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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 14  |  Issue : 1  |  Page : 53-56

Usefulness of real-time sonoelastography for assessment of renal allograft fibrosis


1 Department of Urology, SMS Medical College, Jaipur, Rajasthan, India
2 Department of Nephrology, SMS Medical College, Jaipur, Rajasthan, India
3 Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
4 Department of Pathology, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission27-Sep-2019
Date of Acceptance25-Dec-2019
Date of Web Publication31-Mar-2020

Correspondence Address:
Dr. Shubham Agrawal
Department of Medicine, Mahatma Gandhi Medical College and Hospital, Sitapura, Jaipur - 302 022, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_53_19

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  Abstract 


Background: Currently, allograft renal biopsy is the only reliable tool available to detect fibrosis in the transplanted kidney. However, it is an invasive procedure and is associated with complications. Therefore, a noninvasive tool to detect renal allograft fibrosis is needed. Aims: The aim of the study was to evaluate the usefulness of real-time sonoelastography (RTS) in the diagnosis of renal allograft fibrosis. Subjects and Methods: We studied 15 renal allograft recipients who had chronic allograft nephropathy. RTS was performed by an experienced radiologist to semi-quantitatively determine cortical and medullary stain ratio. These parameters were compared with the degree of fibrosis as assessed by allograft renal biopsy. For comparison, patients were divided into two groups based on the degree of fibrosis: those with mild fibrosis (interstitial fibrosis and tubular atrophy [IFTA] <25%) and those with moderate-to-severe fibrosis (IFTA >25%). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of cortical strain ratio to discriminate between patients with mild fibrosis versus patients with moderate-to-severe fibrosis. Results: The mean cortical strain ratio was significantly higher in those who had mild fibrosis as compared to those who had moderate-to-severe fibrosis (2.46 ± 0.55 vs. 1.78 ± 0.15, P = 0.01), while the medullary strain ratio was comparable between the two groups. The diagnostic accuracy of cortical strain ratio, as evaluated by area under the curve of ROC analysis, was 0.96. Conclusion: RTS can differentiate between mild fibrosis and moderate-to-severe fibrosis with high accuracy.

Keywords: Allograft renal biopsy, chronic allograft nephropathy, cortical strain, elastography, interstitial fibrosis, renal transplant


How to cite this article:
Sahu RD, Jangid DK, Dhaker DS, Rathore V, Agrawal S, Yadav SS, Agrawal D, Joshi P. Usefulness of real-time sonoelastography for assessment of renal allograft fibrosis. Indian J Transplant 2020;14:53-6

How to cite this URL:
Sahu RD, Jangid DK, Dhaker DS, Rathore V, Agrawal S, Yadav SS, Agrawal D, Joshi P. Usefulness of real-time sonoelastography for assessment of renal allograft fibrosis. Indian J Transplant [serial online] 2020 [cited 2020 Jul 6];14:53-6. Available from: http://www.ijtonline.in/text.asp?2020/14/1/53/281770




  Introduction Top


Chronic allograft nephropathy remains the chief cause of late allograft failure among renal transplant recipients.[1] Chronic allograft nephropathy is characterized by interstitial fibrosis and tubular atrophy (IFTA). IFTA is the final outcome of various types of injury including acute and chronic rejections, hypoperfusion, ischemia-reperfusion injury, calcineurin toxicity, infection, and recurrent disease.[2] IFTA leads to progressive decline in renal function, which is typically detected by a rise in serum creatinine. However, rise in serum creatinine is a late and nonspecific marker of chronic allograft nephropathy.[3]

Allograft renal biopsy is the gold standard for the diagnosis of chronic allograft dysfunction, but it is associated with complications.[4] Its invasive nature, possibility of sampling error, and high cost make it an unviable tool for monitoring renal allograft.[5] Therefore, there is a need for noninvasive methods for the detection of early graft dysfunction.

Various noninvasive imaging modalities to detect interstitial fibrosis such as transient elastography,[6] acoustic radiation force impulse imaging,[7] and shear wave speed imaging[8] have been studied. While some studies have shown a good correlation between these methods and interstitial fibrosis, others have shown a poor correlation.[9] Recently, Gao et al. have demonstrated corticomedullary strain ratio obtained by the use of ultrasound elastic imaging to have a good correlation with grade of renal cortical fibrosis.[10] However, they have used offline analysis to analyze the deformation in the renal cortex and medulla to determine the strain ratios. The feasibility of using real-time sonoelastography (RTS) determined renal cortical strain to detect graft fibrosis was recently demonstrated by Weitzel et al.[11]

We report our experience with RTS to measure the cortical and medullary strain ratio of the kidney and its correlation with graft fibrosis.


