Lal H, Ruidas S, Prasad R, Singh A, Prasad N, Kaul A, Bhadauria DS, Kushwaha RS, Patel MR, Jain M, Yadav P. Role of multi-parametric ultrasonography for the assessment and monitoring of functional status of renal allografts with histopathological correlation. World J Radiol 2024; 16(12): 782-793 [DOI: 10.4329/wjr.v16.i12.782]
Corresponding Author of This Article
Priyank Yadav, MCh, Assistant Professor, Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareli Road, Lucknow 226014, Uttar Pradesh, India. priyankmamc@gmail.com
Research Domain of This Article
Radiology, Nuclear Medicine & Medical Imaging
Article-Type of This Article
Prospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hira Lal, Surojit Ruidas, Raghunandan Prasad, Anuradha Singh, Department of Radiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Narayan Prasad, Anupma Kaul, Dharmendra S Bhadauria, Ravi S Kushwaha, Manas R Patel, Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Manoj Jain, Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Priyank Yadav, Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Author contributions: Lal H, Ruidas S, Prasad R, Bhadauria DS, Patel MR, Kaul A, and Kushwaha RS designed and coordinated the study; Lal H, Ruidas S, Prasad R, and Singh A performed the examinations, acquired and analyzed the data; Lal H, Ruidas S, and Singh A interpreted the data; Lal H, Ruidas S, and Yadav P wrote the manuscript; Lal H, Ruidas S, Prasad N, Yadav P, and Singh A performed the statistical analysis; All authors approved the final version of the article.
Institutional review board statement: The study was reviewed and approved by institutional review board of SGPGIMS, Lucknow, India (IEC code: 2019-14-MD-EXP-6/PGI/BE/159/2019; Date: 08.03.2019).
Clinical trial registration statement: No clinical trial registration was established for this study.
Informed consent statement: All study participants provided written consent prior to study enrollment.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
Data sharing statement: There are no additional data available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Priyank Yadav, MCh, Assistant Professor, Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareli Road, Lucknow 226014, Uttar Pradesh, India. priyankmamc@gmail.com
Received: May 27, 2024 Revised: November 3, 2024 Accepted: November 19, 2024 Published online: December 28, 2024 Processing time: 214 Days and 0.1 Hours
Abstract
BACKGROUND
The study focuses on the use of multi-parametric ultrasound [gray scale, color Doppler and shear wave elastography (SWE)] to differentiate stable renal allografts from acute graft dysfunction and to assess time-dependent changes in parenchymal stiffness, thereby assessing its use as an efficient monitoring tool for ongoing graft dysfunction. To date, biopsy is the gold standard for evaluation of acute graft dysfunction. However, because it is invasive, it carries certain risks and cannot be used for follow-up monitoring. SWE is a non-invasive imaging modality that identifies higher parenchymal stiffness values in cases of acute graft dysfunction compared to stable grafts.
AIM
To assess renal allograft parenchymal stiffness by SWE and to correlate its findings with functional status of the graft kidney.
METHODS
This prospective observational study included 71 renal allograft recipients. Multi-parametric ultrasound was performed on all patients, and biopsies were performed in cases of acute graft dysfunction. The study was performed for a period of 2 years at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, a tertiary care center in north India. Independent samples t-test was used to compare the means between two independent groups. Paired-samples t-test was used to test the change in mean value between baseline and follow-up observations.
RESULTS
Thirty-one patients had experienced acute graft dysfunction at least once, followed by recovery, but none of them had a history of chronic renal allograft injury. Mean baseline parenchymal stiffness in stable grafts and acute graft dysfunction were 30.21 + 2.03 kPa (3.17 + 0.11 m/s) and 31.07 + 2.88 kPa (3.22 + 0.15 m/s), respectively; however, these differences were not statistically significant (P = 0.305 and 0.252, respectively). There was a gradual decrease in SWE values during the first 3 postoperative months, followed by an increase in SWE values up to one-year post-transplantation. Patients with biopsy-confirmed graft dysfunction showed higher SWE values compared to those with a negative biopsy. However, receiver operating characteristic analysis failed to show statistically significant cut-off values to differentiate between the stable graft and acute graft dysfunction.
