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Factors that Influence Kidney Shear Wave Speed Assessed by Acoustic Radiation Force Impulse Elastography in Patients without Kidney Pathology
Ultrasound in Med. & Biol., Vol. 41, No. 1, pp. 1–6, 2015 Copyright Ó 2015 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/$ - see front matter
http://dx.doi.org/10.1016/j.ultrasmedbio.2014.07.023
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Original Contribution FACTORS THAT INFLUENCE KIDNEY SHEAR WAVE SPEED ASSESSED BY ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY IN PATIENTS WITHOUT KIDNEY PATHOLOGY SIMONA BOTA,* FLAVIU BOB,y IOAN SPOREA,* ROXANA S¸IRLI,* and ALINA POPESCU* * Department of Gastroenterology and Hepatology, ‘‘Victor Babes¸’’ University of Medicine and Pharmacy, Timis¸oara, Romania; and y Department of Nephrology, ‘‘Victor Babes¸’’ University of Medicine and Pharmacy, Timis¸oara, Romania (Received 1 March 2014; revised 12 July 2014; in final form 31 July 2014)
Abstract—Our aim was to assess kidney shear wave speed by means of acoustic radiation force impulse (ARFI) elastography in patients without kidney pathology (‘‘normal’’ patients) and to identify the factors that influence it. We analyzed 91 ‘‘normal’’ patients in whom kidney shear wave speed was assessed by means of ARFI elastography. Five valid ARFI elastographic measurements were obtained in all ‘‘normal’’ patients in both kidneys. In univariate analysis, age (r 5 20.370, p 5 0.003), gender (female vs. male, r 5 20.305, p 5 0.003) and measurement depth (r 5 20.285, p 5 0.01) were significantly correlated with kidney shear wave speed values assessed by ARFI elastography, whereas body mass index, kidney length and renal parenchyma thickness were not correlated. In multivariate analysis, only age (p 5 0.006) and gender (p 5 0.03) were significantly correlated with kidney shear wave speed values. In conclusion, kidney shear wave speed values assessed by ARFI elastography in ‘‘normal’’ patients are influenced mainly by age and gender and less by measurement depth. (E-mail: flaviu_bob@yahoo. com) Ó 2015 World Federation for Ultrasound in Medicine & Biology. Key Words: Acoustic radiation force impulse, Acoustic radiation force impulse elastography, Kidney shear wave speed, ‘‘Normal’’ patients.
is quantified in a precise anatomic region, focused on a region of interest and displayed on the screen (Bamber et al. 2013). Little information is available regarding kidney shear wave speed evaluated by ARFI elastography in patients who have not undergone kidney transplantation (Gallotti et al. 2010; Guo et al. 2013), and no detailed analysis of the factors that influence kidney shear wave speed has been performed in a significant cohort of patients. The aims of our study were to assess kidney shear wave speed by means of ARFI elastography in ‘‘normal’’ patients and to identify the factors that influence it.
INTRODUCTION Acoustic radiation force impulse (ARFI) elastography is an ultrasound-based elastographic method used mainly in non-invasive assessment of liver fibrosis (Bota et al. 2013; Nierhoff et al. 2013), but also in evaluation of spleen stiffness, prediction of portal hypertension (Bota et al. 2012; Takuma et al. 2013) and assessment of thyroid nodules (Hou et al. 2013; Zhang et al. 2013), prostate lesions (Zhai et al. 2010) and focal liver lesions (Ying et al. 2012). Recently, this method was used also for assessment of kidney fibrosis, particularly in posttransplant patients (Grenier et al. 2013; Guo et al. 2013; He et al. 2014; Syversveen et al. 2012). This method is based on the shear wave speed in the organ being examined. The ultrasound probe automatically produces an acoustic ‘‘push’’ pulse that generates shear waves, which propagate into the tissue. Their speed
METHODS Patients Our prospective study included ‘‘normal’’ patients in whom kidney shear wave speed was evaluated by means of ARFI elastography between November 2012 and June 2013. The ‘‘normal’’ patients comprised healthy volunteers (medical students, nurses and medical doctors from our hospital) and patients hospitalized in various
Address correspondence to: Flaviu Bob, Department of Nephrology, ‘‘Victor Babes¸’’ University of Medicine and Pharmacy, 2 Chopin str., 300366 Timis¸oara, Romania. E-mail: flaviu_bob@yahoo. com 1
