The diagnostic value of contrast-enhanced ultrasound (CEUS) as a new technique for imaging of vascular complications in renal transplants compared to standard imaging modalities

1 Introduction

Vascular complications are a common cause for hypertension and renal transplant dysfunction in renal transplant recipients. In the majority of cases transplant renal artery stenosis (TRAS) causes the transplant malfunction and it is strongly associated with an increased risk of subsequent renal graft failure [1]. Although the aetiology of TRAS is not completely understood, cytomegalovirus infection and delayed allograft function are considered risk factors [2]. The reported incidence of TRAS varies upon different studies between 1 and 23% [3]. In contrast, transplant renal vein thrombosis (TRVT) is less common than TRAS with a comparable high risk for graft loss. It is related to surgical complications with the venous anastomosis [4, 5]. Active bleeding may occur subsequent to renal allograft biopsy [5].

The imaging modality of choice if a transplant renal artery stenosis is suspected is the digital substraction angiography. This method offers an optimal diagnostic value and shows high technical success rates. An important advantage of this invasive imaging modality is the opportunity to perform a therapeutic angioplasty in the same session [6]. However, it has to be considered that this method requires iodine-based contrast agent, leads to radiation exposure and may cause complications like thromboembolism, arteriovenous fistulas or groin haematoma. Contrast-enhanced CT is non-invasive and offers the advantages of three-dimensional images and requires less contrast agent than DSA. Nevertheless, the administration of iodine-based contrast agent in patients with limited allograft function can be critical [7, 3]. A less commonly used technique to diagnose a suspected TRAS is radioisotope renography which shows high sensitivity but limited specificity [3]. In clinical routine basic ultrasound and colour-Doppler are the initial imaging modality of choice in most cases. Ultrasound is cost-effective, non-invasive and widely available and allows depicting vascularisation and parenchyma of the renal transplant [8, 9].

In relation to imaging of vascular complication CEUS has been shown to have a higher diagnostic value compared to standard ultrasound [10, 11]. Significant advantages of CEUS over the gold standard imaging modalities include the possibility to administer a contrast agent that shows no nephrotoxic or cardiotoxic effects and to perform the imaging as bedside examination [12–14].

This retrospective analysis study was performed to assess the sensitivity and specificity of CEUS in the diagnosis of vascular complications in renal transplant recipients compared to DSA, CT or radioisotope renography as gold standard imaging techniques.

2 Materials and methods

Between October 2006 and May 2017 a total of 33 renal transplant patients with elevated kidney function parameters underwent CEUS imaging and one imaging modality defined as gold standard (DSA, CT or radioisotope renography). In 17 (51.5%) cases DSA had been performed, 13 patients underwent contrast-enhanced CT and 3 radioisotope renographies were completed. CT, DSA and radioisotope renography imaging studies were performed with the protocols and imaging systems used at the time of the examination. CEUS imaging was performed using high-end ultrasound systems (GE Healthcare: LOGIQ E9; Philips Ultrasound iU22, EPIQ 7, Affiniti 70; Samsung: RS80A Prestige; Siemens Ultrasound: Sequoia, S2000, S3000) equipped with up-to date CEUS specific protocols available at the time of the examinations. The ultrasound probes used for CEUS included CA1-7A, C6-1 HD, C4-1 C5-1, and C 9-2Mhz probes available at the time of the examinations. To avoid unintentional early destruction of the microbubbles a low mechanical index (always <0.4) was used.

A second-generation blood pool contrast agent (SonoVue^®, Bracco, Milan, Italy) was used in all CEUS examinations. Using a peripheral 20–22G needle the contrast agent was administered as a bolus injection followed by a flush of 5 to 10 ml of 0.9% sodium chloride solution. 1.6 to 2.4 ml contrast agent was administered in a single examination in most cases, with a minimum of 1.0 ml and a maximum of 5.0 ml. A single dose of contrast agent was sufficient in the majority of cases, in individual cases the injection of contrast agent was repeated up to two times. The mean examination time ranged from 3 to 5 minutes. After the administration of SonoVue^® no critical adverse reaction was observed.

During the CEUS examination cine loops were acquired and stored in the picture archiving and communication system (PACS) of our institution. All imaging studies using CEUS, DSA, CT and radioisotope renography were performed successfully in all 33 patients. Imaging quality was satisfactory in all cases with no need to exclude patients from the study due to poor image quality. Imaging studies and patient record files of all patients were retrieved from the archiving system of our institution and imaging results were analysed retrospectively.

All CEUS examinations were performed and interpreted by a single experienced radiologist with more than 15 years of experience in CEUS.

Prior to each imaging examination oral and written consent of the patient was obtained. The local ethic committee approved the study protocol and study data were collected according to the principles of the Helsinki/Edinburgh Declaration of 2002. The authors followed the ethical guidelines for publication in Clinical Hemorheology and Microcirculation [15].