  Subjects and Methods Top


Study center

The study was conducted in the Department of Nephrology, Sawai Man Singh Medical College, Jaipur, India. The center is a tertiary care teaching institute and provides a comprehensive management to patients with chronic kidney disease in the region, including renal transplant. About 50–100 renal transplants are done yearly in the center.

Study period

This study was conducted from December 2015 to December 2016.

Study subject

All renal allograft recipients who underwent renal biopsy for decreased graft function and whose renal biopsy was suggestive of chronic allograft nephropathy during the study were included in this study. Patients with transplant renal artery stenosis, large perinephric collections, hydronephrosis, and arteriovenous fistulas were excluded from the study. Demographic, clinical data, and investigation reports were recorded.

Real-time sonoelastography and estimation of renal transplant strain

During the study, 35 patients underwent renal allograft biopsies, of which 15 had IFTA. All patients underwent RTS before undergoing renal biopsy. An experienced radiologist (UJ) who was blinded to the clinical parameters of the patients performed RTS using HITACHI HI-VISION PREIRUS sonography machine with a linear (L-74M) 5–13 MHz transducer. The machine uses Elasto software program to document strain pattern and strain ratio.

Each patient was placed in the supine position and underwent a conventional sonographic examination, including grayscale. For RTS evaluation, after activating the elastography system of the machine, gentle compression and decompression pulses were applied over the transplanted kidney by the operator. The probe was placed perpendicular to the skin when applying pressure the compression force was such that the patient did not feel uneasiness during the compression. The ideal compression and decompression were confirmed by a regular sine wave on the velocity profile [Figure 1].
Figure 1: Real-time sonoelastography of allograft kidney. The right side of the frame shows color scale elastogram image, whereas the left side of the frame shows corresponding grayscale image. White arrow shows sinusoidal compression gradient. Black arrow depicts color scale used in elastogram with blue color indicating stiffer area. A depicts region of interest in the renal cortex, whereas B depicts region of interest in reference region. *Depicts the strain ratio calculated by the elastography system

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The images acquired during compression and decompression were displayed on the screen with gray scale on the left, and color scale elastography image superimposed on the corresponding gray scale on the right side of the screen [Figure 1]. Tissue stiffness in the color scale elastogram is depicted in a continuum of fundamental colors from red to blue, with blue indicating stiffer area (less strain) [Figure 1].

To calculate the cortical strain ratio, a region of interest (ROI) was placed in the cortex of the kidney and posterior abdominal wall (reference). Similarly, the medullary strain ratio was calculated by placing an ROI in the renal medulla and posterior abdominal wall. Both ROIs were of the same size to enable the areas to be compared and strain ratio was calculated. Strain ratio is the average strain in the reference area divided by the average strain in the targeted lesion and is automatically generated by the elastography software. To avoid strain decay, reference tissue was taken at the same depth as the lesion or with a difference in depth no more than 10 mm. For calculation of strain ratio, 5–6 images per patient were taken, and the image with optimum compression was chosen for further evaluation.

The ratios were calculated individually for upper pole, middle pole, and lower pole. The average of the three measurements was reported.

Kidney biopsy and histopathology

Kidney biopsies were performed under sonographic guidance by a trained nephrologist. Biopsies were evaluated based on the Banff 2007 classification of renal allograft pathology.[12]

The pathologist who evaluated the renal biopsies was unaware about the elastography findings. Patients were divided into two groups based on the degree of fibrosis on renal biopsies: those with mild fibrosis (IFTA <25%) and those with moderate-to-severe fibrosis (IFTA >25%).

Statistical analysis

The statistical analysis was performed using the SPSS software (version 20) (IBM Corp., Armonk, NY). Results were expressed as mean and standard deviation for continuous variables and values and percentages for categorical variables. Student's t-test was used to assess differences between the two groups. P < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curve analysis was performed to determine the best strain ratio cutoff value for identifying moderate-to-severe fibrosis.

Ethical clearance

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. The study has been approved by Institutional ethics committee of Sawai Man Singh Medical College and Attached Hospitals, Jaipur (IRB number 2182).