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departments of our hospital. Healthy volunteers did not have a history of kidney disease, arterial hypertension or diabetes mellitus, but additional tests were not performed. All healthy volunteers had normal renal ultrasonograms, and the difference in length between the right and left kidney was less than 15 mm. The patients hospitalized in various departments of our hospital were defined as patients without kidney pathology as they had no history of kidney disease and had normal biological tests (serum creatinine and blood urea nitrogen) and normal urinary tests (without proteinuria and hematuria) and did not have diabetes mellitus. In all these patients, renal ultrasonography was performed and the same criteria used for healthy patients were applied. All patients included in our study signed an informed consent; the study was approved by the local ethics committee and was in accordance with the Helsinki Declaration of 1975. Ultrasound examination The ultrasound examination was performed in each subject in the same session as the ARFI elastography measurements, using a Siemens Acuson S2000 ultrasound system (Siemens AG, Erlangen, Germany), with a 4- to 9-MHz convex array probe. Renal ultrasound was performed by one nephrologist (F.B.) with more than 10 y of experience in ultrasonography. All patients had normal kidney structure, which was defined as homogenous grainy gray renal parenchyma and bright renal sinus, without hydronephrosis, renal cysts, renal stones, tumors or pseudo-tumors. We also reported kidney length and renal parenchymal thickness. Kidney length was measured in a longitudinal section from the upper to the lower pole, whereas renal parenchymal thickness was measured in the midportion of the kidney opposite the renal hilum. ARFI elastography ARFI elastography was performed in all patients using Siemens Acuson S2000 ultrasound system software, Version 2.0, with a 4- to 9-MHz convex array probe using the Virtual Touch tissue quantification application. Scanning was performed with the patient in lateral decubitus. A region of interest cursor of pre-defined size (5 mm in width and 10 mm in length) was positioned by the operator in the midportion of the kidney, in the renal cortex, with minimal scanning pressure, while the patients were asked to stop breathing for a moment to minimize breathing motion (Fig. 1). We aimed for five valid measurements in each subject; from these, a median value was calculated, and the result expressed in meters per second (m/s). If the measurement was not valid, ‘‘x.xx’’ was displayed on the screen. Measurement depth is also displayed on the screen; the maximum depth at
Volume 41, Number 1, 2015
Fig. 1. Measurement of kidney shear wave speed with acoustic radiation force impulse elastography.
which ARFI elastography measurements can be performed is 8 cm. Statistical analysis Statistical analysis was performed using MedCalc Software, Version 12.4.0. (MedCalc Software, Ostend, Belgium). The distribution of the numerical variables was first tested with the Kolmogrov–Smirnov test. Either the mean value and standard deviation (normal distribution) or median value and range (non-normal distribution) are presented. Student’s t-test was used for group comparison of continuous variables with a normal distribution; otherwise, the Mann–Whitney U-test was applied. To compare qualitative variables, Pearson’s c2-test was used. Spearman’s rank correlation coefficient (r) was used to assess correlations between the results of kidney shear wave speed measurements made with ARFI elastography and such parameters as age, gender and kidney length. Backward stepwise multiple regression was used for multivariate analysis, which included only variables that reached statistical significance in univariate analysis. In this study, p-values ,0.05 were considered to indicate statistical significance. RESULTS Kidney shear wave speed was assessed by means of ARFI elastography in 91 ‘‘normal’’ patients. The main characteristics of these patients are summarized in Table 1. Five valid ARFI elastographic measurements were obtained in both kidneys of each ‘‘normal’’ patient. The mean kidney shear wave speed values obtained in the right and left kidneys were similar: 2.49 6 0.81 m/s versus 2.36 6 0.75, p 5 0.25. Because kidney shear wave speed values were similar for both kidneys, further
Kidney shear wave speed in the absence of pathology d S. BOTA et al.
Table 1. Characteristics of patients Age (y) Age 18–30 y 31–50 y 51–65 y .65 y Gender Male Female Body mass index (kg/m2) Type of ‘‘normal’’ patients Healthy volunteers Patients with normal renal tests Kidney length (mm) Right kidney Left kidney Renal parenchymal thickness (mm) Right kidney Left kidney Measurement depth (cm) Right kidney Left kidney Creatinine level (mg/dL)* Blood urea nitrogen (mg/dL)y
45.4 6 18.3 30 (32.9%) 19 (20.9%) 29 (31.9%) 13 (14.3%) 40 (43.9%) 51 (56.1%) 24.9 6 5.1 33 (36.3%) 58 (63.7%) 103.7 6 11.1 104.9 6 11.1 14.2 6 2.5 13.7 6 2.7 4.7 6 1.4 4.6 6 1.3 0.82 6 0.11 31.4 6 3.3
* Normal 5 0.7–1.3 mg/dL. y Normal 5 15–45 mg/dL.
