Kidney transplantation is the treatment of choicefor patients with end-stage renal disease, with upto a 91% to 95% 1-year graft survival rate.1
Renal transplant dysfunction can present with an in-creased serum creatinine level, decreased urine output,pain and tenderness over the graft, fever, and chills.However, quite often dysfunction is clinically asymp-tomatic, and presents with an isolated increase in se-rum creatinine level. A variety of imaging modalitiesare available to the clinician evaluating the kidneytransplant recipient, including ultrasonography (US),computed tomography (CT), magnetic resonance im-aging (MRI), nuclear medicine or molecular imaging(NM), and excretory urography. In addition, interven-tional radiologic techniques allow nonsurgical evalu-ation and potential simultaneous treatment options.This review focuses on the imaging characteristicsbased on disease-specific findings in kidney transplantrecipients. It is also very useful to recognize the time-line of complications after transplant surgery becauseit will aid the entire medical team immensely to con-clude the results of the imaging with a clinically rel-evant diagnosis (Fig. 1).
US with color Doppler (CDUS) is the first-line andmost widely used imaging modality because of its por-tability, rapid technique, lack of radiation or toxic dye,and its ability to provide physiologic information aboutthe allograft. The healthy allograft has the same appear-ance as a native kidney, although more detail usually isapparent because of its superficial positioning in the
Division of Nephrology, Department of Medicine, Indiana UniversitySchool of Medicine, Indianapolis, IN
Address reprint requests to Asif Sharfuddin, MD, Division of Nephrol-ogy, Department of Medicine, Indiana University School of Medi-cine, 950 W. Walnut St, R2-202, Indianapolis, IN 46202. E-mail:[email protected]
Seminars in Nephrology, Vol 31, No 3, May 2011, pp 259-271
liac fossa. The collecting system of well-functioningllograft often is slightly dilated in the immediate andarly postoperative period because of a high urineutput state, as well as because of the new surgicalreterovesical anastomosis. This is thought to be be-ause of surgically related swelling at the anastomosisnd because of a minor dysfunction of the ureteroves-cal valve junction. The vessels of the healthy trans-lant are also the same as the native kidney, althoughositioning of the graft in the iliac fossa may appear asortuous vessels on imaging, which may pose a diffi-ulty in assessing peak velocity measurements (asiscussed later) in evaluating for transplant renal ar-ery stenosis. The renal arterial vessels normally showlow-resistance waveform with a resistance index (RI)f less than 0.7. The normal peak velocity of theransplant renal artery has been reported in the rangef 180 to 210 cm/s, whereas the renal venous flow isat with low-velocity waveforms.2
NM imaging of the allograft is also a noninvasive,on-nephrotoxic tool to evaluate graft dysfunction,articularly in the early postoperative period. Cur-ently, the most frequently used radiopharmaceuticalgent is technetium-99m–mercaptotriglycine, and thetudy most commonly applied is dynamic nephroscin-igraphy (or NM renography). The first angiographichase assesses the flow and perfusion of the graft. Theecond parenchymal phase reflects the concentrationf the agent in the renal cortex, and the third and lastxcretory phase assesses the clearance of the agent,llowing assessment of the ureteral system. The activ-ty of the transplant as a relation of function of time isalculated based on a time-activity curve.
CT and MRI provide superb anatomic detail of theraft and surrounding tissues, although their use maye limited because of the requirement of dye agents,hich can be nephrotoxic (iodinated contrast medium)r carry the risk of nephrogenic systemic fibrosis (gad-
Acute tubular necrosis (ATN) and allograft rejection areone of the most common causes of impaired renal func-tion in the early postoperative period. Delayed graftfunction most often is caused by ATN and occurs in 10%to 30% of patients.3 Risk factors for ATN include de-ceased donor transplantation, prolonged warm or coldischemia time, hypotension, and bleeding. US findingsare nonspecific on gray-scale imaging and include graftswelling or enlargement, obscured corticomedullary dif-ferentiation, decreased echogenicity, and scattered heter-ogenous areas of increased echogenicity. CDUS imagingmay reveal increased RI (�0.80), although this finding isnot specific for ATN because it may be seen in calcineu-rin-inhibitor toxicity as well as in rejection. In ATN, NMimaging typically shows good perfusion on the angio-graphic phase, with preserved concentration during theparenchymal second phase. The excretory third phaseshows minimal excretion of the radiotracer agent into thecollecting system and bladder. Because of poor plasmaclearance of the agent, there is also high surroundingtissue background activity. In rejection, NM renographyshows decreased perfusion and delayed transplant visu-
Figure 1. Timeline of post-transplant complications based on thecomplications and when they are most often encountered help in ocertain complications can occur at any time after transplantation, whehematomas may occur after a biopsy even years after transplant). Rerefer to text for further details.
alization with poor parenchymal uptake and high back- t
round activity (Fig. 2). Because of the nonspecific andondiagnostic capability of these two modalities, clinicalorrelation is extremely important and US-guided renaliopsy remains the gold standard for confirmatory diag-osis.