CONCLUSION
Acute graft dysfunction displays higher parenchymal stiffness values compared to stable grafts. Therefore, SWE may be useful in monitoring the functional status of allografts to predict any ongoing dysfunction.
Core Tip: This prospective study showed that mean shear wave elastography (SWE) and interlobar artery resistive index values were slightly higher in patients with acute graft dysfunction compared to stable grafts. Grafts with biopsy-confirmed dysfunction showed slightly higher values than biopsy negative grafts. Therefore, SWE may be a valuable imaging modality for the assessment of renal allograft pathology and their monitoring if combined with routine ultrasonography. Further evaluation on a larger more diverse sample cohort should be performed.
Citation: Lal H, Ruidas S, Prasad R, Singh A, Prasad N, Kaul A, Bhadauria DS, Kushwaha RS, Patel MR, Jain M, Yadav P. Role of multi-parametric ultrasonography for the assessment and monitoring of functional status of renal allografts with histopathological correlation. World J Radiol 2024; 16(12): 782-793
Renal transplantation is one of the greatest milestones of modern medicine with recipients anticipating 90%-95% graft survival[1]. Short-term graft survival has significantly increased owing to better immunosuppressive regimes[2]. However, acute graft dysfunction remains a concern. Therefore, patients are closely monitored during the early post-transplantation period. Graft function is usually assessed by serum creatinine/eGFR[3], urine analysis, and ultrasonography. In multi-parametric ultrasound, gray scale ultrasonography provides anatomical details. Color doppler shows vascular supply and hemodynamic status and shear wave elastography (SWE) evaluates renal parenchymal stiffness (tissue texture/density). Conventional gray scale ultrasound has limited sensitivity for detection of diffuse parenchymal diseases such as acute rejection. Color Doppler ultrasound is used to assess allograft vascular status. It provides resistive index (RI) and peak systolic velocity (PSV), which are important indicators of renal hemodynamics. However, serum markers usually lag behind the actual graft damage; i.e., they increase/decrease when a significant amount of graft damage has already occurred, sometimes irreversibly. In this scenario, a biopsy is considered the gold standard for diagnosis. Being an invasive procedure, biopsy carries some inherent risks like bleeding and infections. In addition, it has some limitations, including sampling error and interobserver variations[4]. Recently, ultrasound-based SWE, has emerged as a promising non-invasive alternative, measuring graft parenchymal stiffness, which is a surrogate marker of acute/chronic damage[5-12].
Elastography is an excellent non-invasive modality for evaluating tissue elasticity. Ultrasound can be used to generate shear waves in tissue. As sound waves propagate, a portion of their energy is transferred to the surrounding medium by absorption or reflection. The acoustic radiation force (F) imparted by ultrasound is given by the formula F = 2aIcL, where ‘a’ is the absorption coefficient, I is the temporal average intensity, and cL is the speed of sound. In diagnostic imaging, the magnitude of this force is negligible. However, by increasing the intensity of the sound waves, micron-level displacements can be achieved. The micron-level Shear Wave displacements induced by acoustic radiation force can be detected by the speckle tracking method. Because the speed of sound in tissue is approximately 1000 times faster than the shear wave speed, ultrasound can monitor the dynamics of shear wave propagation through tissue. Thus, ultrasound can provide both the stimulus to generate shear waves in tissue and the means to record the resulting tissue response, enabling SWE to be performed using a single diagnostic ultrasound probe. It is a low-cost, readily accessible, and portable imaging modality. SWE measurement can be acquired by ultrasound in seconds. These factors render SWE to be used in a variety of clinical settings. It is of potential use in the detection and dynamic monitoring of renal allograft pathology along with routine ultrasound. In this study, we evaluated the agreement between multi-parametric ultrasound and histopathology, focusing on the potential for SWE in the assessment of renal allograft during the early post-operative period.
