BACKGROUND: Renal transplant patients have a higher risk for malignancies of the renal transplant. In most cases suspected renal malignancies will be detected during the regular ultrasound follow-up and will require cross-sectional imaging to rule out a malignant aetiology. But it is well known that contrast agents for computed tomography or magnetic resonance imaging are critical in patients with limited renal function. OBJECTIVE: This study aims to compare the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and gold standard imaging modalities in characterizing suspected renal transplant malignancies in renal transplant patients. METHODS: A total of 22 renal transplant patients who underwent one or more CEUS examinations and at least one standard imaging modality (CT or MRI) between 2005 and 2017 were included. Patient ages ranged from 28.2 years to 74.6 (mean age 55.7 years; SD±13.0 years). CEUS of 22 patients was correlated with a standard imaging modality, CT (15 out of 22) or MRI (7 out of 22), serving as gold standard. RESULTS: CEUS showed a sensitivity of 100%, a specificity of 94.4%, a positive predictive value (PPV) of 80%, and a negative predictive value (NPV) of 100%. CONCLUSIONS: CEUS is an eligible method to help characterizing suspected renal malignancies in renal transplant patients compared to the well-established imaging modalities CT and MRI. As an imaging modality with no nephrotoxic effects CEUS can be used repeatedly even in patients with limited renal function.
Contrast-enhanced ultrasound; CEUS; CT; MRI; renal transplant; malignancy
Renal transplant patients need livelong follow up to monitor transplant function and to screen for malignancies. Due to the improved survival rates after renal transplantation malignancies become a greater threat to the intermediate- and long-term survival of renal transplant recipients [[
This retrospective analysis was performed to evaluate the sensitivity and specificity of CEUS in the characterization of suspected renal transplant malignancies in renal transplant patients in comparison to CT and MRI as gold standard imaging techniques.
Between July 2005 and May 2017 a total of 22 renal transplant patients with a single suspected renal transplant malignancy underwent imaging examinations of CEUS and CT or MRI in our institution. All 22 renal transplant patients underwent CEUS, on 15 patients (68%) additional CT imaging and on 7 patients (32%) additional MRI was performed. CT and MRI imaging studies were performed with scanning protocols and scanners used at the time of the examination. Prior to each CEUS,CT or MRI 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 fur publication in Clinical Hemorheology an Microcirculation [[
The CEUS examinations were performed using high-end ultrasound systems with up-to date CEUS specific examination protocols available at the time of the examination (GE Healthcare: LOGIQ E9; Philips Ultrasound HDI 5000, iU22, EPIQ 7, Affiniti; Samsung: RS80A 50 Prestige, RS80A Prestige; Siemens Ultrasound: Sequoia, S2000, S3000). The ultrasound probes used included CA1-7A, C6-1 HD, C5-1, C4-1 and V4-1 probes available at the time of the examinations. All CEUS examinations were performed and interpreted by a single experienced radiologist with more than 15 years of experience in CEUS. A low mechanical index (always < 0.4) was used for examination to avoid unintentional early destruction of microbubbles.
A second-generation blood pool contrast agent (SonoVue
After the injection of the contrast agent cine loops were acquired and stored in the picture archiving and communication system (PACS) of our institution. CEUS and CT or MRI imaging were successfully performed in all 22 patients with satisfactory diagnostic image quality. Thus, no patient had to be excluded from the study due to poor image quality. In all 22 patients either CT or MRI imaging was performed and the imaging studies of our institution were available in PACS for all patients. Imaging studies and patient record files of all patients were retrieved from the archiving system and imaging results were analysed retrospectively.
