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Zejun Ma1
, Shan Lu2
, Lexi Ding3
and Qiulun Lu4
*
1
Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, China
2
Department of Pharmacology, University of California, USA
3
Department of Ophthalmology, Xiangya Hospital, Center South University, China
4
Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, China
*Corresponding author: Qiulun Lu, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and
Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China
Submission: January 20, 2018; Published: March 29, 2018
Renal resistive index in mouse model
Review
Over decades, ultrasonography, reflecting the changes of
renal function and morphology, has been used in the assessment
of chronic kidney disease [1,2]. Besides detection of renal
macroscopic vascular abnormalities, ultrasonography could
identify changes in blood flow at the microvascular level [3,4,]. In
clinical application, evaluation of vascular impedance at different
sites of the renal parenchyma may indicate functional or structural
alterations within the kidneys, which provides useful diagnostic and
prognostic information [5]. Based on the Doppler ultrasonography,
the Resistive Index (RI), as a novel parameter calculated from the
blood flow velocities in vessels among the cardiac cycle, is used as
pulse-wave Doppler (PW-Mode) measurement of resistance and
compliance in downstream arteries [6]. Differences in RI reflect
downstream vasculature resistance, which could at least in part
depend on the degree of vascular compliance [7]. However, as
compliance increased, it became increasingly less dependent on
resistance. Despite of that, the higher index of RI, the higher is
velocity difference between the systole and the diastole [3].
In 1986, Rigsby et used RI values to evaluate acute rejection
after renal allografts [8]. In the following years, RI was considered
a reliable and repeatable renal function parameter in a variety of
clinical settings, such as detection and management of renal artery
stenosis [9], evaluation of progression risk in Chronic Kidney
Disease (CKD) [10], and differential diagnosis in acute and chronic
obstructive renal disease. Additionally, elevated Renal RI has been
shown to correlate with the degree of renal injury in hypertensive
patients [11]. Surprisingly, among those hypertensive patients,
RI analysis can also be considered as a complement predictor of
cardiovascular and renal outcomes [11].
Due to the repeatable and reliable RI analysis in clinics, renal
RI is gradually accepted in research studies with different animal
models. For example, RI could be useful in predicting the course
of acute renal failure in rabbits [12]; In rats, renal RI increased
significantly in the anheptic stage and decreased drastically after
the reperfusion in liver transplantation model [13]. Additionally,
there are publications reported that renal RI is associated with
renal impairment in mouse model. Westergren et al. [14] found the
increased renal RI in ob/ob mouse, the obese type 2 diabetic leptin-
deficient mouse, accompanying with the renal injury. Xu et al. [15]
also demonstrated that high fat diet induced the increase of renal RI
in mouse mode, with the increased ACR levels.
Renal RI is determined as following:
RI = (PSV – EDV) / PSV
PSV is peak systolic velocity, and EDV is End-Diastolic Velocity.
The blood flow is susceptible to instabilities of the environment
and operation procedure. There are multiple variables that affect
the blood flow involved in ultrasound measurement, such as
temperature, humidity, and et al. Also, blood flow could be affected
by the mouse status, including body temperature and the degree
of anesthesia. As what we concern, the method itself of blood flow
velocitymeasurementisnotpreciseandreliable. Itcouldbeaffected
by the position of mouse, the angles for blood flow measurement,
the site for measurement, and et al. Since the RI value is the ratio
of velocities, instead of absolute value, it is stable and unbiased
parameters for flow analysis.
Up till now, it was reported that there are two different types of
renalRI,knownasintrarenalRIandsuprarenalRI.Amongthosetwo
Review Article
1/3Copyright © All rights are reserved by Qiulun Lu
Volume 1 - Issue - 4
Abstract
Renal Resistive Index (RI) analysis by Doppler ultrasonography has been shown to be associated with renal injury in clinics. Additionally, renal RI
was applied on animals including rabbit, rat, and mouse in researches, which shows renal RI could also reflect the degree of renal impairment. There are
two different methods for renal RI analysis in mouse model currently. One of them is widely performed as intrarenal RI, while the other is suprarenal RI.
In this review, the difference of these two methods will discussed in depth, and their advantages and disadvantages will be described.