MATERIALS AND METHODS
This was a prospective observational study conducted after approval from the institutional ethics committee (IEC code: 2019-14-MD-EXP-6/PGI/BE/159/2019; Date: March 08, 2019) for a period of 2 years (2019-2020) in the Department of Radiodiagnosis, in association with the Department of Nephrology and Pathology. The inclusion criteria were as follows: Age ≥ 18 years, patients presenting with acute graft dysfunction, patients beyond post-transplantation week one or at the time of discharge and patients with potential causes of graft dysfunction ruled out (renal artery stenosis/hydronephrosis/pyelonephritis). The exclusion criteria were: Graft with perigraft collection/hydronephrosis because they can adversely affect SWE values, grafts that underwent percutaneous nephrostomy and other interventional procedures leading to graft and perigraft fibrosis.
In this study, 91 patients were initially evaluated. However, 20 patients were subsequently excluded because they did not strictly adhere to inclusion criteria (4 patients) or presented with exclusion criteria (16 patients). Seventy-one renal transplant recipients were ultimately included and were followed up at regular intervals until 1 year of graft age. The first examination was performed 1-2 weeks after transplantation or at the time of discharge, and follow-up examinations were performed at the 4th week, 3rd month, 6th month and 12th month postoperatively (Figure 1). In addition, an examination was performed whenever a patient presented with graft dysfunction. Gray scale ultrasound, SWE, and Doppler were performed on all participants by two different radiologists blinded to each other’s results to avoid bias in evaluation. The first radiologist performed Gray scale and Doppler examination and the second radiologist performed SWE. Gray scale parameters of evaluation were size (length, width, thickness and volume), cortical thickness, cortical echogenicity, and cortico-medullary differentiation. Doppler parameters were measured at the ostium, hilum, and interlobar artery level. Six SWE readings were taken, two from each pole, and the mean value was considered for evaluation. Patients were categorized into two groups as follows: Stable allograft-eGFR ≥ 50 mL/min and stable serum creatinine on serial follow ups compared to previous routine evaluation or absolute value ≤ 1.5 mg/dL and negative or trace proteinuria and acute dysfunction- abrupt onset (few hours to 3 months) and eGFR < 50 mL/min OR absolute increase in serum creatinine of ≥ 0.3 mg/dL or percentage increase of ≥ 50% (1.5 times from baseline) OR proteinuria OR oliguria of < 0.5 mL/kg/hour for more than 6 hours.
Figure 1 Study population inclusion process.
BMI: Body mass index.
This study was performed with Aixplorer® Super Sonic Imagine (Aix-en-Provence, France) with XC6-1 (Single Crystal Curved) convex probe. Statistical analysis was performed using SPSS V26 (IBM Corp., Armonk, NY, United States). Independent samples t-test was used to compare the means between two independent groups. A paired-samples t-test was used to test the change in mean value between baseline and follow-up observations.
RESULTS
Demographic and baseline characteristics
The study population was comprised of 71 renal allograft recipients with a mean age of 31.68 ± 8.91 years, with males constituting the majority (93%) of the study cohort. At baseline, the mean serum creatinine was 1.27 ± 0.81 mg/dL, and the mean eGFR was 82.95 ± 32.65 mL/min/1.73 m². Throughout the study period, 31 patients experienced episodes of acute graft dysfunction, all of whom showed subsequent recovery. Importantly, none of the patients developed chronic renal allograft injury during the follow-up period. The detailed demographic and baseline clinical parameters are presented in Table 1.
Table 1 Distribution of demographic and baseline clinical values in study group (n = 71; male: 66, female: 5).
