Three-dimensional contrast-enhanced magnetic resonance venography for detection of renal vein thrombosis: comparison with multidetector CT venography

Abstract

Background

Renal vein thrombosis is not uncommon, however, there have been few reports on the diagnostic accuracy of three-dimensional contrast-enhanced magnetic resonance venography (3D-CE-MRV) in the detection of renal vein thrombosis (RVT).

Purpose

To evaluate the value of 3D-CE-MRV for detecting RVT with multidetector computed tomography (CT) venography as reference standard.

Material and Methods

Thirty-two patients with nephrotic syndrome underwent renal CT venography and gradient echo pulse sequence (FLASH 3D) 3D-CE-MRV in a clinical 3-T whole-body MR scanner for suspected RVT with time interval of 0–5 days. RVT was recorded on a per-patient and per-vessel (left renal vein, right renal vein, and inferior vena cava) basis. The diagnostic accuracy of 3D-CE-MRV for detection of RVT was calculated with CT venography as reference standard. Inter-reader agreement for RVT detection was evaluated using Kappa statistics.

Results

Of 32 patients, CT venography detected 22 vessels with thrombosis in 17 patients, including five in right renal veins, 14 in left renal veins, and three in inferior vena cava, while 15 patients had no RVT. 3D-CE-MRV detected 21 vessels (21/96, 21.9%) with thrombosis in 16 patients (6/32, 50%), including five in right renal veins, 13 in left renal veins, and three in inferior vena cava, while 16 patients (16/32, 50%) had no RVT. With CT venography as reference standard, the sensitivities and specificities of 3D-CE-MRV for RVT detection were 94.1%, 100%; 95.5%, 100% on a per-patient and a per-vessel basis, respectively. Excellent inter-reader agreement (Kappa value = 0.969, P < 0.001) was observed for RVT detection.

Conclusion

3D-CE-MRV has a high diagnostic accuracy in the detection of RVT, which is optimal alternative imaging modality in the detection of RVT.

Keywords

Renal vein thrombosis computed tomography X-ray magnetic resonance imaging angiography

Introduction

Renal vein thrombosis (RVT), defined as the presence of thrombus in the major renal veins or their tributaries, is the most common venous thromboembolism complication in patients with nephrotic syndrome (1 –3). Incidence of RVT is estimated as 5∼62% in adults with nephrotic syndrome (1,4). Acute RVT typically presents with additional symptoms of ﬂank pain, hematuria, and proteinuria, and even kidney function failure. Although possibly without overt clinical symptoms, chronic RVT may act as a source of embolus causing symptoms primarily related to recurrent pulmonary emboli (5). Acute and chronic RVT and their associated pulmonary embolism are potentially life-threatening conditions (5). Thus, prompt diagnosis and treatment of RVT are very important, which can optimize the patient’s final outcome.

Imaging plays an important role in the detection and follow-up of RVT. In the last decade, multidetector computed tomography (CT) angiography/venography has been widely used in the diagnosis, presurgical planning, and follow-up of renovascular diseases with the replacement of conventional digital subtraction angiography (6 –8). CT venography (CTV) has been used to establish the diagnosis of RVT with nearly 100% sensitivity and specificity (1), but CT uses ionizing radiation and requires the administration of iodinated contrast agents, a potential risk in patients with impaired renal function. Thus, it is necessary to search alternative imaging modalities without radiation and iodinated contrast medium to establish the diagnosis of RVT. Magnetic resonance imaging (MRI) appears to be an optimal alternative to CT. No diagnostic performance study of MRI in the detection of RVT has been performed to the best of our knowledge, although some case reports can be found in the literature (9 –12). The purpose of this study was to evaluate the diagnostic performance of three-dimensional contrast-enhanced MR venography (3D-CE-MRV) at 3 T for RVT detection in a relatively large cohort including 32 patients with nephrotic syndrome with multidetector CTV as reference standard.

