please recheck the characters of uppercase or lowercase in the cited references, such as: 14. …The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy.
Author Response
Dear reviewer,
Please kindly see the attachment. Thanks.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
I appreciate the feedback, I consider that the adjustments made to the article improved its quality and scientific solidity.
Reviewer 2 Report
No more questions, except black-dark color in background still found and hard to read on Fig. 6. on page 7. Please recheck it.