Variable data
Age
Ht
Wt
BMI
SBP
DBP
SCR
eGFR
Mean
31.68
1.64
54.58
20.34
154
97
1.27
82.95
Median
30.00
1.65
54.00
19.75
155
97
1.19
77.04
SD
8.91
0.07
9.02
3.13
19
12
0.81
32.65
Min
18
1.50
36
15.01
110
70
0.51
8.77
Max
55
1.82
77
27.28
196
130
7.28
188.52
Clinical parameters over time
Analysis of time-dependent changes in clinical parameters revealed significant variations in several key measurements. Systolic blood pressure, diastolic blood pressure, and eGFR demonstrated significant changes (P < 0.05) when baseline values were compared with subsequent follow-up measurements. However, serum creatinine levels remained relatively stable without significant temporal variations. When comparing patients with stable graft function to those with acute graft dysfunction, significant differences were observed in both serum creatinine and eGFR values, indicating clear biochemical distinctions between these groups.
Gray scale ultrasound parameters
Initial comparison of gray scale parameters between stable grafts and dysfunctional grafts revealed no statistically significant differences at baseline evaluation. However, temporal analysis demonstrated significant changes in multiple parameters over the follow-up period. The allograft showed progressive increases in size, including length, width, thickness, and overall volume. Similarly, cortical thickness demonstrated significant increase over time. Conversely, the skin-to-graft distance showed a significant decrease during the follow-up period, likely reflecting post-operative resolution of tissue edema.
SWE findings
Baseline SWE measurements revealed interesting patterns between the groups. In stable grafts, the mean value was 30.21 ± 2.03 kPa (range 26.32-37.48 kPa) with corresponding shear wave velocity of 3.17 ± 0.11 m/s (range 2.95-3.53 m/s). Patients with acute graft dysfunction showed slightly higher values of 31.07 ± 2.88 kPa (range 25.70-37.17 kPa) and 3.22 ± 0.15 m/s (range 2.90-3.53 m/s), although these differences did not reach statistical significance (P = 1.000; Table 2).
Table 2 Comparison of baseline kPa and m/s values of renal cortical stiffness among patients with stable graft function & patients with acute graft dysfunction.
Groups/variables
n
Mean
SD
95%CI
P value
Lower
Upper
kPa
Normal
57
30.21
2.03
29.67
30.74
0.305
Acute
14
31.07
2.88
29.41
32.73
M/S
Normal
57
3.17
0.11
3.14
3.19
0.252
Acute
14
3.22
0.15
3.13
3.31
The temporal evolution of SWE values showed a distinctive pattern throughout the post-transplantation period. Initial measurements at 1-2 weeks post-transplant yielded mean values of 30.24 ± 2.06 kPa and 3.17 ± 0.11 m/s. These values demonstrated a gradual decline over the following months, reaching 29.52 ± 2.14 kPa (3.12 ± 0.12 m/s) at one month and 29.04 ± 1.89 kPa (3.09 ± 0.10 m/s) at 3 months post-transplantation. Subsequently, a slight increase was observed, with values of 29.18 ± 1.76 kPa (3.11 ± 0.09 m/s) at 6 months and 29.29 ± 1.37 kPa (3.12 ± 0.08 m/s) at 1 year (Table 3). Notably, these later values remained below the initial baseline measurements throughout the first post-operative year.
Table 3 Change in the kPa and m/s values over time.
Time
Change in the kPa values over time
Change in the m/s values over time
Mean
SD
Median
P value
Mean
SD
Median
P value
Baseline
30.24
2.06
30.08
-
3.17
0.11
3.15
-
FU1
29.52
2.14
29.59
0.002
3.12
0.12
3.13
0.001
FU2
29.04
1.89
28.9
< 0.001
3.09
0.1
3.1
< 0.001
FU3
29.18
1.76
29.11
< 0.001
3.11
0.09
3.12
< 0.001
FU4
29.29
1.37
29.2
0.003
3.12
0.08
3.1
0.005
Doppler parameters
Doppler analysis revealed comparable RI measurements between groups at various anatomical locations. In patients with acute graft dysfunction, mean RI values were 0.75 ± 0.09 at the ostium, 0.70 ± 0.12 at the hilum, and 0.66 ± 0.10 at the interlobar artery level. Similar values were observed in patients with stable graft function, showing mean RI measurements of 0.73 ± 0.08, 0.71 ± 0.07, and 0.66 ± 0.07 at the respective locations. Both PSV and RI values showed a decreasing trend over time when compared with baseline measurements.