Material and Methods

Subjects

Our prospective study was approved by our local institutional review board; written informed consent was provided by patients or their parents. Thirty-two consecutive patients (21 men and 11 women; mean age, 40.2 ± 15.4 years; range, 17–70 years) underwent renal CTV and 3D-CE-MRV for evaluation of pulmonary embolism from December 2010 to March 2012. All patients were from our department of nephrology, one of the largest nephrology centers in China. Mean serum creatinine value were 1.05 ± 0.48 mg/dL and mean effective glomerular filtration rates were 112.50 ± 47.15 mL/min/1.73m². All patients were >16 years old, with the diagnosis of nephrotic syndrome (24-h urine protein >3.5 g; blood plasma albumins <30 g/L) and hypercoagulable state (hemoglobin >16 g/dl; prothrombin time <12 s; fibrinogen >400 mg/L; serum total cholesterol level ≥10 mmol/L); serum creatinine <2 mg/dl; and no contraindication to iodinated contrast material and MR examinations. The patients with interval duration of >5 days between CTV and 3D-CE-MRV were excluded from this study.

CT venography

All CT examinations were performed on a dual-source, dual-energy CT scanner (Somatom Definition, Siemens Medical Solutions, Forchheim, Germany). Renal CT venography was performed immediately after dual-energy CT pulmonary angiography, a routine CT protocol for screening venous thromboembolism in patients with nephrotic syndrome (13). Renal CT venography was obtained approximately 50–60 s after injection of a bolus of 70 mL iopromide (Ultravist; 300 mg I/mL, Bayer Schering Pharma, Berlin, Germany) followed by 30 mL saline solution into an antecubital vein via an 22-gauge catheter with injection rate 4.0 mL/s. Other parameters for renal CT venography were as follows: tube voltage, 120 kVp; effective tube current, 90 mAs; rotation time, 0.33 s; detector collimation, 64 × 0.6 mm; pitch, 1.4. Scanning time was 6–8 s. Automated tube current modulation was used in all CT studies (CAREDose 4D; Siemens Medical Solutions).

A group of radiologists with >10 years of experience in interpreting abdominal CT images first evaluated the presence or absence of thrombosis in the renal veins and inferior vena cava in CT report. One week after interpreting renal 3D-CE-MRV, one radiologist (LJZ, with 12 years of experience in interpreting abdominal CT images) reviewed all images on a commercial workstation (Syngo VE32E, Siemens Medical Solutions, Forchheim, Germany) including thin-slice (0.75 mm) axial enhanced CT images, coronal and curved reformatted images (2-mm slice thickness), who could adjust window level and width and reformatted in any dimensions to optimally visualize RVT. Image quality was rated as good (>250 HU), fair (150–250 HU), or poor (<150 HU) according to enhancement degree of renal veins (13). Good and fair image quality was regarded as appropriate for evaluation of RVT. The numbers and locations of thrombosis were recorded on a per-patient and per-vessel basis. Each patient was arbitrarily regarded as having three vessels: right and left renal veins and inferior vena cava. If a RVT extended into inferior vena cava, it was rated as contralateral RVT rather than inferior vena cava thrombosis. Acute RVT was defined as clear visualization of renal veins with non-enhanced filling defect, while chronic RVT as poor visualization of renal vein along with development of extensive collateral vessels around the kidney (14,15). If present, thrombosis in other abdominal veins was also recorded.

Three-dimensional contrast-enhanced MR venography

All MR exams were performed using a clinical 3-T whole-body MR scanner (Magnetom Trio, Siemens Medical Solutions, Erlangen, Germany) equipped with eight receiver channels and a gradient system with a maximum gradient strength of 40 mT/m and a slew rate of 200 T/m/s. For signal reception a combination of two spine array coils and a small flexible coil was used. Immediately after 20 mL of gadopentetate dimeglumine (Bayer HealthCare, Berlin, Germany) was injected through an antecubital vein with 2 mL/s injection rate for a high-resolution MR pulmonary angiography with a test bolus technique for determining optimal delay time, renal 3D-CE-MRV with a gradient echo pulse sequence (FLASH 3D) was followed, the delay time was approximately 50 s. Then, 20 mL of saline was injected via a 24-gauge catheter using an MR power injection system (Spectris Solaris EP MR Injection System, Medrad, Volkach, Germany). A high-resolution renal 3D-CE-MRV was then acquired with a gradient echo pulse sequence (FLASH 3D) using the following parameters: TE/TR, 2.7/1.0 ms; FA, 20°; receiver bandwidth, 620 Hz/pixel; acceleration factor, 3; FOV, 3564 × 380 mm; matrix, 256 × 256; slice thickness, 1.2 mm. The reconstructed voxel size was 0.9 × 0.8 × 1.2 mm. The total scan time for MRA was 18 s.