Keyword: Ultrasonography; Intrarenal RI; Suprarenal RI; Renal injury
Experimental Techniques in Urology & Nephrology
C CRIMSON PUBLISHERS
Wings to the Research
ISSN 2578-0395
Exp Tech Urol Nephrol Copyright © Qiulun Lu
2/3How to cite this article: Zejun Ma, Shan Lu, Lexi D, Qiulun Lu. Renal resistive index in mouse model. Exp Tech Urol Nephrol. 1(4). ETUN.000522.2018.
DOI: 10.31031/ETUN.2018.01.000522
Volume 1 - Issue - 4
available index, intra renal RI is widely accepted and used (Figure
1) [14]. The intrarenal RI is based on standard B mode examination
of the kidney to identify targeted intrarenal artery. This central
segmental artery, is identified with color-Doppler images of the
renal vascular tree. Subsequently, renal flow velocity was measured
using PW Doppler. On the other hand, suprarenal RI was performed
and described by Xu et al. [15]. After the probe was placed on the
mouse abdomen, transverse image of the suprarenal artery at the
level of the suprarenal gland were obtained. Then, the probe was
switched to the parasternal position to capture longitudinal images
of the abdominal aorta and left renal artery. Later, the suprarenal
artery was confirmed by the color Doppler. Once reaching the
right position, images of blood flow at the entrance of suprarenal
artery were taken via PW Doppler (Figure 2). Compare to intra
renal, suprarenal RI is more repeatable and comparable, as the site
of measurement is consistent. To be more specific, the entrance
of suprarenal artery is easier to find and appears to be consistent
in different mice, whereas intra renal RI has no solid standard
for identification. Moreover, Xu et al. [15] also demonstrated that
suprarenal RI is found to be associated with renal injury in high fat
diet-fed mice. In his study, suprarenal RI is positive correlated with
GFR at the early stage of high fat diet-induced renal injury. Even
though there are multiple advantages for suprarenal RI, it is still
necessary to include more experiments to validate its efficacy and
accuracy. Furthermore, whether suprarenal RI is also suitable for
rat and other animals are still understudied.
Figure 1 : Representative images for measurement of
intrarenal flow.
A: Typical image of kidney tissue was performed using
B mode. The intrarenal artery was marked in Green as
segmental intrarenal arteries.
B: The representative images of color Doppler was performed
to confirm the intrarenal arteries.
Figure 2 : Representative images for measurement of
suprarenal flow.
A: Typical image of abdominal artery was performed using
B mode. The suprarenal artery and abdominal artery were
marked in Green as segmental intrarenal arteries.
B: The representative images of color Doppler was performed
to confirm the entrance of suprarenal artery.
Acknowledgment
This study was supported by the grant from the National
Natural Science Foundation of China (81500720) and the grant
from Health Bureau Technology Fund of Tianjin (2014KZ092).
References
1.	 Tublin ME, Bude RO, Platt JF (2003) The resistive index in renal Doppler
sonography: where do we stand? American journal of roentgenology
180(4): 885-892.
2.	 Shakourirad A, Ataeefar M, Jozaghi S (2009) Assessment of the effect of
radio contrast media on resistive index of renal artery by color doppler
sonography. Saudi journal of kidney diseases and transplantation: an
official publication of the Saudi Center for Organ Transplantation, Saudi
Arabia 20: 91-6.
3.	 H Hosojima (2002) Intrarenal resistive index (RI) from renal duplex
Doppler sonography in type II diabetic patients with nephropathy. Nihon
rinsho. Japanese journal of clinical medicine 60 Suppl (8): 676-681.
4.	 Platt JF, Ellis JH, Rubin JM, DiPietro MA, Sedman AB (1990) Intra renal
arterial Doppler sonography in patients with nonobstructive renal
disease: correlation of resistive index with biopsy findings. AJR American
journal of Roentgenology 154(6): 1223-1227.
5.	 Kim ES, Kim HJ, Kim YJ, Lee SM, Lee HJ, et al. (2013) Resistive index as
a predictor of acute kidney injury caused by an angiotensin converting
enzyme inhibitor or angiotensin II receptor blocker in chronic kidney
disease patients. Kidney Res Clin Pract 32(4): 158-163.
6.	 Hosojima H (1998) Intrarenal Resistive Index (RI) from renal duplex
Doppler sonography in diabetic patients with nephropathy. Nihon
rinsho Japanese journal of clinical medicine 56Suppl (3): 505-509.
7.	 Krumme B, Hollenbeck M (2007) Doppler sonography in renal artery
stenosis--does the Resistive Index predict the success of intervention?.
Nephrology dialysis transplantation 22(3): 692-696.
