Are the Currently Available Elastography Methods Useful in the Assessment of Chronic Kidney Disease? A Systematic Review and a Meta-Analysis
, Milena Chiodan 1,2,*, Alexandru Sircuta 1,2, Adalbert Schiller 1,2, Ligia Petrica 1,2 and Flaviu Bob 1,2Round 1
Reviewer 1 Report
Interesting topic - thank you for your efforts in contributing to the literature on this topic. However, there are methodological weaknesses. The focus on only one ultrasound elastography method, Virtual Touch Quantification (VTQ), remains unclear.
Nevertheless, a good idea for summarizing the evolving field in renal elastography.
I have provided a few thoughts for your consideration or modification.
General comment:
KSWS is an uncommon abbreviation. SWS is a stand should be used.
Title
Confusing. This work is focusing on VTQ. The results presented do allow an overall elastography conclusion.
Abstract
Modifications according to the following comments.
Introduction
The introduction should elaborate a little better on the need for quantitative imaging. For example, stating the sensitivity/specificity of conventional ultrasound imaging (including references) could emphasize this need.
Elastography is often compared to clinical palpation. However, the phrase “Elastography, a new ultrasound based approach, can be used to gather more detailed information that integrates palpation within ultrasound imaging” remains confusing, since palpation is not really integrated. A technical background related to shear wave speed should be added to the manuscript.
„The advantage over serologic methods could be that the results can be obtained in real-time during a patient visit without the need to wait for laboratory findings.” This is not an advantage with clinical relevance. Laboratory results are available within 24 hours. Creatinine and proteinuria, the most relevant parameters are usually available within hours. The advantages should be better elaborated.
Methods:
Important methods such as time-harmonic elastography (THE) is entirely missing. One high-impact publication focusing on CKD should be referenced and discussed (doi: 10.1148/radiol.2019182574).
One of the renal elastography pioneers, Stock et al., might be added by citation (doi: 10.3233/CH-2011-1503 / 0.3233/CH-2010-1340)
Did your search included “MESH terms?
What was the evidence in focusing on elastography studies based on “Virtual Touch Quantification -VTQ systems”? What about other ARFI-based elastography methods and time-harmonic elastography. If the focus is on VTQ-systems only, the title and flow chart needs to be adapted, and more evidence for the specific analysis of the elastography methods needs to be mentioned. The use for VTQ remains unclear. Alternative methods provided strong evidence for the use in renal elastography.
The controversy of deep kidney and limitation in penetration depth ARFI based methods should be discussed in detail. Where is the limitation of depth in ARFI based methods? In contrast, what is the situation with time-harmonic elastography?
Discussion
A general comment. The citations of the statements in the discussion are insufficient. The following is given as an example:
Page 7, lines 187-196
Page 8, lines 221-224.
“In general, the only distinction in measures between 201 stage 5 CKD and the other stages is plausible.” Do mean VTQ analysis is only useful to detects andstage CKD (CKD stage 5)? What then is the advantage over the conventional b-mode?
Page 7, line 208: Please, specify “mild renal disease”. Which CKD stage?
Page 8, lines 210-218: Please, provide more information about the hypotheses of both opposing results.
Page 8, lines 234-237: If the EFSUMB statement is quoted, it must also be added where the value of renal elastography is. Is renal elastography recommended for the clinic (especially VTQ)? If not - why?
Why does the histopathology do not correlate with renal SWS?
Last paragraph: The cited study from Barr et al. provides a heavily weighted limitation.
The study by Barr et al provides a high level of evidence and argues heavily against the usability of renal ultrasound elastography based on the ARFI technique. Why should one nevertheless argue against it? This point should be clearly better elaborated.
Comparability between different USE manufacturers is difficult. I agree with this. However, the question is why the studies within the VTQ group, which are based on the same manufacturer, differ so much.
Limitations of your work?
Conclusion:
“Renal elastography remains a potential tool for monitoring the progression of CKD…” This statement is supported by your work.