Image analysis of MRPA was performed by two radiologists (LJZ and CXT, with 12 and 2 years of experience in vascular MRI, respectively) who independently interpreted all renal 3D-CE-MRV (including contrast-enhanced axial images, coronal and curved reformatted images with slice thickness of 2 mm) at an image workstation (Leonardo console, Siemens AG, Medical Solutions, Forchheim, Germany). The two readers were blinded to CT results when interpreting renal 3D-CE-MRV. Readers were also asked to assess the image quality for renal 3D-CE-MRV and to subjectively record the image quality of MRPA as good (marked enhancement of renal veins and clear anatomy visualization), fair (moderate enhancement of renal veins and moderate anatomy visualization), or poor (poor enhancement of renal veins and poor anatomy visualization) according to enhancement degree of renal veins and anatomy visualization. Good and fair image quality was regarded as appropriate for evaluation of PE. Diagnostic evaluation (definition of RVT, methods for counting RVT and vessels) of RVT in renal 3D-CE-MRV was similar to that described for CT venography.

Statistical analysis

Statistical analysis was performed using the software SPSS version 16.0 (SPSS Inc. Chicago, IL, USA). Quantitative variables were expressed as mean ± SD, while categorical variables as frequency or percentage. With CT venography as reference standard, the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of renal 3D-CE-MRV for RVT detection were calculated on a per-patient and per-lobe basis, and 95% confidence intervals were calculated according to the efficient-score model. Kappa statistics were also calculated to quantify the inter-reader variability for the detection of RVT using CT venography and 3D-CE-MRV. Kappa values were interpreted as: <0.20, poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate; 0.61–0.80, good; and 0.81–1.00, very good agreement. P values <0.05 were regarded as statistically significant.

Results

Of 32 patients, image quality of CT venography was evaluated as good in 28 patients (87.5%, 28/32) and moderate in four patients (12.5%, 4/32). CT venography detected thrombosis in 22 vascular segments (22.9%, 22/96) in 17 patients (53.1%, 17/32) including five in right renal veins (Fig. 1), 14 in left renal veins (Fig. 2), and three in inferior vena cava (Fig. 3). Of 19 RVT, bilateral RVT was seen in three patients, right RVT in two patients, and left RVT in 11 patients. Three inferior vena cava thrombosis was solitary (n = 1), or was associated with right (n = 1) or left renal vein thrombosis (n = 1). Of all venous thrombosis, acute renal vein or inferior vena cava clots were seen in 12 patients, while chronic clots (Fig. 4) in five patients. In addition, CT venography detected left ovary vein thrombosis (Fig. 5) in one patient.

Fig. 1.

A 41-year-old man with nephrotic syndrome. (a) Curved reformatted CT image and (b) curved reformatted MR image show the filling defect (arrow) in the right renal vein extending into the inferior vena cava.

Fig. 2.

A 45-year-old woman with nephrotic syndrome. (a) Curved reformatted CT image and (b) curved reformatted MR image show the filling defect (arrow) in the left renal vein.

Fig. 3.

A 17-year-old boy with nephrotic syndrome. (a) Coronal reformatted CT image shows the filling defect in the inferior vena cava (arrow). (b) Coronal reformatted MR image also shows the filling defect in the inferior vena cava (arrow).

Fig. 4.

A 44-year-old man with nephrotic syndrome. (a) Coronal reformatted image shows the filling defect (arrow) in the left renal vein and collateral vessels around the left kidney. (b) Curved reformatted MR image shows the irregular left renal vein (arrow) and small collateral vessels around the left kidney. In this patient, negative finding was reported in the initial 3D-CE-MRV evaluation because no obvious filling defect was shown.