3/3How to cite this article: Zejun Ma, Shan Lu, Lexi D, Qiulun Lu. Renal resistive index in mouse model. Exp Tech Urol Nephrol. 1(4). ETUN.000522.2018.
DOI: 10.31031/ETUN.2018.01.000522
Exp Tech Urol Nephrol Copyright © Qiulun Lu
Volume 1 - Issue - 4
8.	 Wan SK, Ferguson CJ, Cochlin DL, Evans C, Griffiths DF (1989) Duplex
Doppler ultrasound in the diagnosis of acute renal allograft rejection.
Clin Radiol 40(6): 573-576.
9.	 Radermacher J, A Chavan, J Bleck, A Vitzthum, B Stoess, et al. (2001) Use
of Doppler ultrasonography to predict the outcome of therapy for renal-
artery stenosis. N Engl J Med 344(6): 410-417.
10.	Radermacher J, Ellis S, HallerRenal H (2002) resistance index and
progression of renal disease. Hypertension 39(2pt 2): 699-703.
11.	 Doi Y, Iwashima Y, Yoshihara F, Kamide K, Hayashi S, et al. (2012) Renal
resistive index and cardiovascular and renal outcomes in essential
hypertension. Hypertension 60(3): 770-777.
12.	Yoon DY, Kim SH, Kim HD, Na DG, Goo JM, et al. (1995) Doppler
sonography in experimentally induced acute renal failure in rabbits.
Resistive index versus serum creatinine levels. Investigative radiology
30: 168-172.
13.	 Kong H Y, Chen F, He Y, Wu LJ, Wang LQ, et al. (2013) Intrarenal
resistance index for the assessment of acute renal injury in a rat liver
transplantation model. BMC nephrology 14: 55.
14.	 Westergren HU, Gronros J, Heinonen SE, Miliotis T, Jennbacken K, et al.
(2015)ImpairedCoronaryandRenalVascularFunctioninSpontaneously
Type 2 Diabetic Leptin-Deficient Mice. PloS one 10(6): e0130648.
15.	 Xu H, Ma Z, Lu S, Li R, Lyu L, et al. (2017) Renal Resistive Index as a Novel
Indicator for Renal Complications in High-Fat Diet-Fed Mice. Kidney
Blood Press Res 42(6): 1128-1140.
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Renal resistive index in mouse model: Asian Journal of Urology: Crimson Publishers

  • 1. Zejun Ma1 , Shan Lu2 , Lexi Ding3 and Qiulun Lu4 * 1 Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Medical University, China 2 Department of Pharmacology, University of California, USA 3 Department of Ophthalmology, Xiangya Hospital, Center South University, China 4 Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, China *Corresponding author: Qiulun Lu, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China Submission: January 20, 2018; Published: March 29, 2018 Renal resistive index in mouse model Review Over decades, ultrasonography, reflecting the changes of renal function and morphology, has been used in the assessment of chronic kidney disease [1,2]. Besides detection of renal macroscopic vascular abnormalities, ultrasonography could identify changes in blood flow at the microvascular level [3,4,]. In clinical application, evaluation of vascular impedance at different sites of the renal parenchyma may indicate functional or structural alterations within the kidneys, which provides useful diagnostic and prognostic information [5]. Based on the Doppler ultrasonography, the Resistive Index (RI), as a novel parameter calculated from the blood flow velocities in vessels among the cardiac cycle, is used as pulse-wave Doppler (PW-Mode) measurement of resistance and compliance in downstream arteries [6]. Differences in RI reflect downstream vasculature resistance, which could at least in part depend on the degree of vascular compliance [7]. However, as compliance increased, it became increasingly less dependent on resistance. Despite of that, the higher index of RI, the higher is velocity difference between the systole and the diastole [3]. In 1986, Rigsby et used RI values to evaluate acute rejection after renal allografts [8]. In the following years, RI was considered a reliable and repeatable renal function parameter in a variety of clinical settings, such as detection and management of renal artery stenosis [9], evaluation of progression risk in Chronic Kidney Disease (CKD) [10], and differential diagnosis in acute and chronic obstructive renal disease. Additionally, elevated Renal RI has been shown to correlate with the degree of renal injury in hypertensive patients [11]. Surprisingly, among those hypertensive patients, RI analysis can also be considered as a complement predictor of cardiovascular and renal outcomes [11]. Due to the repeatable and reliable RI analysis in clinics, renal RI is gradually accepted in research studies with different animal models. For example, RI could be useful in predicting the course