analyses were made only for kidney shear wave speed values obtained in the right kidney. In univariate analysis, age, gender and measurement depth were significantly correlated (negative correlation) with kidney shear wave speed values assessed by ARFI elastography, whereas correlations of body mass index, kidney length and renal parenchymal thickness with kidney shear wave speed were not statistically significant (Table 2, Fig. 2). In multivariate analysis, only gender and age were correlated with kidney shear wave speed values (Table 3). Mean kidney shear wave speed values (m/s) assessed by ARFI elastography were significantly lower in men than in women: 2.22 6 0.76 versus 2.70 6 0.80, p 5 0.004. Mean kidney shear wave speed values (m/s) decreased with age: 18–30 y 5 2.94 6 0.60; 31– 50 y 5 2.26 6 0.82; 51–65 y 5 2.48 6 0.8; .5 y 5 1.82 6 0.63. Statistically significant differences in kidney shear wave speed values were observed between patients aged 18–30 y and the other patient cohorts and also between patients 51–65 y and those .65 y (Fig. 3). On analysis of the influence of gender on the different age groups, we observed that kidney shear wave speed values were significantly higher in women than in men in patients between 31–50 y and 51–65 y (Table 4). DISCUSSION In recent years, ultrasound-based elastographic methods have been proposed for kidney evaluation, espe-
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Table 2. Correlation of different parameters with kidney shear wave speed assessed by acoustic radiation force impulse elastography: univariate analysis Parameter
Spearman correlation coefficient, r
p-Value
Age (y) Gender (female vs. male) Measurement depth (cm) Renal parenchymal thickness (mm) Body mass index (kg/m2) Kidney length (mm)
20.370 20.305 20.285 20.151 20.127 0.026
0.0003 0.003 0.01 0.15 0.23 0.80
cially after kidney transplantation, but until now, few data have been published (Gallotti et al. 2010; Grenier et al. 2013; Guo et al. 2013; He et al. 2014; Syversveen et al. 2012). One of the methods proposed for evaluation of these patients is ARFI elastography, but prior to use in routine clinical practice for the evaluation of nontransplanted kidneys, the factors that influence kidney shear wave speed in ‘‘normal’’ patients must be evaluated. To interpret accurately the results obtained in patients with kidney pathology, knowledge of the increases or decreases with age, overweight and obesity and the influence of gender or measurement depth in normal patients is necessary. Until now, only one study (Guo et al. 2013) has tackled this issue, but the number of patients in this study for whom body mass index, kidney length and measurement depth were analyzed in detail was quite small (30 healthy volunteers); however, the influence of age and gender was studied in a larger cohort (327 patients). Also, the study by Guo et al. (2013) included only patients of Asian descent, and it is known that liver stiffness values assessed by ARFI elastography are lower in Asian versus European healthy volunteers and also in patient who suffer from chronic hepatitis C (Sporea et al. 2012). Our results indicate that kidney shear wave speed values are significantly correlated with age and gender in both univariate and multivariate analyses. Our results regarding the decrease in kidney shear wave speed values assessed by ARFI elastography with age are similar to the data published by Guo et al. (2013). Also, in the Chinese study (Guo et al. 2013), kidney shear wave speed values in patients with kidney disease decreased with impairment of renal function, so it seems that other factors, besides renal fibrosis, influence kidney shear wave speed. With respect to gender influence, no other data besides those presented in our study are available. We observed that kidney shear wave speed values are significantly lower in men than in women. Interestingly, when we considered different age groups, we observed that kidney shear wave speed values were significantly lower in men, only in patients aged 31–65 y, but it should be stated that the group of patients older than 65 y was quite small. We
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Volume 41, Number 1, 2015
Fig. 2. Analysis of correlation between kidney shear wave speed and (a) age, (b) gender, (c) measurement depth, (d) renal parenchymal thickness, (e) body mass index and (f) kidney length.
do not have an explanation for these findings, but it seems that kidney shear wave speed values obtained by ARFI elastography should be interpreted in the light of the age and gender of the patients. Table 3. Correlation of different parameters with kidney shear wave speed assessed by acoustic radiation force impulse elastography: Multivariate analysis Parameter
Coefficient
Standard error
p-Value
Age (y) Gender (female vs. male) Measurement depth (cm)
20.015 20.397 20.024
0.005 0.188 0.070
0.006 0.03 0.72
In opposition of the Guo et al. (2013) study, we observed that in univariate analysis, measurement depth significantly influenced kidney shear wave speed values, which decreased with measurement depth. This difference may be caused by the higher body mass index in our group of patients, so that more measurements were performed at greater depth. The decrease in kidney shear wave speed with depth observed in our study is in line with results published in studies performed on phantoms (Hall et al. 2013; Zhao et al. 2011) and with data observed in studies that analyzed the influence of depth on liver shear wave speed assessed by ARFI elastography in healthy volunteers (D’Onofrio et al. 2010; Kaminuma
Kidney shear wave speed in the absence of pathology d S. BOTA et al.
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of analysis of renal blood flow, which can influence renal elasticity according to published studies (Amador et al. 2010; Warner et al. 2011).
