Renal Artery Scintigraphy

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CHAPTER 108 Renal Artery Scintigraphy

Lina Mehta, James K. O’Donnell, Peter Faulhaber

Renovascular hypertension (RVH) secondary to renal artery stenosis (RAS) can be a challenging diagnosis to make. The presence of RAS does not necessarily imply RVH. There are many radiologic methods of investigating RAS, including Doppler ultrasound, computed tomography, magnetic resonance imaging, nuclear renography, and angiography. Most imaging modalities assess renal artery stenosis, but the functional information provided by nuclear renography augmented with an angiotensin-converting enzyme inhibitor (ACEI) allows for the detection of renovascular hypertension.

In patients with a hemodynamically significant reduction in renal artery caliber, there is a reduction in renal perfusion pressure distal to the stenosis. This results in the activation of the renin-angiotensin-aldosterone system, whereby renin is released from the juxtaglomerular apparatus, and a cascade of events occurs that ultimately leads to peripheral vasoconstriction, blood volume increase, and an elevation in blood pressure. Notably, renin converts angiotensinogen to angiotensin I and angiotensin I is then converted to angiotensin II through a process that requires ACE. In the kidney, angiotensin II results in the preferential constriction of efferent arterioles, which raises the pressure gradient across the glomerular capillary membrane and maintains the glomerular filtration rate (GFR). In patients with RVH, the administration of an ACEI blocks the conversion of angiotensin I to angiotensin II, thereby lowering the degree of vasoconstriction in the efferent arterioles, dropping the transcapillary pressures, and resulting in decreased GFR. There is also an increase in the creatinine level, which is the most common reason for pursuing a diagnosis of renal vascular disease. Decreased GFR can be assessed using nuclear scintigraphy and is the underlying mechanism for the diagnosis of RVH by ACEI scintigraphy.¹

TECHNICAL REQUIREMENTS

ACEI scintigraphy is performed with one head of a gamma camera. The field of view should include at least the kidneys and bladder. A large field of view camera is preferred so that the heart and blood pool clearance can be assessed. Ideally, continuous blood pressure monitoring should be performed and personnel trained in basic cardiopulmonary resuscitation should be immediately available in case of hypotension. An intravenous line can be placed for hydration, and should be used for those patients who are at high risk of cardiac disease and those receiving intravenous enalaprilat.

TECHNIQUES

Indications

ACEI renography can be used to assess for the presence of renovascular hypertension caused by renal artery stenosis. It is most cost-effective when used in a patient population with a high prevalence of RVH.² Many imaging modalities exist for the evaluation of renal artery stenosis, but renography may be particularly useful for those with known contrast allergy and in whom assessment of functional significance of a stenotic vessel is desired. The success of this technique is based on the inhibition of the conversion of angiotensin I to angiotensin II following the administration of an ACEI, with subsequent reduction in the GFR, and consequently a change in the radiopharmaceutical pattern of uptake and clearance in comparison to a baseline study.

Contraindications

Patients receiving an ACEI can experience significant hypotension; administration of an ACEI warrants proper clinical monitoring. Blood pressure should be carefully measured, with a baseline blood pressure established prior to the administration of the ACEI; subsequent blood pressure measurements should be performed at 5- to 15-minute intervals following drug administration and prior to discharge. Patients should not be discharged home unless their blood pressure is at least 70% of their baseline blood pressure. Chronic ACEI use can reduce the sensitivity of the study and a short-acting ACEI should be held for 3 days before the study and a longer acting ACEI should be held for 5 to 7 days. Chronic diuretic use may be associated with dehydration, leading to an increased risk of hypotension when the ACEI is administered; it should therefore be stopped a few days before the study. Calcium channel blockers have been reported to cause false-positive results and cessation prior to the study should also be considered.³ Many patients referred for this study will be at high risk for cardiovascular disease, however, and if hypertension is severe, antihypertensive use can be maintained with the understanding that there may be a mild reduction in the overall sensitivity of the study.