of acute renal failure in rabbits [12]; In rats, renal RI increased significantly in the anheptic stage and decreased drastically after the reperfusion in liver transplantation model [13]. Additionally, there are publications reported that renal RI is associated with renal impairment in mouse model. Westergren et al. [14] found the increased renal RI in ob/ob mouse, the obese type 2 diabetic leptin- deficient mouse, accompanying with the renal injury. Xu et al. [15] also demonstrated that high fat diet induced the increase of renal RI in mouse mode, with the increased ACR levels. Renal RI is determined as following: RI = (PSV – EDV) / PSV PSV is peak systolic velocity, and EDV is End-Diastolic Velocity. The blood flow is susceptible to instabilities of the environment and operation procedure. There are multiple variables that affect the blood flow involved in ultrasound measurement, such as temperature, humidity, and et al. Also, blood flow could be affected by the mouse status, including body temperature and the degree of anesthesia. As what we concern, the method itself of blood flow velocitymeasurementisnotpreciseandreliable. Itcouldbeaffected by the position of mouse, the angles for blood flow measurement, the site for measurement, and et al. Since the RI value is the ratio of velocities, instead of absolute value, it is stable and unbiased parameters for flow analysis. Up till now, it was reported that there are two different types of renalRI,knownasintrarenalRIandsuprarenalRI.Amongthosetwo Review Article 1/3Copyright © All rights are reserved by Qiulun Lu Volume 1 - Issue - 4 Abstract Renal Resistive Index (RI) analysis by Doppler ultrasonography has been shown to be associated with renal injury in clinics. Additionally, renal RI was applied on animals including rabbit, rat, and mouse in researches, which shows renal RI could also reflect the degree of renal impairment. There are two different methods for renal RI analysis in mouse model currently. One of them is widely performed as intrarenal RI, while the other is suprarenal RI. In this review, the difference of these two methods will discussed in depth, and their advantages and disadvantages will be described. Keyword: Ultrasonography; Intrarenal RI; Suprarenal RI; Renal injury Experimental Techniques in Urology & Nephrology C CRIMSON PUBLISHERS Wings to the Research ISSN 2578-0395
  • 2. Exp Tech Urol Nephrol Copyright © Qiulun Lu 2/3How to cite this article: Zejun Ma, Shan Lu, Lexi D, Qiulun Lu. Renal resistive index in mouse model. Exp Tech Urol Nephrol. 1(4). ETUN.000522.2018. DOI: 10.31031/ETUN.2018.01.000522 Volume 1 - Issue - 4 available index, intra renal RI is widely accepted and used (Figure 1) [14]. The intrarenal RI is based on standard B mode examination of the kidney to identify targeted intrarenal artery. This central segmental artery, is identified with color-Doppler images of the renal vascular tree. Subsequently, renal flow velocity was measured using PW Doppler. On the other hand, suprarenal RI was performed and described by Xu et al. [15]. After the probe was placed on the mouse abdomen, transverse image of the suprarenal artery at the level of the suprarenal gland were obtained. Then, the probe was switched to the parasternal position to capture longitudinal images of the abdominal aorta and left renal artery. Later, the suprarenal artery was confirmed by the color Doppler. Once reaching the right position, images of blood flow at the entrance of suprarenal artery were taken via PW Doppler (Figure 2). Compare to intra renal, suprarenal RI is more repeatable and comparable, as the site of measurement is consistent. To be more specific, the entrance of suprarenal artery is easier to find and appears to be consistent in different mice, whereas intra renal RI has no solid standard for identification. Moreover, Xu et al. [15] also demonstrated that suprarenal RI is found to be associated with renal injury in high fat diet-fed mice. In his study, suprarenal RI is positive correlated with GFR at the early stage of high fat diet-induced renal injury. Even though there are multiple advantages for suprarenal RI, it is still necessary to include more experiments to validate its efficacy and accuracy. Furthermore, whether suprarenal RI is also suitable for rat and other animals are still understudied. Figure 1 : Representative images for measurement of intrarenal flow. A: Typical image of kidney tissue was