CONCLUSIONS Kidney shear wave speed values assessed by ARFI elastography in ‘‘normal’’ patients are influenced mainly by age and gender, with lower values being obtained in older patients and in men. Measurement depth also influences kidney shear wave speed values, but statistical significance was reached only in univariate analysis. Kidney length, renal parenchymal thickness and body mass index were not correlated with kidney shear wave speed values assessed by ARFI elastography. Fig. 3. Differences between kidney shear wave speed values assessed with acoustic radiation force impulse elastography in ‘‘normal’’ patients by age group.
et al. 2011). These results suggest that measurement depth should be reported for ARFI elastography; however, because the influence of measurement depth did not reach statistical significance in multivariate analysis in our study, this parameter may not be a very important factor influencing kidney shear wave speed values assessed by ARFI elastography. Future studies are needed to confirm our results. Similar to the study published by Guo et al. (2013), body mass index and kidney length were not correlated with kidney shear wave speed values. Additionally, we analyzed the influence of renal parenchymal thickness on kidney shear wave speed values assessed by ARFI elastography, but no significant correlation was obtained. Even though our study is the first to perform a detailed analysis of the factors that influence kidney shear wave speed values assessed by ARFI elastography in patients of European descent, it has some limitations: the inclusion of healthy volunteers without performing renal function tests, the unequal distribution of patients in the age groups (especially the relatively small number of patients .65 y, because it is more difficult to find patients with normal renal function at this age) and the lack Table 4. Influence of age on kidney shear wave speed values assessed by acoustic radiation force impulse elastography in different age groups Kidney shear wave speed (m/s) Age group 18–30 y 31–50 y 51–65 y .65 y
Men
Women
p-Value
3.04 6 0.50 (n 5 22) 1.92 6 0.72 (n 5 10) 2.19 6 0.73 (n 5 15) 1.77 6 0.37 (n 5 7)
2.90 6 0.64 (n 5 22) 2.64 6 0.79 (n 5 9) 2.79 6 0.83 (n 5 14) 1.87 6 0.27 (n 5 6)
0.59 0.04 0.04 0.79
REFERENCES Amador C, Urban MW, Kinnick R, Chen S, Greenleaf JF. Viscoelastic measurements on perfused and non-perfused swine renal cortex in vivo. In: Proceedings, IEEE International Ultrasonics Symposium, San Diego, California, USA, 11–14 October 2010. New York: IEEE; 2010. p. 1530–1533. Bamber J, Cosgrove D, Dietrich CF, Fromageau J, Bojunga J, Calliada F, Cantisani V, Correas JM, D’Onofrio M, Drakonaki EE, Fink M, Friedrich-Rust M, Gilja OH, Havre RF, Jenssen C, Klauser AS, Ohlinger R, Saftoiu A, Schaefer F, Sporea I, Piscaglia F. EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography: Part 1. Basic principles and technology. Ultraschall Med 2013;34:169–184. Bota S, Herkner H, Sporea I, Salzl P, Sirli R, Neghina AM, Peck-Radosavljevic M. Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver Int 2013;33:1138–1147. Bota S, Sporea I, Sirli R, Focsa M, Popescu A, Danila M, Strain M. Can ARFI elastography predict the presence of significant esophageal varices in newly diagnosed cirrhotic patients? Ann Hepatol 2012; 11:519–525. D’Onofrio M, Gallotti A, Mucelli RP. Tissue quantification with acoustic radiation force impulse imaging: Measurement repeatability and normal values in the healthy liver. AJR Am J Roentgenol 2010;195: 132–136. Gallotti A, D’Onofrio M, Pozzi Mucelli R. Acoustic radiation force impulse (ARFI) technique in ultrasound with Virtual Touch tissue quantification of the upper abdomen. Radiol Med 2010;115: 889–897. Grenier N, Gennisson JL, Cornelis F, Le Bras Y, Couzi L. Renal ultrasound elastography. Diagn Interv Imaging 2013;94:545–550. Guo LH, Xu HX, Fu HJ, Peng A, Zhang YF, Liu LN. Acoustic radiation force impulse imaging for non-invasive evaluation of renal parenchyma elasticity: Preliminary findings. PLoS One 2013;8:e68925. Hall TJ, Milkowski A, Garra B, Carson P, Palmeri M, Nightingale K, Lynch T, Alturki A, Andre M, Audiere S, Bamber J, Barr R, Bercoff J, Bercoff J, Bernal M, Brum J, Chan HW, Chen S, Cohen-Bacrie C, Couade M, Daniels A, DeWall R, Dillman J, Ehman R, Franchi-Abella SF, Fromageau J, Gennisson JL, Henry JP, Ivancevich N, Kalin J, Kohn S, Kugel J, Lee K, Liu NL, Loupas T, Mazernik J, McAleavey S, Miette V, Metz S, Morel BM, Nelson T, Nordberg E, Oudry J, Padwal M, Rouze N, Samir A, Sandrin L, Schaccitti S, Schmitt C, Shamdasani V, Song P, Switalski P, Wang M, Wear K, Xie H, Zhao H. RSNA/ QIBA: Shear wave speed as a biomarker for liver fibrosis staging. In: Proceedings, 60th IEEE International Ultrasonics Symposium, Prague, Czech Republic, 21–25 July 2013. New York: IEEE; 2013. p. 397–400.