Correlation with biopsy findings
Among the patients who presented with acute allograft dysfunction, 14 demonstrated biopsy-confirmed pathology while 17 showed normal biopsy findings. Comparative analysis of imaging parameters between these subgroups revealed significantly higher SWE values in biopsy-proven cases during the second and third follow-up visits (Table 4). However, no significant differences were observed in interlobar artery RI values between the subgroups.
Table 4 Comparison of shear wave elastography and interlobar artery resistive index values between biopsy positive and biopsy negative acute graft dysfunction (within-group B).
Biopsy proven?
Young’s modulus in kPa
Shear wave velocity in m/s
ILA RI
No
Yes
No
Yes
No
Yes
Baseline
n
8
6
8
6
8
6
Mean
30.77
31.29
3.19
3.23
0.66
0.65
SD
3.43
2.62
0.19
0.13
0.13
0.09
P value
0.766
0.704
0.943
1st FU
n
6
2
6
2
6
2
Mean
30.70
30.81
3.19
3.20
0.61
0.67
SD
3.98
0.81
0.20
0.04
0.09
0.04
P value
0.951
0.948
0.229
2nd FU
n
9
2
9
2
9
2
Mean
28.50
33.27
3.06
3.32
0.66
0.62
SD
2.73
1.04
0.15
0.05
0.05
0.08
P value
0.010
0.006
0.646
3rd FU
n
5
4
5
4
5
4
Mean
28.06
31.64
3.06
3.24
0.63
0.68
SD
1.66
1.83
0.09
0.10
0.07
0.07
P value
0.022
0.037
0.391
4th FU
n
4
1
4
1
4
1
Mean
29.16
27.78
3.10
3.02
0.64
0.59
SD
0.51
-
0.04
-
0.05
-
P value
-
-
-
Statistical analysis
Linear regression analysis was performed to evaluate potential relationships between imaging and biochemical parameters. Using serum creatinine and eGFR as independent variables and SWE and RI values as dependent variables, we did not identify any significant correlations (Figures 2 and 3). Receiver operator curve analysis for predicting graft dysfunction revealed statistical significance only for serum creatinine (P < 0.001), with a cut-off value of 1.42 showing 86% sensitivity and 93% specificity (area under the curve = 0.937; Figure 4). No statistically significant cut-off values were identified for ultrasound parameters, including SWE and intrarenal RI measurements.
Figure 4 Receiver operating characteristic analysis between acute graft dysfunction and stable grafts based on serum creatinine levels.
ROC: Receiver operating characteristic.
Histopathological analysis
Histopathological analysis of biopsy specimens revealed diverse underlying pathologies in cases of acute graft dysfunction. Acute tubular necrosis was the most common finding, present in 20% of cases (Figure 5), followed by acute cellular rejection in 13% of cases (Figure 6). Less frequent findings included antibody-mediated rejection (3%), calcineurin inhibitor (CNI) toxicity (3%) (Figure 7), IgA nephropathy (3%), and borderline cellular rejection with CNI toxicity (3%). Notably, 55% of biopsies had no significant abnormalities, reinforcing the complex nature of graft dysfunction assessment.
Figure 5 Quantitative elastography measurement at the interpolar region of a transplant kidney with acute allograft dysfunction due to acute tubular necrosis.
A: Gray scale image; B: Color-coded map elasticity values distribution on a scale of 0 to 80 kPa and corresponding gray scale image (mean value 350 kPa and 3.4 m/s); C: Histopathological section shows acute tubular injury with dilation of tubules (blue arrow) and flattening of tubular epithelial cells (orange arrow; × 100 original magnification, H&E stain, scale bar = 100 μm).