US and NM imaging modalities, however, are usefuliagnostic studies to establish the presence of blood flowo the graft and the absence of a urine leak or obstruction.f there is absence of flow on either imaging modality,xtremely prompt re-exploration is absolutely required tottempt to salvage the graft from vascular catastrophesuch as arterial or venous thromboses. Hyperacute rejec-ions may present with acute vascular thrombosis and theraft is usually lost.
ATN is more likely to occur within the first few daysf transplantation, whereas in a nondesensitized recipi-nt, cellular rejection in the setting of modern immuno-uppression is more likely after 1 to 3 weeks of trans-lantation. Occasionally, nonspecific findings of mildydronephrosis and increased peak systolic velocitiesPSV) in the transplant renal artery may be seen inejection. Theoretically, this is thought to be caused bymmune-mediated inflammation of the ureter and trans-lant renal artery, respectively, leading to a functionalarrowing quite often seen more prominently at the anas-
st likely occurrence periods. Knowledge of these post-transplantg the most appropriate imaging evaluation. It should be noted thatothers are related to procedures such as biopsy (marked by X) (eg,
ons may occur at any time if immunosuppression is stopped. Please
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Imaging and kidney transplants 261
Calcineurin-Inhibitor Toxicity and BK Nephropathy
Calcineurin inhibitors (cyclosporine and tacrolimus) arepotent immunosuppression agents that have tremen-dously reduced the rates of acute rejection since theirintroduction. Drugs with supratherapeutic levels can benephrotoxic and present with graft dysfunction. US maybe completely normal or show nonspecific findings suchas graft swelling, increased or decreased renal echoge-
Figure 2. (A) Flow image and raw flow curve and (B) renogram imafunction secondary to ATN. The study shows a normal prompt perfuclearance to the transplanted kidney consistent with ATN. Tracemertiatide.
nicity, and loss of corticomedullary differentiation. a
DUS may show a nonspecific increase of greater than.80 in the RI. Consequently, diagnostic biopsy may beequired for diagnosis. Long-term chronic calcineurinnhibitor use can lead to chronic allograft nephropathy.S may show thinned cortices, smaller-sized kidneys, ore normal. The RI may be increased in chronic allograftephropathy and has been proposed to be a valuableredictor of long-term allograft survival when measured
d cortex curve NM images of a kidney transplant with delayed graftpattern to the transplant kidney. There is decreased excretion and
der activity is noted. Radiopharmaceutical used: 99m-technetium
ge ansionblad
t 3 months after transplantation.4 However, in another
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262 A. Sharfuddin
study, RI was associated with surrogate measures ofvascular compliance such as recipient age and pulsepressure index but not with chronic allograft damage,even when it was evaluated by histomorphometry, atleast in patients with stable renal function.5
BK nephropathy occurs in up to 5% to 10% of kidneytransplant recipients, usually within the first 12 to 18months of transplantation and presents as graft dysfunc-tion. Imaging findings are nonspecific, although fre-quently obstructive features are noted owing to the ure-teral involvement of the virus. Serologic testing andbiopsy usually is required for confirmatory diagnosis.6
Infrequently, focal parenchymal lesions are noted ongraft imaging. These may be donor-derived cysts, stones,or, rarely, even masses such as renal cell carcinoma orlymphomas. Post-transplant lymphoproliferative disor-ders are unique complications in transplant recipients,occurring in 2% to 10% of recipients, which may presentas a diffuse homogenous infiltrated lesion, focal intrapa-renchymal lesion, or be localized near the allograft. US,CT, and MRI all can be used in the diagnostic work-up ofpatients suspected of having post-transplant lymphopro-liferative disorder. Minimally enhanced masses of thetransplant renal hilum that encase the hilar vessels are acharacteristic finding in post-transplant lymphoprolifera-tive disorder on MRI. CT findings are nonspecific andmay include nonenhancing or peripherally enhancing,low attenuating masses (Fig. 3).7
COLLECTING SYSTEM
Urologic complications are much less frequent in thecurrent era of advanced surgical techniques as comparedwith earlier reports. Currently, rates vary from 3% to9%.8–11 The transplant ureter tends to be commonly in-volved because of its delicate limited vascular supply thatoriginates from the renal hilum. Hence, damage to smallaccessory arteries may lead to ischemia of the ureter. Thetechniques of ureteral anastomosis to the bladder used
Figure 3. (A) Transverse plane and (B) coronal plane CT imageskidney, which is heterogeneous in attenuation and measures 6.0 �remainder of the transplanted kidney is uniformly enhancing with inpost-transplant lymphoproliferative disease.