The 33 patients included in this study underwent renal transplantation between 1984 and 2016. Out of the 33 patients 17 (51.5%) were male and 16 patients (48.5%) were female. Mean age at the time of CEUS was 48.1 years ranging between 20.3 years and 73.5 years (SD±14.4 years). Mean period of time between renal transplantation and CEUS examination was 31.6 months (SD±76.5 months) and mean period of time between CEUS and DSA, CT or radioisotope renography was 15.3 days (SD±76.5 days). The underlying kidney diseases causing chronic renal failure were diabetic nephropathy, IgA nephropathy, polycystic kidney disease, granulomatosis with polyangiitis, Lupus nephritis, congenital reflux nephropathy, eclampsia or sepsis.

Diagnostic accuracy of CEUS was tested using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) compared to DSA, CT or radioisotope renography serving as gold standard.

3 Results

15 patients out of 33 patients showed vascular complications in gold standard imaging (DSA, CT or radioisotope renography). CEUS diagnosed the same vascular complications in these 15 patients. The diagnosed vascular complications were relevant transplant renal artery stenosis in 5 patients, arteriovenous fistula in 3 patients, pseudoaneurysm in 2 patients (Figs. 1–5), infarction, transplant vein thrombosis, haematoma, arterial dissection or venous compression of the renal allograft, 1 patient each. Standard imaging and CEUS showed no signs of vascular complications in 12 patients. In 6 cases a transplant renal artery stenosis was suspected in CEUS with no evidence of TRAS in the subsequent DSA.

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Fig.1

B-mode ultrasound in a renal transplant patient. The patient was referred from the nephrologists with a cyst-like lesion after renal transplantation (white arrows).

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Fig.2

Same patient as in Fig. 1. (a.) Colour-Doppler shows major vascularization inside this lesion mimicking a cyst suggestive of a pseudoaneurysm (yellow arrows). Interventional digital subtraction angiography was recommended for intervention and coiling of the pseudoaneurysm (b.) Digital subtraction angiography confirms the suggested diagnosis clearly showing a pseudoaneurysm after renal transplantation (yellow arrows). The pseudoaneurysm was occluded with coiling.

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Fig.3

Same patient as in Figs. 1 and 2. B-mode ultrasound after intervention now shows a hypoechoic area (white arrows). Additionally, interventional coils can be visualized (yellow arrow).

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Fig.4

Same patient as in Figs. 1–3. Colour-Doppler shows no major vascularization after coiling of the pseudoaneurysm (white arrows).

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Fig.5

Same patient as in Figs. 1–4. (a.) Contrast-enhanced ultrasound and (b.) digital subtraction angiography after coiling of the pseudoaneurysm. No blood flow can be visualized inside the former lumen of the pseudoaneurysm using both techniques (white arrows).

CEUS showed a sensitivity of 100%, a specificity of 66.7%, a positive predictive value (PPV) of 71.4% and a negative predictive value (NPV) of 100% in comparison to DSA, CT or radioisotope renography.

Vascular complications occur in less than 10% of renal transplantations. Dysfunction of the renal allograft caused by vascular complications is associated with high morbidity and mortality. The most common cause of vascular complications is the transplant renal artery stenosis, which occurs during the first 3 months after the transplantation in most cases [1, 4]. Other vascular complications such as transplant renal vein thrombosis, are quite rare in renal transplant recipients [4]. These complications are usually diagnosed with DSA, CT or less often using radioisotope renography [3]. Our study is in line with other studies showing the eligible diagnostic value of CEUS regarding depiction of cortical ischemia, infarctions and TRAS [10, 17]. Furthermore, arteriovenous fistulas and pseudoaneurysms, which are known complications of renal biopsies and usually not caused by the transplantation operation itself, can be diagnosed using CEUS [4, 18]. With this study we demonstrate the diagnostic value of CEUS regarding the diagnosis of more common and quite rare vascular complications after renal transplantation. CEUS depicted all 15 vascular complication diagnosed using gold standard imaging demonstrating the high sensitivity of this imaging modality. CEUS showed no false negative results, affording the performing radiologist to exclude vascular complications with high diagnostic certainty. In 6 cases the CEUS findings suggested a relevant transplant renal artery stenosis, which could not be depicted by subsequent DSA. Furthermore, the diagnostic value of CEUS is limited in cases of obesity and bowel gas formation. And examination results strongly depend on the skills and experience of the performing sonographer [3].

Even though there are cases where additional imaging is required for diagnosis of vascular complications our study shows a high sensitivity and negative predictive value of CEUS. This suggests that CEUS might help to reduce the number of administrations of nephrotoxic contrast agent in renal transplant recipients. As a non-nephrotoxic imaging method CEUS examinations can be repeated in short intervals, for example as therapy control subsequent to arterial angioplasty.

This study shows additional limiting factors regarding the study design: The study is designed as a retrospective, mono-centre analysis with only one experienced radiologist evaluating the vascular complications using CEUS imaging. During period of time different CEUS/DSA/CT/scintigraphy scanner, systems and protocols were used for the imaging studies of renal transplant patients in our institution.

5 Conclusion

CEUS is an eligible imaging modality to initially exclude vascular complications in renal transplant recipients. CEUS shows high sensitivity and NPV in the detection of vascular complications. In some cases additional imaging is still required for a certain diagnosis.