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He WY, Jin YJ, Wang WP, Li CL, Ji ZB, Yang C. Tissue elasticity quantification by acoustic radiation force impulse for the assessment of renal allograft function. Ultrasound Med Biol 2014;40:322–329. Hou XJ, Sun AX, Zhou XL, Ji Q, Wang HB, Wei H, Sun JW, Liu H. The application of Virtual Touch tissue quantification (VTQ) in diagnosis of thyroid lesions: A preliminary study. Eur J Radiol 2013; 82:797–801. Kaminuma C, Tsushima Y, Matsumoto N, Kurabayashi T, Taketomi-Takahashi A, Endo K. Reliable measurement procedure of virtual touch tissue quantification with acoustic radiation force impulse imaging. J Ultrasound Med 2011;30:745–751. Nierhoff J, Chavez Ortiz AA, Herrmann E, Zeuzem S, Friedrich-Rust M. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: A meta-analysis. Eur Radiol 2013;23: 3040–3053. Sporea I, Bota S, Peck-Radosavljevic M, Sirli R, Tanaka H, Iijima H, Badea R, Lupsor M, Fierbinteanu-Braticevici C, Petrisor A, Saito H, Ebinuma H, Friedrich-Rust M, Sarrazin C, Takahashi H, Ono N, Piscaglia F, Borghi A, D’Onofrio M, Gallotti A, Ferlitsch A, Popescu A, Danila M. Acoustic radiation force impulse elastography for fibrosis evaluation in patients with chronic hepatitis C: An international multicenter study. Eur J Radiol 2012;81: 4112–4118. Syversveen T, Midtvedt K, Berstad AE, Brabrand K, Strøm EH, Abildgaard A. Tissue elasticity estimated by acoustic radiation force
Volume 41, Number 1, 2015 impulse quantification depends on the applied transducer force: An experimental study in kidney transplant patients. Eur Radiol 2012; 22:2130–2137. Takuma Y, Nouso K, Morimoto Y, Tomokuni J, Sahara A, Toshikuni N, Takabatake H, Shimomura H, Doi A, Sakakibara I, Matsueda K, Yamamoto H. Measurement of spleen stiffness by acoustic radiation force impulse imaging identifies cirrhotic patients with esophageal varices. Gastroenterology 2013;144:92–101.e2. Warner L, Yin M, Glaser KJ, Woollard JA, Carrascal CA, Korsmo MJ, Crane JS, Ehman RL, Lerman LO. Noninvasive in vivo assessment of renal tissue elasticity during graded renal ischemia using MR elastography. Invest Radiol 2011;46:509–514. Ying L, Lin X, Xie ZL, Tang FY, Hu YP, Shi KQ. Clinical utility of acoustic radiation force impulse imaging for identification of malignant liver lesions: A meta-analysis. Eur Radiol 2012;22:2798–2805. Zhai L, Madden J, Foo WC, Mouraviev V, Polascik TJ, Palmeri ML, Nightingale KR. Characterizing stiffness of human prostates using acoustic radiation force. Ultrason Imaging 2010;32:201–213. Zhang B, Ma X, Wu N, Liu L, Liu X, Zhang J, Yang J, Niu T. Shear wave elastography for differentiation of benign and malignant thyroid nodules: A meta-analysis. J Ultrasound Med 2013;32:2163–2169. Zhao H, Song P, Urban MW, Kinnick RR, Yin M, Greenleaf JF, Chen S. Bias observed in time-offlight shear wave speed measurements using radiation force of a focused ultrasoundbeam. Ultrasound Med Biol 2011;370:1884–1892.
http://dx.doi.org/10.1016/j.ultrasmedbio.2014.07.023
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Original Contribution FACTORS THAT INFLUENCE KIDNEY SHEAR WAVE SPEED ASSESSED BY ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY IN PATIENTS WITHOUT KIDNEY PATHOLOGY SIMONA BOTA,* FLAVIU BOB,y IOAN SPOREA,* ROXANA S¸IRLI,* and ALINA POPESCU* * Department of Gastroenterology and Hepatology, ‘‘Victor Babes¸’’ University of Medicine and Pharmacy, Timis¸oara, Romania; and y Department of Nephrology, ‘‘Victor Babes¸’’ University of Medicine and Pharmacy, Timis¸oara, Romania (Received 1 March 2014; revised 12 July 2014; in final form 31 July 2014)
Abstract—Our aim was to assess kidney shear wave speed by means of acoustic radiation force impulse (ARFI) elastography in patients without kidney pathology (‘‘normal’’ patients) and to identify the factors that influence it. We analyzed 91 ‘‘normal’’ patients in whom kidney shear wave speed was assessed by means of ARFI elastography. Five valid ARFI elastographic measurements were obtained in all ‘‘normal’’ patients in both kidneys. In univariate analysis, age (r 5 20.370, p 5 0.003), gender (female vs. male, r 5 20.305, p 5 0.003) and measurement depth (r 5 20.285, p 5 0.01) were significantly correlated with kidney shear wave speed values assessed by ARFI elastography, whereas body mass index, kidney length and renal parenchyma thickness were not correlated. In multivariate analysis, only age (p 5 0.006) and gender (p 5 0.03) were significantly correlated with kidney shear wave speed values. In conclusion, kidney shear wave speed values assessed by ARFI elastography in ‘‘normal’’ patients are influenced mainly by age and gender and less by measurement depth. (E-mail: flaviu_bob@yahoo. com) Ó 2015 World Federation for Ultrasound in Medicine & Biology. Key Words: Acoustic radiation force impulse, Acoustic radiation force impulse elastography, Kidney shear wave speed, ‘‘Normal’’ patients.