nowadays has a low incidence of urine leaks or obstruc- T
ion, and with many transplant centers using indwellingtents for 4 to 6 weeks, these complications are even lessommon. The upper part of prophylactic ureteral stentsually can be visualized as echogenic parallel lines inhe pelvis, whereas the lower end can be similarly seen inhe fundus of the bladder. The intramural portion of thetent occasionally can be detected, but because of thehape of the double-J stent, only short segments can beisualized at a time.
rinary Obstruction
reteral obstruction is reported to occur in about 2% to% of kidney transplant recipients. The site of obstruc-ion most commonly involved is the anastomosis into theladder, and roughly 90% of stenoses occur in the distalhird of the ureter. The most common causes for narrow-ng at the ureterovesical junction are scarring caused byschemia or rejection, technical errors during ureteralmplantation, and kinking. Other caused include extrinsicompression, perigraft fibrosis, intrinsic obstruction fromdema, clots, papillary necrosis, or nephrolithiasis. It isot uncommon to see a mild degree of hydronephrosis inhe early postoperative period because of edema at thereteroneocystostomy site and because the transplantedenal collecting system is denervated. Quite often, this iself-limited and usually resolves within a few days post-ransplantation. In the late transplant period, obstructionccurs as a result of adhesions, multiple procedures,ascular insufficiency, or fibrosis.12,13
The degree of obstruction can be expressed using arading system such as grade 1 through IV, or as mild,oderate, or severe, although these grades are subjective
nd operator and time-dependent (Fig. 4). Because theransplanted kidney is denervated, many patients will notomplain of the typical renal colic pain when obstructionccurs. Also, it occasionally becomes difficult to conclu-ively diagnose hydronephrosis, which is of clinical sig-ificance, causing deterioration of allograft function.
ing a soft-tissue mass centered at the midpole of the transplanted� 7.0 cm, extending from the lateral cortex to the renal hilum. Thenous contrast. A biopsy examination was performed and confirmed
show5.4
trave
his happens when there has been a prior obstruction in
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Imaging and kidney transplants 263
the past or if there are no serial prior images available.Once the urothelium has been stretched, the collectingsystem may never collapse again, making it very difficultto distinguish residual dilatation from functional obstruc-tion. Also, conversely, in the setting of severe rejectionsor ATN, the intrinsic tension may limit dilatation of thecollecting system, leading to underdiagnosis. ColorDoppler evaluation may provide limited information be-cause the RI may be increased in hydronephrosis, al-though an increased RI must be interpreted cautiously inthe context of the clinical setting because many scenarioswill increase the intrarenal RI. Overall, serial US pro-vides more sensitivity in many cases. Any bladder dis-order causing urinary retention can commonly causetransplant hydronephrosis. Hence, in all cases, when thepatient’s bladder is full, the bladder should be emptiedand the kidney transplant imaged again.
NM imaging in cases of urinary obstruction will revealnormal perfusion and parenchymal uptake of the tracer,but persistent radiotracer activity in the pelvis and col-lecting system. However, it is possible that NM imagingmay be less sensitive because there usually can be im-paired allograft function causing impaired uptake. Di-uretic response in NM imaging may help delineate ob-struction from residual dilation because an obstructedcollecting system will not respond to intravenous diuret-ics such as furosemide. A T1/2 (time it takes to reducestrength by one half) emptying time of longer than 20minutes indicates an obstructed collecting system be-cause a normal T1/2 emptying time is less than 15minutes. CT and MRI also are useful in excluding pos-sible extrinsic compression from perigraft fluid collectionor calculi.
Urine Leaks
Urine leaks can occur in 1% to 5% of renal transplantrecipients.12,14,15 They usually occur in the early post-transplant period within 1 to 3 weeks. Extravasationoccurs most commonly from distal ureteric sites eitherowing to rejection, ischemia, or at the ureteroneocystos-
Figure 4. (A) Gray-scale US shows moderate obstruct
tomy site owing to obstruction or incomplete bladder
losure. Caliceal and upper proximal ureteric leaks areess common and occur secondary to segmental infarc-ion in patients with accessory renal arteries or because ofigation of polar artery or as post-biopsy complication.
