Imaging in renal transplant: Review

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Review Article

Imaging in renal transplant: Review Hira Lal a,*, Rajesh V. Helavar b, Shivanand Gamanagatti c, Suruchi Jain d, Rakesh Kumar e a

Asociate Professor, Department of Radiology, Sanjay Gandhi Post Graduate Institute of Medical Science, Rai Barielly Road, Lucknow, Uttar Pradesh 226014, India b Senior Resident, Department of Radiology, Sanjay Gandhi Post Graduate Institute of Medical Science, Rai Barielly Road, Lucknow, Uttar Pradesh 226014, India c Additional Professor, Department of Radiology, All India Institute of Medical Sciences, New Delhi, India d Senior Resident, Department of Nuclear Medicine, Sanjay Gandhi Post Graduate Institute of Medical Science, Rai Barielly Road, Lucknow, Uttar Pradesh 226014, India e Professor, Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India

article info

abstract

Article history:

Renal transplantation has transformed the management of end stage renal disease (ESRD),

Received 12 December 2013

along with prolonging survival it offers good quality of life with low morbidity. Imaging

Accepted 10 January 2014

plays an important role in the diagnosis of complications arising in renal transplant. Ul-

Available online 23 January 2014

trasound (US) with Doppler is the first-line imaging modality for evaluation of renal graft, with US, Doppler and nuclear medicine being the main imaging modalities. Computed

Keywords:

tomography scan (CT), Magnetic resonance imaging (MRI) and digital subtraction angiog-

Renal transplant imaging

raphy (DSA) are used as problem solving tools in indeterminate cases. Interventional

Ultrasound

radiology plays a crucial role in the management of complications. Use of real time ul-

Doppler

trasound guidance for percutaneous biopsy is now almost universal.

Magnetic resonance imaging

1.

Copyright ª 2014, Indian Society of Organ Transplantation. All rights reserved.

Introduction

Renal transplantation is the treatment of choice for end stage renal disease (ESRD) patients. With improved transplantation technology, new generations of immunosuppressive agents and developments in graft preservation techniques, shortterm of the grafts improved dramatically. However, the improvement in long-term graft survival remains a challenge. Complications arising in the renal allografts are not uncommon. Major causes of renal transplant dysfunction are acute tubular necrosis (ATN), rejection, toxicity from medication, renal artery stenosis, renal vein thrombosis, postrenal biopsy

arteriovenous fistula and pseudoaneurysms, urinary leaks and perinephric collections (abscess, lymphocele etc) and graft hydronephrosis. Radiologic imaging plays an important role in evaluation of the graft kidney. The following imaging modalities are used in diagnosis and management of posttransplant complications.

2.

Ultrasound

Typically renal transplants are located in false pelvis (in right iliac fossa) and are quite superficial, hence readily accessible

* Corresponding author. Tel.: þ91 (0) 522 2494583, þ91 800 490 4486. E-mail address: [email protected] (H. Lal). 2212-0017/$ e see front matter Copyright ª 2014, Indian Society of Organ Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.ijt.2014.01.005

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with US. Advantages of ultrasound include lack of ionizing radiation, portability, less expensive, and lack of potentially nephrotoxic iodinated contrast agents. The operator dependence of US is, however, a relative limitation. Ultrasound is a valuable toolintheimmediatepost-transplantperiodaswellasforlong-termfollow-up. Gray scale ultrasound appearance of healthy transplant kidney resembles those of a normal native kidney (Fig. 1). Gray scale images are obtained to evaluate for transplant hydronephrosis, peritransplant fluid collections, and renal cortical thickness (Fig. 1). Color Doppler images are obtained to evaluate the patency and direction of flow in transplant arteries and veins (Figs. 2 and 3). Spectral analysis of vascular waveforms and velocities can provide information about a range of pathologies such as renal artery stenosis (Fig. 4). US is used as a routine study to evaluate the transplant within the first 24 h after transplantation to detect or rule out vascular complications. In the perioperative period, US can detect renal artery thrombosis or renal vein thrombosis. It is commonly used for first-line evaluation in the setting of transplant dysfunction. Gray scale findings of transplant dysfunction on US include a decreased cortico-medullary differentiation, reduction in renal sinus echoes, increased and reduced renal parenchymal echoes, increased cortical reflectivity. However, these features occur well after the onset of the dysfunction and are arbitrary and inconsistent and hence of limited value. Doppler indices are suggested for evaluation of renal graft. Many studies in the past have suggested that resistive index (RI) measured by duplex Doppler US is not sensitive or specific in identifying the cause of functional transplant dysfunction.1,2 However, recent studies have shown that renal arterial RI is useful in predicting graft survival, especially when using a lower RI cut-off of 0.8.3,4 Allograft recipients with a resistive index of 0.8 or greater have higher mortality than those with a resistive index of less than 0.8 at 3, 12, and 24 months after transplantation.5 Abnormal resistive indices indicate allograft dysfunction but do not reliably demonstrate the cause. Pulsatility index of greater than 1.8 is considered abnormal. Doppler US is also a very reliable and noninvasive tool to monitor the effectiveness of revascularization in patients with renal artery stenosis (RAS).6 Tardus parvus waveform can be seen within the kidney downstream to the stenosis; however, due to the superficial location of the transplant kidney,