Figure 6 Quantitative elastography measurement at the interpolar region of a transplant kidney with acute allograft dysfunction due to acute cellular rejection.
A: Gray scale image; B: Color-coded map of elasticity value distribution on a scale of 0 to 80 kPa and corresponding gray scale image (mean value 346 kPa and 3.4 m/s); C: Histopathological section shows severe tubulitis (blue arrow) along with tubulo-interstitial inflammation (black arrow) and interstitial edema (white arrow) in a case of Acute T cell Mediated Cellular Rejection Banff Grade IB (× 100 original magnification, PAS stain, scale bar = 100 μm).
Figure 7 Quantitative elastography measurement at the interpolar region of a transplant kidney with acute allograft dysfunction due to calcineurin inhibitor toxicity.
A: Gray scale image; B: Color-coded map of elasticity value distribution on a scale of 0 to 80 kPa and corresponding gray scale image (mean value 331 kPa and 3.3 m/s); C: Histopathological section shows features of CNI toxicity in form of beaded nodular adventitial fibrosis (green arrow) from a case of renal allograft recipient (× 400 original magnification, PAS stain, scale bar = 200 μm).
DISCUSSION
The emerging role of multi-parametric ultrasound, particularly sonoelastography, in renal allograft assessment has gained significant attention over the past decade. While this technology shows promise in combination with traditional gray scale ultrasound and color Doppler imaging, current limitations include the lack of standardization criteria, international consensus guidelines, and established threshold values for diagnostic purposes. The integration of these imaging modalities potentially offers a comprehensive evaluation encompassing morphological, vascular, and functional aspects of renal allografts, which could ultimately reduce the need for invasive biopsies in clinical decision-making[5-21]. Our analysis revealed marginally elevated mean SWE values in allografts with acute graft dysfunction compared to stable allografts, though these differences did not achieve statistical significance. This finding both aligns with and contradicts previous studies with smaller sample sizes, highlighting the complex nature of tissue elasticity measurements in transplanted kidneys[5-21]. The temporal pattern of SWE measurements in our study showed peak values during initial examination, followed by a gradual decrease until the third post-operative month, with a slight increase through the 1-year mark. Notably, the 1-year SWE values remained below the immediate post-transplantation measurements, contrasting with previous studies[9] that identified steady increases throughout the first post-transplantation year. The complex interaction of factors influencing renal parenchymal stiffness helps explain these temporal variations. Multiple studies have demonstrated that renal hemodynamics, urinary pressure, post-operative edema within the capsulated graft kidney, and cold ischemia-induced changes significantly impact tissue stiffness during the early postoperative period[22-25]. Grenier et al[7] demonstrated that reduced renal blood flow significantly decreases shear wave velocity, indicating the substantial influence of hemodynamic pressure on parenchymal stiffness. This relationship is particularly relevant given our observation of elevated blood pressure during the early postoperative period, which gradually normalized over time. Ischemic injury, an inevitable consequence of transplant surgery[26], likely contributes to increased tissue stiffness through microstructural changes. Additional factors affecting early post-operative SWE values include elevated urinary pressure due to functional stenosis at the newly created vesico-ureteric junction and parenchymal edema, both of which increase tissue tension within the non-compliant renal capsule[25,27]. The subsequent gradual increase in stiffness values may reflect the development of interstitial fibrosis/tubular atrophy, which Khan et al[28] suggested inevitably occurs even under optimal transplant conditions due to cumulative micro-injuries. Regarding RI measurements, we did not identify any significant long-term changes during the one-year follow-up period, though interlobar artery RI values showed a significant decrease from baseline (0.66 ± 0.08) at 1 month (0.64 ± 0.08) and 3 months (0.64 ± 0.05) post-transplantation. This observation aligns with Naesens et al's findings[29] of stable RI values in functioning grafts within the first post-operative year. The initially elevated RI values likely reflect tissue compression, increased tension from hemodynamic and urinary pressure, post-operative edema, and cold ischemia effects, with potential additional influence from pulse pressure, beta-blocker use, and diuretic therapy[29]. Our