Patients with urine leaks present with pain, swelling,ischarge, and scrotal or labial swelling. US revealsonspecific, usually nonseptated, and well-defined, an-choic fluid collection usually adjacent to the lower polef the transplant. The leak may be extraperitoneal orntraperitoneal, in which case it may lead to ascites. If notreated immediately, it can become infected to form anbscess. Drainage can be performed under US guidancend testing the fluid for creatinine helps differentiate itrom seromas or lymphoceles. Fluid from urinomas willave a higher concentration of creatinine compared withhe serum. CT appearance of a urinoma is a peritransplantuid collection that may contain contrast-opacified fluid
hat is isodense to the collecting system fluid if the leaks active at the time of CT imaging. MRI reveals a fluidollection that has the same signal intensity as that inhe bladder. NM imaging shows extravasation of ra-iotracer into an area that is outside the collectingystem or an area that initially was cold. Very smalleaks may be picked up by delayed NM images be-ause accumulation of the tracer can be slow. Ante-rade pyelography or cystography usually is requiredo determine the exact location of the leak and plan forppropriate intervention.
PERINEPHRIC COMPLICATIONS
Perigraft fluid collections are quite common after trans-plantation, occurring in up to 10% to 50% of recipi-ents.16,17 The size, location, and change in character ofthese perigraft fluid collections are extremely importantfactors in determining their clinical significance.
Hematoma
In the immediate postoperative period, hematomas arethe most commonly encountered fluid collections. The
ydronephrosis. (B) Severe obstructive hydronephrosis.
overall incidence of postoperative hematomas varies
fbac
264 A. Sharfuddin
from 4% to 8%.18-20 They can be subcapsular or peri-nephric, and are usually small, with spontaneous resolu-tion. They also may occur as a consequence of trauma orbiopsy. US findings show an echogenic fluid collection inthe acute phase and become less echogenic over time asclot lysis occurs (Fig. 5). CT appearance also is timedependent. Acute hematomas have high-attenuationfeatures, whereas older hematomas containing lique-fied and serous components have lesser attenuations.These resolve to normal tissue attenuation over time ifthere is no further bleed. Similarly, MRI of hematomasare variable depending on the duration of the hema-toma. Large hematomas can displace the kidney andproduce hydronephrosis. Diagnostic testing can beperformed either using US or CT to aspirate the fluidcollection and rule out an abscess. Postbiopsy hema-tomas usually resolve, however, in appropriate clinicalsettings, serial imaging may be required to follow upthe extent of the bleed and to determine whether an-giographic intervention is needed.21
Lymphocele
Development of lymphoceles after kidney transplantationis a frequent complication with an incidence ranging
Figure 5. (A) Acute hematoma as imaged on gray-scale US. (B) Subacute subcapsular hematoma (arrowhead).
Figure 6. (A) Large peritransplant lymphocele seen as a relatively anecCDUS of same transplant showing increased intrarenal RI of 1.0 owing t
rom 0.6% to 33.9%. Lymphatic leakage can be causedy either disrupting lymphatic channels during the prep-ration of the recipient iliac vessels or alternatively isaused by the graft itself.22 A high percentage of
lymphoceles are diagnosed accidentally by postopera-tive ultrasonography, because the majority of perirenallymphatic collections are small and asymptomatic. Incontrast, larger lymphoceles often present with symp-toms, such as graft dysfunction caused by ureteral com-pression and bladder displacement, wound infection,deep vein thrombosis, abdominal pain, or leg edema, andrequire percutaneous or surgical drainage (Fig. 6). Sev-eral investigators reported an increase of lymphoceleincidence after the introduction of new immunosuppres-sive agents such as sirolimus. In addition, other studiesobserved an association of acute rejection episodes, in-creased body mass index, and high-dose steroid therapywith lymphocele development. Lymphoceles usually oc-cur medial to the transplant, between the graft and thebladder. They usually occur several weeks after trans-plantation.
On US imaging, lymphoceles are anechoic and mayhave septations. If they become infected they candevelop a more complex appearance. CT imaging
hematoma with septated complex fluid collection (arrow), along with
acute
hoic fluid collection causing extrinsic compression of the graft. (B)o extrinsic compression from the lymphocele.
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Imaging and kidney transplants 265
shows these lymphoceles to have variable characteris-tics and usually they are sharply circumscribed. TheirCT attenuation values are usually lower than those ofrecent hematomas and abscesses. Radionuclide andMRI studies are helpful for excluding the presence ofurine and blood, respectively. On T1-weighted images,lymphoceles tend to be of low signal intensity, and ofhigh signal intensity on T2-weighted images. Ultra-sound-guided percutaneous drainage with a successrate greater than 50% is recommended as the first lineof treatment.