evaluation of the main renal artery is better. Peak systolic velocity (PSV) in the renal artery is commonly used as the parameter to assess for the presence of renal artery stenosis on Doppler (Fig. 5). Cut-off values of 200e300 cm/s have been proposed for the diagnosis of RAS in various studies.7,8 An acceleration time (AT) of 90 ms or less, is usually considered as normal. Another parameter that can be used is the renal to iliac artery ratio (RIR), which has been shown to have a sensitivity of 90% and specificity of 96.7% using a cut-off value of 1.8. As evaluation for renal artery stenosis with US Doppler is operator dependent, magnetic resonance angiography (MRA) or CT angiography (CTA) may be more reliable than with US Doppler. US appearance of renal artery thrombosis is striking, with complete absence of flow in the renal vessels on color flow and spectral analysis. It is important to remember, however, that absent flow within the kidney can also be seen in patients with hyperacute rejection and renal vein thrombosis.9 Reversal of flow in the renal artery in diastole has been seen in renal vein thrombosis10; however, this reversal has been shown in ATN, rejection, low cardiac output, and nephrosclerosis as well.11 US is a useful tool for detection of postbiopsy arteriovenous fistulas and pseudoaneurysms, which can affect allograft function if they are large.

Fig. 1 e Longitudinal gray scale ultrasound through normal transplant kidney.

Fig. 3 e Power Doppler image of transplant kidney showing normal flow.

Fig. 2 e Color Doppler image through mid pole of transplant kidney showing normal color flow.

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Fig. 4 e Doppler through transplant renal artery showing normal spectral waveform with RI of 0.61.

US can identify postoperative fluid collections like urinoma, lymphocele, hematoma and abscess, but it cannot differentiate between them (Fig. 6). In order to differentiate these entities, aspiration is required, and this is commonly performed with US guidance. Hydronephrosis can also be easily identified with US (Fig. 7); however, it should be interpreted in correlation with biochemical parameters since reflux can give a similar appearance as well. Urine leak may appear as a fluid collection on US, but radioisotope scan would be more helpful.9 Minimal splitting of the pelvicalyceal system can be seen in transplant kidneys and is not to be confused for hydronephrosis. US is also useful in guiding renal transplant biopsies since serum creatinine is insensitive for detecting early graft pathology and cannot be relied on for assessment of adequacy of immunosuppression. The complication rate from renal transplant biopsies is low, with a reported rate of 0.4%e1%.12 B-mode and Doppler ultrasonography have limitations in the assessment of the renal transplant microcirculation, cortical perfusion. Contrast-enhanced ultrasound (CEUS) has been used by some investigators to evaluate graft perfusion not only in large arteries but within the cortex as well.13

Fig. 6 e Gray scale ultrasound image showing a collection along the upper pole of the transplant kidney mildlyindenting the renal parenchyma.