In all 22 patients included in this study a suspected renal malignancy had been detected in the renal transplant during routine follow-up ultrasound using B-mode and colour-Doppler. The 22 patients underwent renal transplantation of the examined renal transplant between 1984 and 2015. 15 patients (68%) were male and 7 patients (32%) were female. Mean age at the time of CEUS was 55.7 years ranging from 28.2 years to 74.6 years (SD±13.0 years). Mean period of time between renal transplantation and CEUS examination was 120.1 months (SD±113.5 months) and mean period of time between CEUS and CT or MRI was 6.2 months (SD±11.6 months). The underlying diseases causing renal failure and leading to the renal transplant were diabetic nephropathy, hypertensive nephropathy, IgA nephropathy, congenital reflux nephropathy, polycystic kidney disease, granulomatosis with polyangiitis and Lupus nephritis.
In all of the 22 patients a suspected renal malignancy in the renal transplant had been described during non-contrast-enhanced ultrasound as part of the regular follow-up examination. CT and MRI respectively described 22 lesions in the renal transplants of these patients with a singular lesion found in the renal transplant of every patient. CT and MRI respectively detected all 22 lesions described in prior routine ultrasound. 4 out of 22 lesions showed characteristics of a malignant lesion in CT or MRI suspicious of renal cell carcinoma. Imaging examples are shown in [NaN] to [NaN] .
For statistical analysis diagnostic accuracy of CEUS was tested using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in comparison to CT or MRI defined as gold standard.
All 22 lesions of the renal transplants described in CT or MRI could be detected using CEUS.
In comparison to CT or MRI, CEUS showed a sensitivity of 100%, a specificity of 94.4%, a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 100%.
CT or MRI described 4 lesions as highly suspicious of renal cell carcinoma, which could be confirmed in all cases by histopathology following partial or complete nephrectomy of the renal transplant. Histopathology revealed a papillary renal cell carcinoma in 3 cases and a clear cell carcinoma in1 case.
CT and MRI respectively could exclude a malignant aetiology in 18 patients and CEUS in 17 patients. In 1 case CEUS falsely identified a lesion as malignant which was evaluated as Bosniak 2 F lesion in cross-sectional imaging. Cross-sectional imaging and CEUS concordantly identified the benign lesions as haemorrhagic or Bosniak 2 F cysts, haematoma, angiomyolipoma, pseudoaneurysms, inflammatory changes of the renal parenchyma or hypertrophic columns of Bertin.
Renal transplant recipients face an increased risk of developing malignant tumours. Studies have shown that renal malignancies are up to 15-fold more common in these patients compared to the general population [[
Limiting factors of this study are the retrospective mono-centre analysis with only one experienced radiologist evaluating the CEUS imaging results as well as varying amounts of CEUS contrast media administrations. During period of time different ultrasound and CT/MRI systems and scanner protocols were used for the imaging studies of renal transplant patients in our institution.
This study demonstrates a high sensitivity and specificity of CEUS in characterizing suspected renal transplant malignancies in renal transplant patients compared to CT and MRI as gold standard. Thus, these results are in line with several other studies regarding this topic and support the beneficial use of CEUS in renal transplant recipients.
Graph: Fig.1 B-mode ultrasound in a patient after renal transplantation. A hypoechoic lesion can be clearly visualized (white arrows).
Graph: Fig.2 Same patient as in Fig. 1. The hypoechoic mass (white arrows) shows vascularization inside the suspicious mass using color-doppler.
Graph: Fig.3 Same patient as in Figs. 1 and 2 Contrast-enhanced ultrasound shows an arterial perfusion of the suspicious renal mass with a relative hypoperfusion compared to the surrounding renal parenchyma (white arrows).
Graph: Fig.4 Same patient as in Figs. 1–3. Contrast-enhanced ultrasound shows a continuous hypoperfusion of the suspicious renal mass during the venous phase (white arrows) suspicious of a renal cell carcinoma.
Graph: Fig.5 Same patient as in Figs. 1–4. Contrast-enhanced ultrasound of the suspicious lesion shows a continuing hypoperfusion of the lesion during the late phase (white arrows) in line with sonographic features of a renal cell carcinoma. The result was later on histopathologically confirmed.
By K. Mueller-Peltzer; G. Negrão de Figueiredo; M. Fischereder; A. Habicht; J. Rübenthaler and D.-A. Clevert