Abscess
Infections are common after renal transplantation withmore than 75% of recipients suffering at least one case ofinfection during the first year after transplantation. Peri-transplant abscesses are an uncommon complication andusually develop within the first few weeks after trans-plantation and usually are caused by bacterial seeding ofa pre-existing fluid collection such as a lymphocele,hematoma, or urinoma. In a febrile transplant recipient,any peritransplant fluid collection must be presumed tobe infected.
Abscesses have a complex, cystic, nonspecific appear-ance on US imaging. US may show fluid collectioncontaining debris, low level echoes, and occasional gas.On CT, they manifest as heterogenous fluid-attenuatinglesions that may contain gas, which serves to differentiatethem from other collections.23 In emphysematous pyelo-nephritis, gas in the parenchyma of the renal graft pro-duces an echogenic line with distal reverberation arti-facts. This finding can be confirmed with abdominalradiography or CT. Any echogenicity within a dilatedcollecting system is usually clinically significant. Highlyechogenic, weakly shadowing masses within a trans-planted collecting system are fairly specific for fungusballs whereas the presence of low-level echoes in adilated pyelocaliceal system in a febrile patient suggestspyonephrosis. Retrograde pyelography also may showdistortion of the calices, a feature seen in tuberculosis ofthe renal transplant.21 However, one must remember thatthe absence of an imaging feature suggestive of an ab-scess does not exclude the presence of an infection.Hence, in the acute setting, US or CT-guided diagnosticand therapeutic aspiration of these fluid collections arethe preferred modalities.
Gadolinium-enhanced MRI will show an irregular en-hancing rim around a perinephric abscess.24 Gallium-67citrate and indium-111–tagged leukocyte NM imagingstudies are helpful for diagnosing renal or perirenal ab-scesses. Although, again, one must keep in mind otheretiologies such as rejection that also may enhance onsuch studies. Thus, extreme caution needs to be taken in
interpreting these studies.
c
VASCULAR COMPLICATIONS
Vascular complications consist of transplant renal arterystenosis, thrombosis and infarction, dissection, and post-biopsy complications.
Transplant Renal Artery Stenosis
Transplant renal artery stenosis (TRAS) is a well-recog-nized complication that usually is diagnosed within thefirst year after transplantation. It has an incidence rate of8.3 cases per 1,000 patient-years.25 About 50% of renalrtery stenoses occur at the site of the anastomosis. It alsoas been shown that end-to-end anastomoses have ahree-fold greater risk of stenosis than end-to-side anas-omoses.26
Pre-anastomosis stenosis usually occurs as a result ofxisting recipient atherosclerotic disease or in the donoressel. Anastomotic stenosis usually is the result of ves-el perfusion injury, incorrect suture technique, or in-ammatory fibrotic reaction to the suture material. Posta-astomosis stenosis can occur secondary to rejections,nd in some cases has been reported to be secondary toiral infections. TRAS is more common after transplantsrom deceased donors as compared with live donor trans-lants in most of the studies, suggesting the possibilityhat immunologic factors and prolonged cold ischemialay a role.
TRAS can present with severe hypertension refractoryo medical therapy, hypertension, and the presence of anudible bruit over the graft, or hypertension associatedith unexplained graft dysfunction. CDUS is a well-
ccepted screening tool for the assessment of renal vas-ulature in cases suspected of having TRAS. Evenhough CDUS is observer dependent, it is easy to use,oninvasive, inexpensive, and a highly reliable tool inighly experienced trained centers. CDUS shows stenoticegments as focal areas of color aliasing as a result ofncreased flow velocity. These areas can be evaluatedelectively with duplex Doppler techniques to character-ze and grade the flow disturbance. Many criteria are usedo detect TRAS using CDUS. PSV, intrarenal dampeningf flow, and RI are the important diagnostic parameters.oppler criteria for significant stenoses include the fol-
owing: (1) focal frequency shifts greater than 7.5 KHzwhen a 3-MHz transducer is used) or PSV greater than
m/s, (2) a velocity gradient between stenotic andrestenotic segments of more than 2:1, and (3) markedistal disturbance (spectral broadening) (Fig. 7). In theenal parenchyma, tardus-parvus waveform abnormal-ties can be observed.21 Although various thresholdsave been reported for PSV, its sensitivity and speci-city still is not absolute. The machine’s software isependent on the operator’s estimate of the angle ofnsonation. The accuracy of the angle correction inurn is dependent on the course of the artery. Trans-lant renal arteries with straight, well-delineated
ourses usually give a more confident diagnosis with
vdormnei
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ctuaHrpma
266 A. Sharfuddin
higher sensitivity and specificity. Documentation ofhigh PSV alone in CDUS with the absence of clinicalfindings usually indicates that the patient requires acloser follow-up evaluation.