  Results Top


A total of 15 patients (13 men and 2 women) who have undergone living donor renal transplant had IFTA during the study. The mean age of the study population was 37.8 ± 10.1 years. Four (31.4%) patients had undergone unrelated living donor transplant. The mean ages of donors were 46.8 ± 6.9 years. The mean duration of transplant was 60.7 ± 38.8 months. The mean serum creatinine and estimated glomerular filtration rate (calculated by CKD-EPI equation) were 2.02 ± 1.04 mg/dl and 38.8 ± 20.3 ml/min, respectively [Table 1].
Table 1: Clinical characteristics and elastographic parameters of the study population

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Five (33%) patients had moderate-to-severe fibrosis as per the Banff classification. Age at transplant, donor age, duration of transplant, estimated glomerular filtration rate, and serum creatinine were comparable between those who had mild fibrosis and those who had moderate-to-severe fibrosis [Table 1].

While the mean medullary strain ratio was comparable between the two groups, the cortical strain ratio (2.46 ± 0.55 vs. 1.78 ± 0.15, P = 0.01) was significantly higher in those who had mild fibrosis [Table 1].

The ROC curve as a predictor of moderate-to-severe fibrosis is shown in [Figure 2]. The area under the curve for cortical strain ratio was 0.96. A cortical strain ratio cutoff of 1.97 was able to predict moderate-to-severe fibrosis with a sensitivity of 90% and specificity of 100%, while that of 1.87 was able to predict moderate fibrosis with a sensitivity of 90% and specificity of 80%.
Figure 2: Receiver operating characteristic curve for the cortical strain ratio as a predictor of moderate-to-severe fibrosis. The area under curve was 0.96

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  Discussion Top


Interstitial fibrosis is the end result of the various forms of injury affecting the renal allograft. Early detection of interstitial fibrosis is of paramount importance because progressive renal fibrosis can eventually lead to graft loss. Currently, surveillance biopsies remain the only reliable tool to detect early fibrosis in the graft.

The interstitial fibrosis is expected to change the elasticity properties of the renal allograft. Renal graft has good elasticity, but with fibrosis, it becomes less elastic. This change in elasticity can be measured by noninvasive elastography technique. However, a recent review on the use of elastography in the kidney found limited literature on its application in renal allograft.[13] Many of these studies evaluated sonographic techniques that are based on shear wave technology.[6],[7],[8],[14],[15] There are only a few studies on the use of RTS based on the method of strain imaging.[10],[16],[17],[18]

In the present study, the degree of fibrosis was reflected in terms of cortical strain ratio as patients with more than 25% fibrosis have significantly low cortical strain ratio. Our findings are consistent with the findings of Orlacchio et al.[16] In this study, they have used tissue mean elasticity (measured in arbitrary units), a parameter derived by postprocessing image evaluation to measure the elasticity of the allograft parenchyma. An inverse correlation between tissue mean elasticity and the degree of fibrosis was shown by the authors with the diagnostic accuracy of severe fibrosis as evaluated by area under the curve – ROC analysis similar to our study. Similar observation was made by Gao et al. who have used offline analysis using speckle-tracking software to derive cortical and medullary strain induced by external compression by the ultrasound transducer.[10]

Our finding is in contrast to Kahn et al. who have used strain ratio derived by RTS to measure the elasticity of the allograft parenchyma.[17] However, in this study, only 19 patients had undergone renal biopsy and only 3 (15.7%) had moderate-to-severe fibrosis. Authors themselves have concluded the statistically nonsignificant differences between the mild fibrosis and moderate-to-severe fibrosis group may be due to small sample size.

RTS being an operator-dependent technique is associated with high intra- and interobserver variability.[18] The variability may result from variation in pressure and speed of compression, image selection, and selection of ROI. It is also difficult to compare the results of different studies owing to the use of different methodologies (such as selection of ROI) and software used to measure strains. One of the major limitations of our study was we could not analyze intra- and interobserver reproducibility because all the elastographic observations were performed by a single operator. Another important limitation of our study was small sample size. Further, we did not analyze the effect of other parameters which could affect the elastographic findings such as acute rejection, glomerular inflammation, arteriosclerosis, urinary tract infections, and immunosuppressive therapies. Further studies with large sample size will be needed to address these issues.