Fig. 5.

A 70-year-old woman with nephrotic syndrome. (a) Coronal reformatted image and (b) coronal maximum intensity projection image show the filling defects (arrow) in the left ovary vein. (c) Contrast-enhanced axial MR image shows the filling defect (arrow) in the left ovary vein. (d) Coronal reformatted image shows the filling defect (arrow) in the left ovary vein.

Image quality of 3D-CE-MRV was regarded as appropriate for evaluation of RVT, and good image quality was rated in 24 patients (75%, 24/32) and moderate in eight patients (25%, 8/32). 3D-CE-MRV detected thrombosis in 21 vascular segments (21.9%, 21/96) in 16 patients including five in right renal veins (Fig. 1), 13 in left renal veins (Fig. 2), and three in inferior vena cava (Fig. 3). 3D-CE-MRV also correctly detected left ovary vein thrombosis (Fig. 5) in one patient as CT venography. Negative findings were indicated in 16 patients on 3D-CE-MRV. Reader 1 detected all thrombosis except for one left RVT in chronic stage (Fig. 4). Reader 2 missed one right RVT but correctly indicated the left RVT. Reader 2 incorrectly rated another patient as having left RVT but correctly indicated the right RVT. Additionally, reader 2 also missed the left chronic RVTs in the same patient as reader 1. Thus, compared with CT venography, 3D-CE-MRV had a sensitivity and specificity of 94.1% and 95.5%, respectively, for detecting RVTs on a per-patient and a per-vessel basis for both readers. Table 1 shows the diagnostic performance of 3D-CE-MRV to detect RVT for readers 1 and 2, and both, which shows, with CT venography as reference standard, that the sensitivity and specificity of 3D-CE-MRA for RVT detection were 94.1%, 100%; 95.5%, 100% on a per-patient and a per-vessel basis; respectively. Excellent inter-reader agreement was found for the detection of RVT either on a per-patient basis or on a per-vessel basis (kappa value = 1.0 and 0.969, both P values <0.001).

Table 1.

Diagnostic accuracy of 3D-CE-MRV in the detection of renal vein thrombosis.

Analysis basis	Results				Statistical analysis (%)
Analysis basis	TP	TN	FP	FN	Sensitivity	Specificity	PPV	NPV	Accuracy
Patient basis
Reader 1	16	15	0	1	94.1 (71.3–99.9)	100 (78.2–100)	100 (79.4–100)	93.75 (69.8–99.8)	96.9 (83.8–99.9)
Reader 2	16	15	0	1	94.1 (71.3–99.9)	100 (78.2–100)	100 (79.4–100)	93.75 (69.8–99.8)	96.9 (83.8–99.9)
Both	16	15	0	1	94.1 (71.3–99.9)	100 (78.2–100)	100 (79.4–100)	93.75 (69.8–99.8)	96.9 (83.8–99.9)
Vessel basis
Reader 1	21	74	0	1	95.5 (77.2–99.9)	100 (95.1–100)	100 (83.9–100)	98.7 (92.8–99.9)	99.0 (94.4–99.9)
Reader 2	20	74	1	1	95.2 (76.2–99.9)	98.7 (92.8–99.9)	95.2 (76.2–99.9)	98.7 (92.8–99.9)	97.9 (92.7–99.7)
Both	21	74	0	1	95.5 (77.2–99.9)	100 (95.1–100)	100 (83.9–100)	98.7 (92.8–99.9)	99.0 (94.4–99.9)

3D-CE-MRV, 3D contrast-enhanced magnetic resonance venography; FN, false-negative results; FP, false-positive results; NPV, negative predictive value; PPV, positive predictive value; TN, true-negative results; TP, true-positive results.

Discussion

Our study demonstrated 3D-CE-MRV having a high accuracy for the detection of RVT in patients with nephrotic syndrome on a per-patient or on a per-vessel basis compared to multidetector CT venography.

