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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 1  |  Page : 60-65

Use of elastographic techniques as noninvasive tools in assessment of renal allograft fibrosis


1 Department of Internal Medicine, Faculty of Medicine, South Valley University, Qena, Egypt; Department of Internal Medicine, Arabian Gulf University (AGU), Manama, Bahrain
2 Department of Internal Medicine, Faculty of Medicine, South Valley University, Qena, Egypt
3 Department of Radiodignosis, Faculty of Medicine, South Valley University, Qena, Egypt
4 Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt

Date of Submission14-Sep-2019
Date of Decision15-Nov-2019
Date of Acceptance09-Dec-2019
Date of Web Publication26-Mar-2020

Correspondence Address:
Mohammed H Hassan
Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_125_19

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  Abstract 


Context Chronic allograft dysfunction is still the main cause of late allograft loss in kidney transplantation. Increased serum creatinine could be an indicator of progressive damage of the renal allograft and tubular atrophy and interstitial fibrosis, which need to be confirmed by the invasive, sometimes hazardous renal allograft biopsy.
Aims We aimed to assess the possibility of using transient elastography (fibroscan) either based on ultrasound or MRI as noninvasive tools for evaluation of renal allograft fibrosis and chronic allograft index (CAI).
Setting and design A prospective cohort study was conducted.
Patients and methods The study included 15 patients with renal allograft. Pelvi-abdominal sonar, renal Doppler, and fibroscan have been performed for the included patients. Serum urea and creatinine have been measured, and estimated glomerular filtration rate (eGFR) has been calculated for all patients. Renal biopsies were done in seven cases.
Statistical analysis Statistical package for the social sciences (version 13.0) was used for statistical analysis.
Results Stiffness was significantly correlated with interstitial fibrosis (P<0.05) and inversely related with eGFR (P<0.05). Stiffness values of patients with eGFR more than 50 ml/min were lower than those patients with eGFR less than 50 ml/min (P<0.05). Patients classed as CAI Banff grade 0 had significantly less parenchymal stiffness than patients with Banff grade 1 or grade 2 CAI (P<0.05). Stiffness values of patients have insignificant relationship between parenchymal stiffness and resistive index (P<0.225).
Conclusion Parenchymal renal allograft stiffness by TE is an effective method for identifying patients with CAI indicative for biopsy and modification of the immunosuppressive regimen.

Keywords: chronic allograft index, renal allograft, renal biopsy, renal fibrosis, transient elastography


How to cite this article:
Alsenbesy MA, Hashem AA, Abdelrazek GM, Hassan MH. Use of elastographic techniques as noninvasive tools in assessment of renal allograft fibrosis. Al-Azhar Assiut Med J 2020;18:60-5

How to cite this URL:
Alsenbesy MA, Hashem AA, Abdelrazek GM, Hassan MH. Use of elastographic techniques as noninvasive tools in assessment of renal allograft fibrosis. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Jul 10];18:60-5. Available from: http://www.azmj.eg.net/text.asp?2020/18/1/60/281347




  Introduction Top


Although renal transplantation is considered the golden treatment option for patients with end-stage renal dysfunction, allograft malfunction and dysfunction remain the main obstacles for the long-term survival of the kidney allograft and the patient himself. So early identification of the renal allograft damage helps proper management for prevention of further damage to the transplanted kidney [1],[2]. Although early identification of renal allograft injury remains difficult, renal biopsy with all its complications (including hemorrhage, perirenal hematoma, hematuria, and arteriovenous fistula) remains the golden tool for detection of renal allograft dysfunction [3]. Additionally, biopsies from renal allograft require adequate normal blood picture and coagulation profile, with strict bed rest being essential [4]. Thus, recent elastographic techniques either using ultrasound or MRI modalities are increasingly used as a noninvasive method for evaluation of renal allograft fibrosis [5].

Transient elastography (TE) is considered a noninvasive rapid method for tissue stiffness measurement [6]. It has been first confirmed as an excellent method to evaluate liver stiffness which was strongly correlated with the fibrotic stage of the liver in various liver diseases [7]. Independent of the stage of liver fibrosis, there are many other factors that affect the liver stiffness such as liver congestion, inflammation, or cholestasis [8],[9],[10]. TE also now has been applied on spleen and kidneys with insufficient data. Regarding the role of TE in the kidneys, it could assess the progression of fibrosis of the renal allograft and detect renal cortex stiffness changes and fibrosis prediction [11],[12],[13].

The present study aimed to assess and confirm the possibility of using TE as noninvasive tools for evaluation of renal allograft fibrosis and chronic allograft index (CAI).


  Patients and methods Top


Study design

A prospective cohort study has been conducted on 15 patients with renal allograft from both sexes. They were recruited from the Nephrology Unit of the Internal Medicine Department, Faculty of Medicine, South Valley University, after approval of the local university ethics committee and in accordance with the Declaration of Helsinki. An informed written consent has been obtained from every included patient.