finding that intrarenal RI values did not significantly differ between stable allografts (0.66 ± 0.07) and those with acute dysfunction (0.66 ± 0.10) is consistent with several studies[20,30,31]. However, other studies have observed significantly higher intrarenal RI in acute graft dysfunction[12,32]. This discrepancy may be attributed to improved medical management leading to rapid resolution of graft dysfunction, as well as the influence of various hemodynamic factors including cardiac rhythm, heart rate, pulse pressure, atherosclerosis[33], and age[29] on RI measurements. A significant finding of our study was the difference in SWE values during the second and third follow-up visits between patients with biopsy-confirmed graft dysfunction and those with negative biopsy results. This observation suggests potential utility in selecting patients for biopsy, though further research is needed before establishing definitive guidelines. The histopathological analysis revealed diverse underlying pathologies, with acute tubular necrosis (20%) and acute cellular rejection (13%) being the most common findings, while 55% of biopsies showed no significant abnormality. Our methodology focused on cortical SWE sampling, supported by previous studies[20,34] that demonstrated higher and more reliable cortical vs medullary/sinus measurements. This approach helps minimize the sampling bias that can occur with multiple acquisitions from the same location or high variability from different locations[14,6,7,35]. The integrated analysis of multiple ultrasound parameters may provide more comprehensive insights than individual measurements alone. While our study found that neither SWE nor RI values independently showed strong diagnostic performance for graft dysfunction, the combination of these parameters with conventional gray scale findings offers potential advantages. For instance, when elevated SWE values were observed alongside changes in cortical echogenicity and cortico-medullary differentiation, the diagnostic confidence for graft dysfunction increased, particularly in cases that were subsequently confirmed by biopsy. The temporal correlation between multiple parameters, such as the parallel trends in SWE values, blood pressure measurements, and early post-transplant RI values, suggests that these parameters may reflect different aspects of the same pathophysiological processes. However, the lack of strong statistical correlations between these parameters indicates that each measurement likely provides unique information about graft status. This underscores the importance of a multi-parametric approach in graft assessment, where different ultrasound parameters may complement each other to provide a more complete picture of graft health. Future studies should focus on developing scoring systems that incorporate multiple ultrasound parameters, potentially weighted based on their relative diagnostic value, to enhance the overall accuracy of non-invasive graft assessment and better guide clinical decision-making regarding the need for biopsy. Several limitations should be acknowledged in our study. The single-observer nature of SWE measurements precluded interobserver variability analysis. The predominantly male Indian cohort may limit generalizability to other populations. The absence of protocol biopsies prevented correlation analysis between histopathologic changes in normal grafts and SWE values. Additional limitations include the single-center design, relatively short study duration, exclusive focus on living donor allografts, and lack of donor characteristic analysis.
CONCLUSION
Allografts with acute graft dysfunction revealed higher parenchymal stiffness values compared to those with a stable graft in our study. Therefore, SWE may aid in monitoring the functional status of the graft and predict any ongoing dysfunction. To conclude, SWE may serve as a non-invasive & cost-effective imaging tool to evaluate and monitor the renal allografts affected by acute graft dysfunction throughout their lifespan and hence helpful in further management. Thus, SWE can be of paramount importance in the future if added to the regular follow-up imaging protocol of renal allograft along with gray scale and Doppler imaging as an integral part of multi-parametric ultrasonography.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: American Urology Association, No. 00883547.
Specialty type: Radiology, nuclear medicine and medical imaging
Country of origin: India
Peer-review report’s classification
Scientific Quality: Grade B, Grade C
Novelty: Grade B, Grade B
Creativity or Innovation: Grade B, Grade B
Scientific Significance: Grade C, Grade C
P-Reviewer: Wang XM S-Editor: Lin C L-Editor: Filipodia P-Editor: Zheng XM
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