Ultrasound contrast agents (UCA) are microbubbles of a complex gas stabilized by a phospholipid, or polymer shell, are small enough to cross capillary beds but are too large to enter the interstitial fluid and act as intravascular agents. Renal ultrasound contrast agent dynamics differ from CT and MR contrast agents; they remain entirely intravascular, are not excreted by the kidneys and therefore have no nephrographic or excretory phase. Following an intravenous bolus of UCAs the cortical phase begins 10e15 s after injection and lasts 2 e 40 s followed by a slower medullary phase lasting 45e120 s. CEUS allows imaging of vessels down to 100 mm in diameter which is well below the 1 mm resolution limit of conventional Doppler techniques. Ultrasound contrast agents (UCA) are simple to use and are well tolerated by patients. They can be safely used in renal impairment and obstruction unlike iodinated or gadolinium based contrast agents used in CT and MRI respectively.14

3.

Computed tomography (CT)

CT scan is typically not used to evaluate renal transplant dysfunction due to concerns of nephrotoxicity from iodinated

Fig. 5 e Doppler showing elevated velocity (PSV 238 cm/s) in the main renal artery suggestive of stenosis (Image courtesy Dr Prakash Naik, Consultant Radiologist, Columbia Asia Referral Hospital Bangalore, India).

Fig. 7 e Longitudinal gray scale image of transplant kidney showing hydronephrosis.

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Fig. 8 e a and b: Coronal reformatter CT angiograms of the transplant reanl atery showing heavily calcified walls of the external iliac artery and two renal arteries anastamosed with the external iliac artery.

contrast; however, in patients with suspected renal artery stenosis, CT angiography (CTA) can provide additional information before a percutaneous catheter angiography is performed. CTA allows for anatomic depiction in great detail and has a high diagnostic accuracy for detecting vascular complications (Fig. 8a, b). CTA, however, has the drawback of contrastinduced nephrotoxicity and radiation exposure in addition to insensitivity to mild renal artery stenosis.15 Hence iodinated contrast agents should be used with caution in patients with renal dysfunction due to potential nephrotoxicity. In addition to vascular complications, rarely a non-contrast CT could also be used to assess for hydronephrosis, failed grafts which are difficult to assess on US (Fig. 9) and change in the size of fluid collections especially in the presence of air (Fig. 10).

4.

Magnetic resonance imaging (MRI)

MRI is being increasingly used for renal arterial visualization in renal transplants to assess for renal artery stenosis

Fig. 9 e Coronal reformatted CT scan with oral contrast through lower abdomen showing renal graft in the right iliac fossa with calcifications.

(Fig. 11).16 In addition there are concerns about toxicity from gadolinium in this patient population causing NSF.17 However, due to the noninvasive nature of the examination, Magnetic resonance angiography (MRA) has been used for evaluating renal artery stenosis in post-transplantation patients. MRA, however, suffers from a few pitfalls that may lead to false diagnosis of stenosis or overestimation of a stenosis. These include artifacts caused by metallic surgical clips near the transplant artery that result in signal drop overlying the vessel, giving the false impression of stenosis, and bright signal at the margin of the signal drop in the soft tissue next to the renal allograft due to metallic clips, and venous overlaps due to inaccurate timing of the arterial bolus. Careful evaluation of the source images and multiplanar reformats will help solve these problems.18 In addition to depicting areas of stenosis in the main renal artery, MRA is also able to depict areas of infarction within the kidney, which may be seen as areas of heterogeneous T1 and T2 signal intensity and as focal areas of non-enhancement on the postcontrast images. Newer techniques like non-enhanced MRA with steady-state free precession imaging and ferumoxytol

Fig. 10 e Axial non-contrast CT of the lower abdomen showing transplant kidney in the right iliac fossa with an air filled collection in the parenchyma.

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Fig. 11 e Oblique reformatted contrast-enhanced MR angiogram showing transplant renal artery stenosis (arrow).

enhanced MRA can help avoid gadolinium in these patients and avoid the risk of NSF.19 Changes in the cortico-medullary differentiation on MRI have been described in postrenal transplant patients with cyclosporine toxicity, rejection, and ATN.2,20,21 Newer functional MR imaging techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), tractography, blood oxygen level dependent (BOLD) and arterial spin labeling are being increasingly used for evaluation of transplant kidneys. These modalities offer promise as they do not use gadolinium. Diffusion weighted imaging shows promise in differentiating normal grafts from those with graft dysfunction. The apparent diffusion coefficient (ADC) values of renal allografts with acute functional impairment are lower compared with normal grafts (Fig. 12a, b). Grafts with ATN have low ADC values and a characteristic heterogeneous mosaic appearance. DWI has a high sensitivity and specificity in diagnosis of acute renal allograft dysfunction. The clinical experience with