Patients’ selection criteria

The included patients were with ages more than 18 years and should have stable allografts with no fluid accumulation around it and with renal parenchymal thickness more than 1 cm, and their serum creatinine levels should be less than 3 mg/dl. BMI should be less than 30 kg/m2 and skin allograft distance less than 3.5 cm to avoid any confounding factors [14].

Methodology

Full medical history and thorough clinical examination were done for the included patients. Serum urea, creatinine, renal Doppler, and Fibroscan (using Fibroscan touch 502 eCHOSens) were performed for all patients. Renal biopsies were done in seven included patients and classified according to Banff chronic changes in the interstitium as grade 0, grade 1, or grade 2.

Statistical analysis

Statistical package for social sciences software (version 13.0; SPSS Inc., Chicago, Illinois, USA) was used for data support and analysis. Data were normally distributed and are presented as numbers, percentages, means, and SDs. Pearson correlation was performed to measure the correlation between quantitative variables. P values were considered statistically significant at P value less than 0.05.


  Results Top


The current study has been conducted on 15 patients with renal allograft, comprising eight females and seven males. Their mean age was 38±11.45 years old, and the mean duration of kidney transplantation was 10±7.48 months. The mean values of serum creatinine, blood urea, and estimated glomerular filtration rate (eGFR) were 2.28±0.45, 121± 61.43 mg/dl, and 40.26±11.87 ml/min, respectively ([Table 1]).
Table 1 Demographic data of the included patients

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The sonographic findings of transplanted kidneys are summarized in [Table 2]. It was observed that the thickness of kidney cortex was normal in nine (60%) cases, thin in four (26.66%) cases, and thick in two (13.33%) cases. The corticomedullary differentiation was preserved in 11 (73.33%) cases and lost in four (26.66%) cases. The echogenicity of the grafts was normal in three (20%) patients, hyperechoic grade 1 in six (40%), hyperechoic grade 2 in three (20%), and hyperechoic grade 3 in three (20%), and finally, resistive index (RI) less than 0.7 was seen in two (13.33%) cases and more than 0.7 was found in 13 (86.66%) cases.
Table 2 Sonographic data of renal allografts

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Measurement of parenchymal stiffness was successful in 13 (86.6%) of 15 patients. Stiffness was positively correlated with interstitial fibrosis (r=0.66, P=0.001) ([Figure 1]a) and inversely related with eGFR (r=−0.46, P=0.003) ([Figure 1]b). Stiffness values of patients with eGFR more than 50 ml/min were lower than those patients with eGFR less than 50 ml/min (P<0.05).
Figure 1 Correlations of the renal parenchymal stiffness with both renal fibrosis (a) and eGFR (b). eGFR, estimated glomerular filtration rate.

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Patients classed as CAI Banff grade 0–1 had significantly less parenchymal stiffness than patients with Banff grade 2 CAI (P=0.007) ([Figure 2]). There is insignificant differences in parenchymal stiffness in terms of RI (P=0.225), thus parenchymal stiffness measured by TE reflects the interstitial fibrosis in renal allografts.
Figure 2 Parenchymal stiffness level in different chronic allograft index (CAI) Banff grades.

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Summary of the data of two cases among the seven patients who underwent renal biopsy is presented in [Figure 3] and [Figure 4].
Figure 3 A case of renal allograft since 6 years with serum creatinine=2.9 mg% and eGFR=19 ml/min. (a) Fibroscan score 41 pKa. (b) Gray-scale ultrasound shows grade II increase in echogenicity of the graft with cortical thickness=1.2 cm and longitudinal diameter=8 cm. (c) Doppler examination of the interlobar arteries shows RI=1.0. (d) Graft biopsy shows mild interstitial fibrosis and tubular atrophy according to Banff grade 3. eGFR, estimated glomerular filtration rate; RI, resistive index.

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Figure 4 A case of renal allograft since 4 years with s. creatinine=2.5 mg% and eGFR=22 ml/min. (a) Fibroscan score 32.9 pKa. (b) Gray-scale ultrasound shows grade I increase in echogenicity of the graft with cortical thickness=1.4 cm and longitudinal diameter=10 cm. (c) Doppler examination of interlobar arteries show RI=1.00. (d) Graft biopsy shows mild interstitial fibrosis and tubular atrophy according to Banff grade 1. eGFR, estimated glomerular filtration rate; RI, resistive index.