The conclusion needs to be rephrased entirely.
References:
References 1 and 2: Some information needs to be added here.
Further references to support the statement in the discussion section need to be added (see my comment above).
Author Response
We would like to thank you for your valuable comments and suggestions. We tried to answer every raised comment, and we hope that all the changes that have been performed lead to a substantial improvement of the manuscript.
As follows we summarize all the comments of the reviewer with the answers provided by us. All the modifications in the text have been performed using “Track Changes” and can be easily followed up.
Responses to Reviewer 1
We would like to thank reviewer 1 for all the comments, and we hope we could answer appropriately to all raised concerns as follows:
General comment:
KSWS is an uncommon abbreviation. SWS is a stand should be used.
Title
Confusing. This work is focusing on VTQ. The results presented do allow an overall elastography conclusion.
Response: We changed the title as a response to the reviewer's concerns. It is true that the meta-analysis part could be performed only on VTQ studies (due to the higher number, compared to the other systems available), but because in the article we referred to all available elastography methods, we did not resume the title to VTQ
Abstract
Modifications according to the following comments.
Response: The abstract has been changed, according to the changes performed in the main text.
Introduction
The introduction should elaborate a little better on the need for quantitative imaging. For example, stating the sensitivity/specificity of conventional ultrasound imaging (including references) could emphasize this need.
Elastography is often compared to clinical palpation. However, the phrase “Elastography, a new ultrasound-based approach, can be used to gather more detailed information that integrates palpation within ultrasound imaging” remains confusing, since palpation is not really integrated. A technical background related to shear wave speed should be added to the manuscript.
Response: The technical background has been added to the text, and the paragraph referring to palpation has been deleted
„The advantage over serologic methods could be that the results can be obtained in real-time during a patient visit without the need to wait for laboratory findings.” This is not an advantage with clinical relevance. Laboratory results are available within 24 hours. Creatinine and proteinuria, the most relevant parameters are usually available within hours. The advantages should be better elaborated.
Response: The reviewer is perfectly right. Elastography can potentially bring an advantage in the assessment of CKD in addition to the lab assessments used currently for the diagnosis, and not to replace them. We hope that the additions performed do respond to the reviewer's comment and improve the desired message.
Methods:
Important methods such as time-harmonic elastography (THE) is entirely missing. One high-impact publication focusing on CKD should be referenced and discussed (doi: 10.1148/radiol.2019182574).
One of the renal elastography pioneers, Stock et al., might be added by citation (doi: 10.3233/CH-2011-1503 / 0.3233/CH-2010-1340)
Response: We thank the reviewer for the suggestions. THE has been introduced in the discussion section, while the reference to the paper by Stock et al. has been introduced in the table
What was the evidence in focusing on elastography studies based on “Virtual Touch Quantification -VTQ systems”? What about other ARFI-based elastography methods and time-harmonic elastography. If the focus is on VTQ-systems only, the title and flow chart need to be adapted, and more evidence for the specific analysis of the elastography methods needs to be mentioned. The use of VTQ remains unclear. Alternative methods provided strong evidence for the use in renal elastography.
Response: The comments of the reviewer are being taken into consideration, and a paragraph regarding time-harmonic elastography has been introduced. The focus of the meta-analysis is on VTQ, because of the increased number of studies available using this method. The other elastographic methods have been mentioned, however, a meta-analysis could not be performed, because of the limited number so far.
The controversy of deep kidney and limitation in penetration depth ARFI based methods should be discussed in detail. Where is the limitation of depth in ARFI based methods? In contrast, what is the situation with time-harmonic elastography?
Response: Thank you for the observation, the important issue regarding renal depth has been introduced in the text.
Discussion
A general comment. The citations of the statements in the discussion are insufficient. The following is given as an example:
Page 7, lines 187-196
Page 8, lines 221-224.
Response: The missing citations have been added.