is quantified in a precise anatomic region, focused on a region of interest and displayed on the screen (Bamber et al. 2013). Little information is available regarding kidney shear wave speed evaluated by ARFI elastography in patients who have not undergone kidney transplantation (Gallotti et al. 2010; Guo et al. 2013), and no detailed analysis of the factors that influence kidney shear wave speed has been performed in a significant cohort of patients. The aims of our study were to assess kidney shear wave speed by means of ARFI elastography in ‘‘normal’’ patients and to identify the factors that influence it.
INTRODUCTION Acoustic radiation force impulse (ARFI) elastography is an ultrasound-based elastographic method used mainly in non-invasive assessment of liver fibrosis (Bota et al. 2013; Nierhoff et al. 2013), but also in evaluation of spleen stiffness, prediction of portal hypertension (Bota et al. 2012; Takuma et al. 2013) and assessment of thyroid nodules (Hou et al. 2013; Zhang et al. 2013), prostate lesions (Zhai et al. 2010) and focal liver lesions (Ying et al. 2012). Recently, this method was used also for assessment of kidney fibrosis, particularly in posttransplant patients (Grenier et al. 2013; Guo et al. 2013; He et al. 2014; Syversveen et al. 2012). This method is based on the shear wave speed in the organ being examined. The ultrasound probe automatically produces an acoustic ‘‘push’’ pulse that generates shear waves, which propagate into the tissue. Their speed
METHODS Patients Our prospective study included ‘‘normal’’ patients in whom kidney shear wave speed was evaluated by means of ARFI elastography between November 2012 and June 2013. The ‘‘normal’’ patients comprised healthy volunteers (medical students, nurses and medical doctors from our hospital) and patients hospitalized in various
Address correspondence to: Flaviu Bob, Department of Nephrology, ‘‘Victor Babes¸’’ University of Medicine and Pharmacy, 2 Chopin str., 300366 Timis¸oara, Romania. E-mail: flaviu_bob@yahoo. com 1
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Ultrasound in Medicine and Biology
departments of our hospital. Healthy volunteers did not have a history of kidney disease, arterial hypertension or diabetes mellitus, but additional tests were not performed. All healthy volunteers had normal renal ultrasonograms, and the difference in length between the right and left kidney was less than 15 mm. The patients hospitalized in various departments of our hospital were defined as patients without kidney pathology as they had no history of kidney disease and had normal biological tests (serum creatinine and blood urea nitrogen) and normal urinary tests (without proteinuria and hematuria) and did not have diabetes mellitus. In all these patients, renal ultrasonography was performed and the same criteria used for healthy patients were applied. All patients included in our study signed an informed consent; the study was approved by the local ethics committee and was in accordance with the Helsinki Declaration of 1975. Ultrasound examination The ultrasound examination was performed in each subject in the same session as the ARFI elastography measurements, using a Siemens Acuson S2000 ultrasound system (Siemens AG, Erlangen, Germany), with a 4- to 9-MHz convex array probe. Renal ultrasound was performed by one nephrologist (F.B.) with more than 10 y of experience in ultrasonography. All patients had normal kidney structure, which was defined as homogenous grainy gray renal parenchyma and bright renal sinus, without hydronephrosis, renal cysts, renal stones, tumors or pseudo-tumors. We also reported kidney length and renal parenchymal thickness. Kidney length was measured in a longitudinal section from the upper to the lower pole, whereas renal parenchymal thickness was measured in the midportion of the kidney opposite the renal hilum. ARFI elastography ARFI elastography was performed in all patients using Siemens Acuson S2000 ultrasound system software, Version 2.0, with a 4- to 9-MHz convex array probe using the Virtual Touch tissue quantification application. Scanning was performed with the patient in lateral decubitus. A region of interest cursor of pre-defined size (5 mm in width and 10 mm in length) was positioned by the operator in the midportion of the kidney, in the renal cortex, with minimal scanning pressure, while the patients were asked to stop breathing for a moment to minimize breathing motion (Fig. 1). We aimed for five valid measurements in each subject; from these, a median value was calculated, and the result expressed in meters per second (m/s). If the measurement was not valid, ‘‘x.xx’’ was displayed on the screen. Measurement depth is also displayed on the screen; the maximum depth at
Volume 41, Number 1, 2015
Fig. 1. Measurement of kidney shear wave speed with acoustic radiation force impulse elastography.