MR angiography (MRA) can be used to diagnose renalartery stenosis in renal transplants (Fig. 8). MRA has theadvantage of requiring either no contrast material or agadolinium chelate that is not nephrotoxic. However, intransplant recipients with a glomerular filtration rate ofless than 30 mL/min, gadolinium-based contrast agentscannot be used because of its risk of causing nephrogenicsystemic fibrosis. Some reports have found that MRAcorrelated with the gold standard of digital subtractionangiography whereas others have reported that as com-pared with CDUS and digital subtraction angiography,MRA is of limited diagnostic value for making a diag-nosis of TRAS because of a 75% incidence of false-positive reports with MRA. The reason attributed to this
Figure 7. (A) Normal CDUS showing normal PSV at the anastomoswith TRAS, with a PSV of 4.73 m/s at the anastomosis. Note color dDoppler wave form (lower section).
Figure 8. MRA showing transplant renal artery stenosis in a patient
who had undergone transplantation 8 months earlier who presentedwith severe uncontrolled hypertension.
ery high false-positive rate is a major intravoxel phaseispersion, which may occur because of either tortuosityf the vessel or because of sharp angulations between theenal artery and the parent vessel. One also should re-ember that the incidence of mild and moderate vessel
arrowing at the arterial anastomosis is very high in thearly period after kidney transplantation and most likelys owing to surgery-related tissue edema.
Renal scintigraphy and time-activity curves show re-uced perfusion in transplants with complete vascularbstruction and renal artery stenosis. This finding isonspecific, however, because it may be seen with otherauses of parenchymal failure, including graft rejectionnd urinary obstruction. Hence, it has no role in theiagnostic evaluation of suspected TRAS.
The gold standard for the diagnosis of TRAS remainsonventional iodine-contrast, enhanced digital subtrac-ion angiography. Carbon dioxide angiography may besed as a non-nephrotoxic procedure, but image qualitynd the sensitivity of diagnosis is quite often less reliable.emodynamically significant TRAS is indicated by nar-
owing of the luminal diameter by more than 50%, or byressure gradient measurements across the stenosis ofore than 10% greater than peak systolic blood pressure
cross the stenosis27 (Fig. 9). Surgical correction of graftTRAS usually is successful, but it is associated withsubstantially high morbidity and usually is reserved forthose cases in which angioplasty or stent placement isnot technically possible or successful. Hence, primarytreatment of TRAS by percutaneous transluminal an-gioplasty with or without stent placement results ingood intermediate-term patency and is associated withsignificant early improvement in blood pressure andgraft function.28 Because of its low level of morbidity,relatively modest cost, and effectiveness, percutaneoustransluminal angioplasty is accepted as the initial treat-ment of choice. Clinical success rates resulting insubstantial initial improvement or cure have been re-ported in 73% to 90% of patients. However, up to 5%
th a value of 0.96 m/s and normal RI of 0.69. (B) CDUS in a patienttion suggesting turbulent flow along with spectral broadening of the
is wiistor
to 20% of stenoses may have a recurrence of the
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Imaging and kidney transplants 267
stenosis and require repeat dilation or stenting formaximum success.26,29,30 A suggested algorithm towork-up recipients with suspected transplant renal ar-tery stenosis is shown in Figure 10.
Renal Artery Thrombosis and Allograft Infarction
Nowadays, renal artery thrombosis is a rare complicationwith a prevalence of 0.5% to 2% and usually occurs inthe early post-transplant period. However, it is a majorcause of early (�1 wk) graft loss.31 Infarction as a resultof renal artery thrombosis may result from faulty suturetechnique, hyperacute rejection, a thrombogenic state,anastomotic occlusion, arterial kinking, or intimal flapwith dissection. It is also possible to see segmental in-farcts that may be focal or diffuse and may occur as part
Figure 9. (A) Percutaneous transluminal angiography showing narroin diameter. (B) Angiogram after angioplasty and stenting showing r
Figure 10. Proposed algorithm for the diagnostic work-up and treatmentangioplasty.
f an embolism, rejection, or as a result of an unassoci-ted vascular thrombosis or vasculitis32 (Fig. 11).
Clinically, patients with renal transplant infarctionresent with anuria and often with swelling and tender-ess over the graft. Despite the fact that the graft lacksnnervation, the inflammation within the transplantedidney incites an intense inflammatory response in thedjacent visceral peritoneum leading to severe localizedain over the graft.