DWI is limited and further studies with larger cohorts is necessary.22 Diffusion tensor imaging (DTI) is a promising noninvasive technique for functional assessment of renal allografts. Fractional anisotropy values in the renal medulla exhibit a good correlation with renal function.23 Changes in allograft function and microstructure can be detected and quantified using DTI. However, to prove the value of DTI for standard clinical application especially correlation of imaging findings and biopsy results is necessary.24 BOLD imaging depends on contrast generated by changing levels of paramagnetic deoxyhemoglobin with a decrease in intrarenal T2* during hypoxia taken as a reflection of increasing concentrations of deoxyhemoglobin (Fig. 13a, b). BOLD imaging can non-invasively detect change in intrarenal oxygenation and renal hypoxia induced by RAS.25BOLD MRI appears to be valuable to discriminate between acute rejection and acute tubular necrosis in early renal allograft dysfunction. The R2* levels in grafts with acute rejection were significantly decreased and increased in an early stage of acute tubular necrosis.26 Parallel imaging has the major virtue of reducing acquisition times while preserving spatial resolution. BOLD and diffusion weighted imaging are increasingly used in the assessment of acute renal allograft dysfunction.25,27 Flow sensitive alternating inversion recovery arterial spin labeling (FAIR ASL) can be used to evaluate perfusion in transplant kidneys.

5.

Nuclear medicine

Radionuclide tests are valuable in renal transplantation since they provide a noninvasive means to evaluate transplant function qualitatively and also screen for surgical complications. Only scintigraphic studies are able to separate function of the graft from residual function of the native kidneys.28 There are a wide variety of techniques advocated in renal transplants.28 The most commonly used procedure is renal

Fig. 12 e a and b: Diffusion weighted image with corresponding ADC map of the transplant kidney.

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Fig. 13 e a and b: R2* images with corresponding R2* map of renal allograft.

scintigraphy with combined imaging. Renal scintigraphy can assess complications like acute rejection, vasomotor nephropathy, vascular problems and leaks. Although findings of renal scintigraphy are often non-specific, specificity improves when findings are correlated with time elapsed since transplantation. It is recommended that a base line scan should be obtained within a day or two of transplant so as to detect subtle abnormalities in the follow up period. Apart from the visual interpretations of the scans many semi-quantitative and quantitative indices of renal function like ERPF, GFR and Tc 99 MAG3 clearance can be obtained from renal scintigraphy. Newer modalities like PET CT and PET MR are not of great help in evaluation of renal allograft in the present scenario.

6.

Angiography

With the availability of MRA, percutaneous catheter angiography is rarely performed for the diagnosis of renal artery stenosis. However, percutaneous transluminal angioplasty (PTA) and stenting (PTAS) (Fig. 14a, b) is the treatment of choice for renal artery stenosis, with a reported success rate of 65%e100%.29e33 The complication rate of PTA and PTAS is low at approximately 0%e10% compared to surgery, which has a graft loss rate of 15% and mortality rate of 5%. Superselective embolization is also effective in treating post-biopsy pseudoaneurysms and arteriovenous fistulae in renal transplants with minimal loss of renal parenchyma.34

Fig. 14 e a and b: Digital subtraction angiograms showing anastamotic site stenosis in the transplant renal artery before (a) and after (b) balloon dilatation.

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Conclusion

 Renal transplant dysfunction is a devastating event and appropriate management of immunosuppression and complications that arise in these patients is necessary to avoid graft failure.  US with Doppler is the primary imaging modality for evaluating renal transplant.  Radionuclide tests using Tc-99m MAG3 or Tc-99m DTPA can evaluate renal transplant function qualitatively and screen for surgical complications.  MRI and CT can also be used for evaluating renal transplants; however, concerns about iodinated contrast media and gadolinium toxicity in a population at risk of renal dysfunction needs to be considered.

Conflicts of interest All authors have none to declare.

references

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