performed using B mode. The intrarenal artery was marked in Green as segmental intrarenal arteries. B: The representative images of color Doppler was performed to confirm the intrarenal arteries. Figure 2 : Representative images for measurement of suprarenal flow. A: Typical image of abdominal artery was performed using B mode. The suprarenal artery and abdominal artery were marked in Green as segmental intrarenal arteries. B: The representative images of color Doppler was performed to confirm the entrance of suprarenal artery. Acknowledgment This study was supported by the grant from the National Natural Science Foundation of China (81500720) and the grant from Health Bureau Technology Fund of Tianjin (2014KZ092). References 1. Tublin ME, Bude RO, Platt JF (2003) The resistive index in renal Doppler sonography: where do we stand? American journal of roentgenology 180(4): 885-892. 2. Shakourirad A, Ataeefar M, Jozaghi S (2009) Assessment of the effect of radio contrast media on resistive index of renal artery by color doppler sonography. Saudi journal of kidney diseases and transplantation: an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 20: 91-6. 3. H Hosojima (2002) Intrarenal resistive index (RI) from renal duplex Doppler sonography in type II diabetic patients with nephropathy. Nihon rinsho. Japanese journal of clinical medicine 60 Suppl (8): 676-681. 4. Platt JF, Ellis JH, Rubin JM, DiPietro MA, Sedman AB (1990) Intra renal arterial Doppler sonography in patients with nonobstructive renal disease: correlation of resistive index with biopsy findings. AJR American journal of Roentgenology 154(6): 1223-1227. 5. Kim ES, Kim HJ, Kim YJ, Lee SM, Lee HJ, et al. (2013) Resistive index as a predictor of acute kidney injury caused by an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker in chronic kidney disease patients. Kidney Res Clin Pract 32(4): 158-163. 6. Hosojima H (1998) Intrarenal Resistive Index (RI) from renal duplex Doppler sonography in diabetic patients with nephropathy. Nihon rinsho Japanese journal of clinical medicine 56Suppl (3): 505-509. 7. Krumme B, Hollenbeck M (2007) Doppler sonography in renal artery stenosis--does the Resistive Index predict the success of intervention?. Nephrology dialysis transplantation 22(3): 692-696.
  • 3. 3/3How to cite this article: Zejun Ma, Shan Lu, Lexi D, Qiulun Lu. Renal resistive index in mouse model. Exp Tech Urol Nephrol. 1(4). ETUN.000522.2018. DOI: 10.31031/ETUN.2018.01.000522 Exp Tech Urol Nephrol Copyright © Qiulun Lu Volume 1 - Issue - 4 8. Wan SK, Ferguson CJ, Cochlin DL, Evans C, Griffiths DF (1989) Duplex Doppler ultrasound in the diagnosis of acute renal allograft rejection. Clin Radiol 40(6): 573-576. 9. Radermacher J, A Chavan, J Bleck, A Vitzthum, B Stoess, et al. (2001) Use of Doppler ultrasonography to predict the outcome of therapy for renal- artery stenosis. N Engl J Med 344(6): 410-417. 10. Radermacher J, Ellis S, HallerRenal H (2002) resistance index and progression of renal disease. Hypertension 39(2pt 2): 699-703. 11. Doi Y, Iwashima Y, Yoshihara F, Kamide K, Hayashi S, et al. (2012) Renal resistive index and cardiovascular and renal outcomes in essential hypertension. Hypertension 60(3): 770-777. 12. Yoon DY, Kim SH, Kim HD, Na DG, Goo JM, et al. (1995) Doppler sonography in experimentally induced acute renal failure in rabbits. Resistive index versus serum creatinine levels. Investigative radiology 30: 168-172. 13. Kong H Y, Chen F, He Y, Wu LJ, Wang LQ, et al. (2013) Intrarenal resistance index for the assessment of acute renal injury in a rat liver transplantation model. BMC nephrology 14: 55. 14. Westergren HU, Gronros J, Heinonen SE, Miliotis T, Jennbacken K, et al. (2015)ImpairedCoronaryandRenalVascularFunctioninSpontaneously Type 2 Diabetic Leptin-Deficient Mice. PloS one 10(6): e0130648. 15. Xu H, Ma Z, Lu S, Li R, Lyu L, et al. (2017) Renal Resistive Index as a Novel Indicator for Renal Complications in High-Fat Diet-Fed Mice. Kidney Blood Press Res 42(6): 1128-1140. For possible submissions Click Here Submit Article Creative Commons Attribution 4.0 International License Experimental Techniques in Urology & Nephrology Benefits of Publishing with us • High-level peer review and editorial services • Freely accessible online immediately upon publication • Authors retain the copyright to their work • Licensing it under a Creative Commons license • Visibility through different online platforms