In renal artery thrombosis, flow in both main andntrarenal arteries is completely absent at CDUS. Seg-ental infarcts appear as poorly marginated, hypoechoicasses, or a hypoechoic mass with a well-defined echo-
enic wall. Global infarction will appear as a hypoechoiciffusely enlarged kidney.21 At color or power Doppler
of the proximal renal artery (arrow) with more than a 75% reductionation of flow with normal renal artery lumen diameter.
wing
of recipients with suspected TRAS. PTA, percutaneous transluminal
mtgactcu
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268 A. Sharfuddin
imaging, segmental infarcts appear as wedge-shaped ar-eas without color flow in, although these findings alsomay be seen in severe pyelonephritis or transplant rup-ture.
Contrast CT can be used to detect perfusion deficits inthe renal graft parenchyma, but it is generally not used inpatients with allograft dysfunction because of the risk ofradiocontrast-induced nephrotoxicity further compro-mising renal function. To confirm equivocal results asto the nature of the US findings, angiography or MRAmay be performed. Phased-array surface coils provideexcellent signal-to-noise information that permitsrapid acquisition of high-quality images without theuse of potentially nephrotoxic agents. Dynamic en-hanced MRI can be useful for diagnosing both seg-mental and global infarctions as well as renal arterythrombosis. Infarctions show loss of corticomedullarydifferentiation on T1- and T2-weighted images withhomogenous low-intensity signal on T1- and high sig-nal intensity on T2-weighted images. In addition, MRIhas been helpful for showing small infarcts caused byiatrogenic drug-induced vasculitis.33
NM images can show lack of perfusion, absent visu-alization of the transplanted kidney, with poor clearanceof the tracer, along with a photopenic space in the ex-pected location of the transplant bed. In technetium-99mdynamic radionuclide studies, a photopenic region orwedge-shaped cold defect may be seen. However, thesefindings are not specific because hyperacute or acceler-ated acute rejection, cortical necrosis, and renal veinthrombosis can have similar clinical, Doppler US, andscintigraphic features.
Figure 11. Angiogram showing loss of perfusion in the cortex (ar-rows) owing to infarct in a renal transplant secondary to dissection.
ay be valuable in treating infarctions and renal arteryhrombosis, although once graft thrombosis has occurred,raft loss usually is inevitable. Hence, early diagnosisnd treatment are vital for allograft salvage. There arease reports of successful catheter-directed thrombolyticherapies used to salvage the graft, but depending on theause and duration of the occlusion its roles remainsnclear.34 Catheter-directed therapies within the first 2
weeks of transplantation are not recommended becauseof the risk of disruption of the immature vascular anas-tomosis.
Arteriovenous Fistulas and Pseudoaneurysms
Despite advances in noninvasive diagnostic tests andtechniques, percutaneous core needle biopsy is still con-sidered the gold standard for evaluating allograft dys-function and commonly is performed in transplant recip-ients. US-guided transplant biopsy is relatively easy toperform but does carry a risk of known vascular compli-cations such as arteriovenous fistulas (AVFs) and pseu-doaneurysms. The reported rate of postbiopsy complica-tions including macroscopic hematuria ranges from 1%to 7% of biopsies and usually is self-limiting.35-39
Gray-scale US imaging cannot identify these smallascular complications, which usually present with per-istent hematuria or hypertension. CDUS can easily showVFs and pseudoaneurysms as localized areas of disor-anized color that extend outside the confines of theormal vessel in the renal parenchyma. This appearances caused by perifistula vibration and is detected with theore sensitive color Doppler units. The vibrating inter-
aces in the perivascular tissue produce phase shifts in theeflected sound wave and result in random color assign-ent in this region. AVFs classically appear as abnormal
igh-velocity turbulent flow isolated to a single segmen-al or interlobar artery and paired vein that producesliasing on color Doppler images. The feeding arteryhows a high-velocity, low-resistance waveform, and theraining vein shows arterialization.21,40 A mimic of an
AVF is an intrarenal arterial stenosis that causes similarhigh-velocity flow and tissue vibration, except there is nochange in venous waveform.
Pseudoaneurysms after a biopsy are usually intrarenal,although extrarenal pseudoaneurysms can be seen be-cause of incorrect surgical anastomosis or peri-anasto-motic infections. On gray-scale US images, pseudoaneu-rysms appear as simple or complex renal cysts, but withcolor imaging, highly vascular intracystic or swirlingflow is seen (Fig. 12). Pseudoaneurysms with a narrowneck and no venous communication show a classic ma-chine-like alternating to-and-fro Doppler spectrum attheir necks. Pseudoaneurysms can be associated withAVFs and these show a high-velocity, low-resistancespectrum at their necks, with minimally pulsatile high-velocity flow in the draining vein.34,40 MRA can be auseful confirmatory imaging tool if CDUS is inconclu-
sive, although its role may be limited because of spatial
ats
cifcisgaiapttrej
afasts
ent fl
Imaging and kidney transplants 269
resolution issues. Conventional angiography is the imag-ing technique of choice for defining the extent of theAVF or pseudoaneurysm and simultaneous treatmentplanning.