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  Discussion Top


In the revised Banff classification, the term chronic allograft nephropathy has been replaced by interstitial fibrosis and tubular atrophy [15]. Unfortunately the time between the beginning and progress of interstitial fibrosis and the rise in the serum creatinine is too long, thus at time of diagnosis depending on presence of elevated serum creatinine levels, there will be irreversible histopathological changes of the renal parenchyma have been already occurred [16]. Elastography provides data about the tissue elasticity, but is not considered as a routine tool for various renal disorders such as chronic kidney disease, renal failure, or allograft patients [17].

In the current study, we evaluate the use of TE (fibroscan) as a noninvasive technique for follow-up of the renal parenchymal stiffness before irreversible CAI occurs, which is the most common cause of graft failure after 1 year following renal transplantation. In our study, measurement of renal parenchymal stiffness was successful in 86.6% of the included cases, and our findings revealed significantly positive correlation between renal parenchymal stiffness and interstitial fibrosis and significantly positive correlation between renal parenchymal stiffness and eGFR, with nonsignificant correlation with the RI. These findings are in agreement with Arndt et al. [16], Lukenda et al. [18], and Nakao et al. [19], whereas other studies did not prove such correlations [20],[21].Additionally, our results showed significantly lower renal parenchymal stiffness in patients classed as CAI Banff grade 0-1 in comparison with those who have Banff grade 2, with insignificant difference in terms of RI. These findings were in agreement with Arndt et al. [16] and Grenier et al. [22].

Although TE cannot provide the diagnostic power of histopathological evaluation, its valuable role in monitoring and follow-up of the renal parenchymal stiffness may be beneficial to determine the patients who are indicated for renal biopsy.


  Conclusion Top


TE is a promising noninvasive tool for assessment of renal allograft fibrosis and superior to serum creatinine in early lesional detection. Additionally, it provides valuable data about CAI, helping to identify patient who will get benefit from renal biopsy or those require modification of immunosuppressive drug therapy.

Acknowledgements

The authors are thankful to all included patients for their cooperation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Torres A, Munoz R, Valdez-Ortiz C, Gonzalez-Parra E, Espinoza-Davila LE, Morales-Buenrostro R et al. Percutaneous renal biopsy of native kidneys: efficiency, safety and risk factors associated with major complications. Arch Med Sci 2011; 7:823–831.  Back to cited text no. 1
    
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Chapman JR, O’Connell PJ, Nankivell BJ. Chronic renal allograft dysfunction. J Am Soc Nephrol 2005; 16:3015–3026.  Back to cited text no. 2
    
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Nankivell BJ, Fenton-Lee CA, Kuypers DR, Cheung E, Allen RD, O’Connell PJ et al. Effect of histological damage on long-term kidney transplant outcome. Transplantation 2001; 71:515–523.  Back to cited text no. 3
    
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Mengel M, Chapman JR, Cosio FG, Cavaillé-Coll MW, Haller H, Halloran PF et al. Protocol biopsies in renal transplantation: insights into patient management and pathogenesis. Am J Transplant 2007; 7:512–517.  Back to cited text no. 5
    
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Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B et al. .Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51:454–462.  Back to cited text no. 8
    
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Ganne-Carrie N, Ziol M, de Ledinghen V, Douvin C, Marcellin P, Castera L et al. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 2006; 44:1511–1517.  Back to cited text no. 12
    
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Mueller S, Sandrin L. Liver stiffness. A novel parameter for the diagnosis of liver disease. Hepat Med 2011; 2:49–67.  Back to cited text no. 13
    
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Sommerer C, Scharf M, Seitz C, Millonig G, Seitz HK, Zeier M et al. Assessment of renal allograft fibrosis by transient elastography. Transplant Int 2013; 26:545–551.  Back to cited text no. 14
    
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Solez K, Colvin RB, Racusen LC, Sis B, Halloran PF, Birk PE et al. Banff ‘05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (‘CAN’). Am J Transplant 2007; 7:518–526.  Back to cited text no. 15
    
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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. Eur Soc Organ Transplant 2010; 23:871–877.  Back to cited text no. 16
    
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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; 46:1435–1440.  Back to cited text no. 18
    
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Nakao T, Ushigome H, Nakamura T, Harada S, Koshino K, Suzuki T et al. Evaluation of renal allograft fibrosis by transient elastography (Fibro Scan). Transplant Proc 2015; 47:640–643.  Back to cited text no. 19
    
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Syversveen T, Midtvedt K, Berstad AE, Brabrand K, Strom EH, Abildgaard A. Tissue elasticity estimated by acoustic radiation force impulse quantification depends on the applied transducer force: an experimental study in kidney transplant patients. Eur Radiol 2012; 22:2130–21137.  Back to cited text no. 20
    
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Asano K, Ogata A, Tanaka K, Ide Y, Sankoda A, Kawakita C et al. Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow? J Ultrasound Med 2014; 33:793–801.  Back to cited text no. 21
    
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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; 22:2138–2146.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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