which ARFI elastography measurements can be performed is 8 cm. Statistical analysis Statistical analysis was performed using MedCalc Software, Version 12.4.0. (MedCalc Software, Ostend, Belgium). The distribution of the numerical variables was first tested with the Kolmogrov–Smirnov test. Either the mean value and standard deviation (normal distribution) or median value and range (non-normal distribution) are presented. Student’s t-test was used for group comparison of continuous variables with a normal distribution; otherwise, the Mann–Whitney U-test was applied. To compare qualitative variables, Pearson’s c2-test was used. Spearman’s rank correlation coefficient (r) was used to assess correlations between the results of kidney shear wave speed measurements made with ARFI elastography and such parameters as age, gender and kidney length. Backward stepwise multiple regression was used for multivariate analysis, which included only variables that reached statistical significance in univariate analysis. In this study, p-values ,0.05 were considered to indicate statistical significance. RESULTS Kidney shear wave speed was assessed by means of ARFI elastography in 91 ‘‘normal’’ patients. The main characteristics of these patients are summarized in Table 1. Five valid ARFI elastographic measurements were obtained in both kidneys of each ‘‘normal’’ patient. The mean kidney shear wave speed values obtained in the right and left kidneys were similar: 2.49 6 0.81 m/s versus 2.36 6 0.75, p 5 0.25. Because kidney shear wave speed values were similar for both kidneys, further
Kidney shear wave speed in the absence of pathology d S. BOTA et al.
Table 1. Characteristics of patients Age (y) Age 18–30 y 31–50 y 51–65 y .65 y Gender Male Female Body mass index (kg/m2) Type of ‘‘normal’’ patients Healthy volunteers Patients with normal renal tests Kidney length (mm) Right kidney Left kidney Renal parenchymal thickness (mm) Right kidney Left kidney Measurement depth (cm) Right kidney Left kidney Creatinine level (mg/dL)* Blood urea nitrogen (mg/dL)y
45.4 6 18.3 30 (32.9%) 19 (20.9%) 29 (31.9%) 13 (14.3%) 40 (43.9%) 51 (56.1%) 24.9 6 5.1 33 (36.3%) 58 (63.7%) 103.7 6 11.1 104.9 6 11.1 14.2 6 2.5 13.7 6 2.7 4.7 6 1.4 4.6 6 1.3 0.82 6 0.11 31.4 6 3.3
* Normal 5 0.7–1.3 mg/dL. y Normal 5 15–45 mg/dL.
analyses were made only for kidney shear wave speed values obtained in the right kidney. In univariate analysis, age, gender and measurement depth were significantly correlated (negative correlation) with kidney shear wave speed values assessed by ARFI elastography, whereas correlations of body mass index, kidney length and renal parenchymal thickness with kidney shear wave speed were not statistically significant (Table 2, Fig. 2). In multivariate analysis, only gender and age were correlated with kidney shear wave speed values (Table 3). Mean kidney shear wave speed values (m/s) assessed by ARFI elastography were significantly lower in men than in women: 2.22 6 0.76 versus 2.70 6 0.80, p 5 0.004. Mean kidney shear wave speed values (m/s) decreased with age: 18–30 y 5 2.94 6 0.60; 31– 50 y 5 2.26 6 0.82; 51–65 y 5 2.48 6 0.8; .5 y 5 1.82 6 0.63. Statistically significant differences in kidney shear wave speed values were observed between patients aged 18–30 y and the other patient cohorts and also between patients 51–65 y and those .65 y (Fig. 3). On analysis of the influence of gender on the different age groups, we observed that kidney shear wave speed values were significantly higher in women than in men in patients between 31–50 y and 51–65 y (Table 4). DISCUSSION In recent years, ultrasound-based elastographic methods have been proposed for kidney evaluation, espe-
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Table 2. Correlation of different parameters with kidney shear wave speed assessed by acoustic radiation force impulse elastography: univariate analysis Parameter
Spearman correlation coefficient, r
p-Value
Age (y) Gender (female vs. male) Measurement depth (cm) Renal parenchymal thickness (mm) Body mass index (kg/m2) Kidney length (mm)
20.370 20.305 20.285 20.151 20.127 0.026
0.0003 0.003 0.01 0.15 0.23 0.80
cially after kidney transplantation, but until now, few data have been published (Gallotti et al. 2010; Grenier et al. 2013; Guo et al. 2013; He et al. 2014; Syversveen et al. 2012). One of the methods proposed for evaluation of these patients is ARFI elastography, but prior to use in routine clinical practice for the evaluation of nontransplanted kidneys, the factors that influence kidney shear wave speed in ‘‘normal’’ patients must be evaluated. To interpret accurately the results obtained in patients with kidney pathology, knowledge of the increases or decreases with age, overweight and obesity and the influence of gender or measurement depth in normal patients is necessary. Until now, only one study (Guo et al. 2013) has tackled this issue, but the number of patients in this study for whom body mass index, kidney length and measurement depth were analyzed in detail was quite small (30 healthy volunteers); however, the influence of age and gender was studied in a larger cohort (327 patients). Also, the study by Guo et al. (2013) included only patients of Asian descent, and it is known that