  Conclusion Top


Despite these obvious limitations, our study has shown the strain ratio as measured by the RTS can differentiate between mild fibrosis and moderate-to-severe fibrosis with high accuracy. RTS may be used as a complementary imaging method during follow-up of renal allograft recipients. Further studies are needed to define the place of this noninvasive method of estimating fibrosis in renal allograft in the routine diagnostic algorithm.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: Have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 2004;4:1289-95.  Back to cited text no. 1
    
2.
Ganji MR, Harririan A. Chronic allograft dysfunction: Major contributing factors. Iran J Kidney Dis 2012;6:88-93.  Back to cited text no. 2
    
3.
Kaplan B, Schold J, Meier-Kriesche HU. Poor predictive value of serum creatinine for renal allograft loss. Am J Transplant 2003;3:1560-5.  Back to cited text no. 3
    
4.
Preda A, Van Dijk LC, Van Oostaijen JA, Pattynama PM. Complication rate and diagnostic yield of 515 consecutive ultrasound-guided biopsies of renal allografts and native kidneys using a 14-gauge Biopty gun. Eur Radiol 2003;13:527-30.  Back to cited text no. 4
    
5.
Schwarz A, Gwinner W, Hiss M, Radermacher J, Mengel M, Haller H. Safety and adequacy of renal transplant protocol biopsies. Am J Transplant 2005;5:1992-6.  Back to cited text no. 5
    
6.
Arndt R, Schmidt S, Loddenkemper C, Grünbaum M, Zidek W, van der Giet M, et al. Noninvasive evaluation of renal allograft fibrosis by transient elastography-a pilot study. Transpl Int 2010;23:871-7.  Back to cited text no. 6
    
7.
Stock KF, Klein BS, Cong MT, Regenbogen C, Kemmner S, Büttner M, et al. ARFI-based tissue elasticity quantification and kidney graft dysfunction:First clinical experiences. Clin Hemorheol Microcirc 2011;49:527-35.  Back to cited text no. 7
    
8.
Gennisson JL, Grenier N, Combe C, Tanter M. Supersonic shear wave elastography of in vivo pig kidney: Influence of blood pressure, urinary pressure and tissue anisotropy. Ultrasound Med Biol 2012;38:1559-67.  Back to cited text no. 8
    
9.
Syversveen T, Brabrand K, Midtvedt K, Strøm EH, Hartmann A, Jakobsen JA, et al. Assessment of renal allograft fibrosis by acoustic radiation force impulse quantification-a pilot study. Transpl Int 2011;24:100-5.  Back to cited text no. 9
    
10.
Gao J, Min R, Hamilton J, Weitzel W, Chen J, Juluru K, et al. Corticomedullary strain ratio: A quantitative marker for assessment of renal allograft cortical fibrosis. J Ultrasound Med 2013;32:1769-75.  Back to cited text no. 10
    
11.
Weitzel WF, Kim K, Rubin JM, Wiggins RC, Xie H, Chen X, et al. Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft nephropathy. Kidney Int 2004;65:733-6.  Back to cited text no. 11
    
12.
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: Updates and future directions. Am J Transplant 2008;8:753-60.  Back to cited text no. 12
    
13.
Duymuş M, Sait Menzilcioǧ lu M, Gök M, Avcu S. Kidney ultrasound elastography: Review. Kafkas J Med Sci 2016;6:121-9.  Back to cited text no. 13
    
14.
Grenier N, Poulain S, Lepreux S, Gennisson JL, Dallaudière B, Lebras Y, et al. Quantitative elastography of renal transplants using supersonic shear imaging: A pilot study. Eur Radiol 2012;22:2138-46.  Back to cited text no. 14
    
15.
Lukenda V, Mikolasevic I, Racki S, Jelic I, Stimac D, Orlic L. Transient elastography: A new noninvasive diagnostic tool for assessment of chronic allograft nephropathy. Int Urol Nephrol 2014;46:1435-40.  Back to cited text no. 15
    
16.
Orlacchio A, Chegai F, Del Giudice C, Anselmo A, Iaria G, Palmieri G, et al. Kidney transplant: Usefulness of real-time elastography (RTE) in the diagnosis of graft interstitial fibrosis. Ultrasound Med Biol 2014;40:2564-72.  Back to cited text no. 16
    
17.
Kahn J, Slowinski T, Thomas A, Filimonow S, Fischer T. TSI ultrasound elastography for the diagnosis of chronic allograft nephropathy in kidney transplanted patients. J Ultrason 2013;13:253-62.  Back to cited text no. 17
    
18.
Ozkan F, Yavuz YC, Inci MF, Altunoluk B, Ozcan N, Yuksel M, et al. Interobserver variability of ultrasound elastography in transplant kidneys: Correlations with clinical-Doppler parameters. Ultrasound Med Biol 2013;39:4-9.  Back to cited text no. 18
    


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