RVT is a well-known complication of nephrotic syndrome (1), especially in patients with membranous nephropathy. In one recently published prospective study, Li et al. (4) showed a 33% incidence of RVT in patients with nephrotic syndrome and membranous nephropathy. Concomitant RVT in these patients with nephrotic syndrome can aggravate renal damage and result in refractory kidney disease, even life-threatening pulmonary embolism. Thus, it is necessary to screen RVT in these patients using appropriate imaging modalities. Selective renal venography is believed as the gold standard in the diagnosis of RVT; however, it is an invasive and costly procedure not suitable for screening an asymptomatic population at high risk for RVT (9). Selective renal venography also carries the potential risk of causing de novo RVT due to venous injury (1). Color Duplex sonography is of high sensitivity in experienced hands but it is highly operator-dependent (9). CT venography is currently the imaging of choice for diagnosing RVT with the sensitivity and speciﬁcity of almost 100% (1,2,16). The disadvantages of CT include exposure to radiation and use of nephrotoxic iodinated contrast media. MRI appears as an optimal choice for RVT detection and follow-up because gadolinium has an extremely good safety profile with no evidence of nephrotoxicity (17) and MRI does not employ ionizing radiation, hence the test can be repeated for follow-up purposes (9).

This study compared the diagnostic accuracy of 3D-CE-MRV and CT venography to detect RVT. If renal MRV proved valid, it would provide a viable alternative for patients having a contraindication to iodinated contrast material and would eliminate exposure of patients to ionizing radiation. Our renal 3D-CE-MRV protocols produced appropriate image quality to evaluate RVT presence in all patients included in this study. Importantly, compared with CT venography, our study demonstrated high sensitivities and specificities for detecting RVT either on a per-patient basis or on a per-vessel basis. Excellent inter-reader agreement was also observed. These findings indicated that renal 3D-CE-MRV is a viable alternative imaging modality to CT venography. We noted some previous non-enhanced MRI reports to detect RVT, but no conclusive results were indicated (11,12). Our proposed 3D-CE-MRV technique is a promising modality to detect RVT. Other advantages of MRI included simultaneous visualization of renal artery and renal parenchyma and function if multiple sequences are properly used. However, the following findings should be paid more attention: (i) chronic RVT, which can appear as poor visualization of renal vein and associated with collaterals around involved kidneys. We missed one case with chronic RVT due to this cause. Thus, poor visualization of renal vein highly indicates the presence of RVT in the patients with nephrotic syndrome. Although we missed one patient with RVT, simultaneous 3D-CE-MR pulmonary angiography detected the pulmonary embolism, thus this misdiagnosed RVT did not affect the patient’s treatment; (ii) Segmental clots or other venous clots detected occasionally within field of view should be carefully screened. We found a solitary ovary vein thrombosis in one patient in this study. Anticoagulation treatment was administrated when the diagnosis of ovary vein thrombosis was made.

We acknowledge our study has some limitations. First, we used multidetector CT venography rather than conventional venography as reference standard for RVT detection in this study because of the invasive nature of conventional venography and the wide availability and nearly 100% accuracy of CT venography (1,2,16). Second, our study included a small sample size, which can limit generalization of our results. A larger cohort study is needed. Third, there was a delay of 0–5 days between CT venography and 3D-CE-MRV. During that interval, all RVT patients had started receiving anticoagulation therapy; it is possible that a RVT may have diminished by the time of the MRV. However, we did not observe such findings.

In conclusion, our study demonstrated that 3D-CE-MRV had a high accuracy for the detection of RVT in patients with nephrotic syndrome compared to multidetector CT venography. It is of importance for patients suspected of having RVT but with contradictions to iodinated contrast medium and for children or young female patients, because renal 3D-CE-MRV can provide the same information as the currently available multidetector CT venography.

Footnotes

Funding

This work was partially supported by the grant for the Peak of Six Major Talents program of Jiangsu Province of China (No. WSW-122 for LJZ), the Medical Major Talents program of Jiangsu Province of China (RC2011129), and Program for New Century Excellent Talents in University (NCET-12-0260).

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