liver stiffness values assessed by ARFI elastography are lower in Asian versus European healthy volunteers and also in patient who suffer from chronic hepatitis C (Sporea et al. 2012). Our results indicate that kidney shear wave speed values are significantly correlated with age and gender in both univariate and multivariate analyses. Our results regarding the decrease in kidney shear wave speed values assessed by ARFI elastography with age are similar to the data published by Guo et al. (2013). Also, in the Chinese study (Guo et al. 2013), kidney shear wave speed values in patients with kidney disease decreased with impairment of renal function, so it seems that other factors, besides renal fibrosis, influence kidney shear wave speed. With respect to gender influence, no other data besides those presented in our study are available. We observed that kidney shear wave speed values are significantly lower in men than in women. Interestingly, when we considered different age groups, we observed that kidney shear wave speed values were significantly lower in men, only in patients aged 31–65 y, but it should be stated that the group of patients older than 65 y was quite small. We
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Volume 41, Number 1, 2015
Fig. 2. Analysis of correlation between kidney shear wave speed and (a) age, (b) gender, (c) measurement depth, (d) renal parenchymal thickness, (e) body mass index and (f) kidney length.
do not have an explanation for these findings, but it seems that kidney shear wave speed values obtained by ARFI elastography should be interpreted in the light of the age and gender of the patients. Table 3. Correlation of different parameters with kidney shear wave speed assessed by acoustic radiation force impulse elastography: Multivariate analysis Parameter
Coefficient
Standard error
p-Value
Age (y) Gender (female vs. male) Measurement depth (cm)
20.015 20.397 20.024
0.005 0.188 0.070
0.006 0.03 0.72
In opposition of the Guo et al. (2013) study, we observed that in univariate analysis, measurement depth significantly influenced kidney shear wave speed values, which decreased with measurement depth. This difference may be caused by the higher body mass index in our group of patients, so that more measurements were performed at greater depth. The decrease in kidney shear wave speed with depth observed in our study is in line with results published in studies performed on phantoms (Hall et al. 2013; Zhao et al. 2011) and with data observed in studies that analyzed the influence of depth on liver shear wave speed assessed by ARFI elastography in healthy volunteers (D’Onofrio et al. 2010; Kaminuma
Kidney shear wave speed in the absence of pathology d S. BOTA et al.
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of analysis of renal blood flow, which can influence renal elasticity according to published studies (Amador et al. 2010; Warner et al. 2011).
CONCLUSIONS Kidney shear wave speed values assessed by ARFI elastography in ‘‘normal’’ patients are influenced mainly by age and gender, with lower values being obtained in older patients and in men. Measurement depth also influences kidney shear wave speed values, but statistical significance was reached only in univariate analysis. Kidney length, renal parenchymal thickness and body mass index were not correlated with kidney shear wave speed values assessed by ARFI elastography. Fig. 3. Differences between kidney shear wave speed values assessed with acoustic radiation force impulse elastography in ‘‘normal’’ patients by age group.
et al. 2011). These results suggest that measurement depth should be reported for ARFI elastography; however, because the influence of measurement depth did not reach statistical significance in multivariate analysis in our study, this parameter may not be a very important factor influencing kidney shear wave speed values assessed by ARFI elastography. Future studies are needed to confirm our results. Similar to the study published by Guo et al. (2013), body mass index and kidney length were not correlated with kidney shear wave speed values. Additionally, we analyzed the influence of renal parenchymal thickness on kidney shear wave speed values assessed by ARFI elastography, but no significant correlation was obtained. Even though our study is the first to perform a detailed analysis of the factors that influence kidney shear wave speed values assessed by ARFI elastography in patients of European descent, it has some limitations: the inclusion of healthy volunteers without performing renal function tests, the unequal distribution of patients in the age groups (especially the relatively small number of patients .65 y, because it is more difficult to find patients with normal renal function at this age) and the lack Table 4. Influence of age on kidney shear wave speed values assessed by acoustic radiation force impulse elastography in different age groups Kidney shear wave speed (m/s) Age group 18–30 y 31–50 y 51–65 y .65 y
Men
Women
p-Value
3.04 6 0.50 (n 5 22) 1.92 6 0.72 (n 5 10) 2.19 6 0.73 (n 5 15) 1.77 6 0.37 (n 5 7)
2.90 6 0.64 (n 5 22) 2.64 6 0.79 (n 5 9) 2.79 6 0.83 (n 5 14) 1.87 6 0.27 (n 5 6)
0.59 0.04 0.04 0.79
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