Such complications after biopsy generally are treatedconservatively because most pseudoaneurysms resolvespontaneously. Up to 70% of all AVFs resolve sponta-neously within 1 to 2 years, whereas the remaining can besymptomatic or persist.41 Large (�2 cm diameter) orprogressively enlarging pseudoaneurysms require inter-vention. Super-selective transvascular catheterization isused to determine the size and location of the AVF orpseudoaneurysm, which in turn determines which em-bolic agent to use. Large AVFs are treated more easilywith steel coils as compared with an absorbable gelatinsponge (Gelfoam; Baxter Healthcare Corporation, Hay-ward, Cal), which may pass through the fistulous com-munication and embolize the systemic circulation. Pe-ripheral lesions may be difficult to catheterize selectively,but a flow-directed detachable balloon can be deliveredto the proximal site.42 Because of the end-arterial supplyof the renal vasculature, a proximal occlusion is adequateto treat the AVF or pseudoaneurysm.41,43
Renal Vein Thrombosis
Renal vein thrombosis is an unusual and rare complica-tion of transplantation occurring in less than 5% of pa-tients and usually in the first postoperative week. Itpresents with acute anuria, swelling, and tenderness overthe graft. Extreme hypovolemia, hypercoaguable states,venous compression from a peritransplant fluid collec-tion, dysfunctional venous anastomosis, and slow flowsecondary to rejection may lead to renal vein thrombo-sis.44,45
Gray-scale US findings in renal vein thrombosis in-clude an enlarged kidney, whereas CDUS shows thatvenous flow is reduced or absent, and there is increasedresistance on the arterial side, often resulting in reverseddiastolic flow on Doppler images. MR venography can
Figure 12. (A) Gray-scale US imaging showing a hypoechoic cyst-a highly vascular lesion in the corresponding cyst region with turbul
help confirm this complication in transplants. Similar to a
rterial thromboses, early recognition of renal veinhrombosis is crucial because the allograft could rarely bealvaged by prompt venous thrombectomy.
NEWER TECHNIQUES IN IMAGING KIDNEYTRANSPLANTS
Recent technical developments in all imaging modalitiespromise to improve and enhance the sensitivity and spec-ificity for more accurate clinically relevant diagnosis.One such example is microbubble contrast enhancement.Contrast-enhanced sonography (CES) has a much highersensitivity and specificity and might be considered themodality of choice for the detection of infarction andcortical necrosis, particularly in ischemic renal trans-plants.46 CES provides quantitative information on mi-rovascular perfusion of the renal allografts and offersmproved diagnostic significance compared with CDUSor the detection of chronic allograft nephropathy. Inontrast to conventional CDUS resistance and pulsatilityndices, renal blood flow estimated by CES was highlyignificantly related to serum creatinine in kidney allo-rafts. Perirenal hematoma, ATN, and vascular rejectionre associated with characteristic changes of the time-ntensity curve of CES. Quantitative determination ofrterial arrival of an US contrast medium in the earlyhase after kidney transplantation has been studied andhis may identify acute rejection earlier than conventionalechniques.47 Further research, which is ongoing, into theole of CES in other disease states will be needed tostablish its place in the diagnosis of acute kidney in-ury.48
Ultra-small particles of iron oxide are macromoleculargents based on iron, 20 to 30 nm dextran coated in aormulation chemically known as ferumoxtran-10, thatre not filterable across the glomerulus. Researchers havehown that, in renal transplant models of allograft rejec-ion, uptake of ultra-small particles of iron oxide corre-ponds with the loss of signal in the renal parenchyma
tructure after a renal transplant biopsy. (B) CDUS imaging showingow compatible with a pseudoaneurysm.
like s
nd the degree of lymphocytic infiltration. Furthermore,
270 A. Sharfuddin
others have proposed that graft flourodeoxyglucose pos-itron emission tomography (FDG-PET) imaging is a newoption to noninvasively, specifically, detect earlier, andfollow-up acute renal rejection, which could be differen-tiated from ATN and calcineurin toxicity using this tech-nique.49
There is hope that further advances in all imagingtechniques will continue to expand the field of imaging inkidney transplantation. Currently, US and the other mo-dalities remain an indispensible tool for evaluating thekidney transplant recipient with graft dysfunction orpost-transplant–related complications.
ACKNOWLEDGEMENTSFigures were kindly provided by Dr. Bilal Tahir, Department ofRadiology, Indiana University School of Medicine.
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