“In general, the only distinction in measures between 201 stage 5 CKD and the other stages is plausible.” Do mean VTQ analysis is only useful to detects and stage CKD (CKD stage 5)? What then is the advantage over the conventional b-mode?
Response: Thank you for this important comment. We changed this paragraph, in order to state more clearly that VTQ is not suitable for differentiating between CKD stages.
Page 7, line 208: Please, specify “mild renal disease”. Which CKD stage?
Response: According to the reviewer comment the statement regarding mild CKD has been corrected and explained in both sections (Results and Discussion)
Page 8, lines 210-218: Please, provide more information about the hypotheses of both opposing results.
Response: The question regarding the different results in different studies (increase vs. decrease of kidney SWS in CKD patients) is intriguing, and we try to provide an explanation in the following paragraphs regarding histology and especially renal blood flow.
Page 8, lines 234-237: If the EFSUMB statement is quoted, it must also be added where the value of renal elastography is. Is renal elastography recommended for the clinic (especially VTQ)? If not - why?
Response: Thank you for the comment, the paragraph has been completely rephrased, and as suggested the current lack of recommendation from the EFSUMB guideline is mentioned.
Why does histopathology do not correlate with renal SWS?
Response: We would like to thank the reviewer for the valuable comment regarding histology, we added a potential explanation of the lack of correlation in the text.
Last paragraph: The cited study from Barr et al. provides a heavily weighted limitation.
The study by Barr et al provides a high level of evidence and argues heavily against the usability of renal ultrasound elastography based on the ARFI technique. Why should one nevertheless argue against it? This point should be clearly better elaborated.
Comparability between different USE manufacturers is difficult. I agree with this. However, the question is why the studies within the VTQ group, which are based on the same manufacturer, differ so much.
Limitations of your work?
Response: We added a paragraph regarding the limitation of performing a meta-analysis of renal elastography studies
Conclusion:
“Renal elastography remains a potential tool for monitoring the progression of CKD…” This statement is supported by your work.
The conclusion needs to be rephrased entirely.
Response: The conclusion has been rephrased as requested by the reviewer.
References:
References 1 and 2: Some information needs to be added here.
Further references to support the statement in the discussion section need to be added (see my comment above).
Response: We added the information.
Reviewer 2 Report
Thank you for inviting me to evaluate the review titled “Elastography in the assessment of chronic kidney disease: a systematic review and a meta-analysis”. It is an interesting paper, which summaries the current evidence of the role of Elastography in the assessment of chronic kidney disease. The information in this review is helpful to clinical communities. The paper is well arranged and the logic is clear. The cited literature is comprehensive and modern. The provided figure and tables are well composed and understandable. The quality of language of the manuscript is quite acceptable for me. So, I recommend to you that this manuscript should be accepted.
Author Response
We would like to thank you for your encouraging words and appreciation.
Reviewer 3 Report
The authors performed a systematic review and meta-analysis of published data on renal elastography. Non-invasive methods of diagnosis and monitoring of the progression of the chronic kidney disease seem to be an attractive alternative for the kidney biopsy.
I suggest a careful edition of the text.
- page 4, line 99: KSWV (not KSWS?)
- page 8, line 217: same as above
- page 7, line 198: lacking ";" before however
- page 8, line 226: unclear "2020 respectively 2021" (not 2020 and 2021?)
- page 8, line 243: should be "." instead of ","
- page 9, lines 270/271: would be better: informed consent was obtained from subjects involved in the studies included into the analysis
Author Response
We would like to thank you for your encouraging words and appreciation.
page 4, line 99: KSWV (not KSWS?)
page 8, line 217: same as above
page 7, line 198: lacking ";" before however
page 8, line 226: unclear "2020 respectively 2021" (not 2020 and 2021?)
page 8, line 243: should be "." instead of ","
page 9, lines 270/271: would be better: informed consent was obtained from subjects involved in the studies included into the analysis
Response: Thank you for the observations, the changes have been performed.