DESCRIPTION OF THE PROCEDURE

The initial patient screening should include a thorough patient history that includes listing of all medications and a review of any relevant imaging studies. Whenever possible, patients who have a history of chronic use of ACEI and diuretics should have these medications held prior to the study.

Oral captopril or intravenous enalaprilat may be used, although captopril is used more commonly. The oral captopril dose is 25 to 50 mg in adults, and 1 mg/kg in children, with a maximum dose of 50 mg. The captopril tablet is generally crushed and dissolved in water to ensure better gastric absorption. Peak systemic concentrations of captopril occur around 60 minutes after administration and then begin to decrease; therefore, the radiopharmaceutical is injected 60 minutes following captopril administration. Patients receiving oral captopril should avoid solid foods for at least 4 hours prior to administration to aid gastric absorption, although normal hydration should be continued.

Enalaprilat is administered intravenously over 3 to 5 minutes, with a dose of 40 µg/kg and a maximum dose of 2.5 mg. The radiopharmaceutical may be given 15 minutes following enalaprilat administration and the intravenous line should be maintained, because enalaprilat administration may be associated with more significant hypotension. The use of enalaprilat avoids the problem of uneven or incomplete gastric absorption, which could be an issue with captopril. In addition, the shorter waiting period prior to injection may also lead to a shorter study duration than when using oral captopril. Although enalaprilat and captopril are both thought to be suitable for the evaluation of RVH, enalaprilat is associated with a greater risk of hypotension. Captopril is generally more widely used and therefore will be discussed in this chapter.

Patients should be appropriately hydrated, because dehydration can affect renal perfusion curves.⁴ Patients with renin-dependent RVH may experience a drop in systolic blood pressure when the ACEI is administered, a drop that may be more severe if the patient is dehydrated. Hydration will also help decrease radiation dose to the bladder wall⁵ and to the surrounding reproductive organs by diluting the radioactivity in the bladder. Patients can receive oral or intravenous hydration, although intravenous hydration is generally preferred with enalaprilat. Oral hydration is generally 7 mg/kg of water and IV hydration, 10 mg/kg, with a maximum administered volume of 500 mL of normal saline over 30 minutes; both are initiated following ACEI administration.

A baseline blood pressure reading should be taken and recorded prior to administration of the medication. Four sequential blood pressure measurements are taken and recorded in the patient’s record at 15-minute intervals during the hour following captopril administration, prior to radiopharmaceutical administration. At the culmination of the study, a final blood pressure reading should be taken prior to discharge home. Patients receiving enalaprilat should have blood pressure measured every 5 minutes during the examination. The patient should void when the waiting period comes to an end, prior to imaging, because a full bladder may affect emptying of the upper tract ⁶ and could also lead to premature termination of the study if the patient needs to void during imaging.

The patient is then brought into the scan room and positioned supine on the imaging table with the camera located posteriorly to ensure that the kidneys are lying at the same depth, which could be affected with the patient semirecumbent or sitting.⁷ Once the patient is positioned appropriately, imaging begins with the intravenous injection of the radiopharmaceutical. The study should be dynamic, with the first series generally consisting of 1 sec/frame for 1 minute to assess early perfusion, the second series consisting of 5 sec/frame for 24 frames, and the final functional sequence, 30 sec/frame for 60 frames, for a total imaging time of approximately 30 minutes. The patient should void at the end of the study to reduce radiation dose to the kidneys, bladder, and pelvic organs. A postvoid bladder residual can also be calculated with a postvoid image consisting of a single 60-sec/frame image.

Dose infiltration can affect the results of the study. Correction for infiltration can be done by imaging the injection site and qualitatively or quantitatively assessing the injection dose. A quantitative evaluation is performed by determining the ratio of infiltrated counts to the original counts in the injected dose; with this method, syringe counts should be calculated prior to injection. A qualitative assessment is done visually. Assessment of a region of interest over the abdominal aorta during the immediate postinjection perfusion phase can also provide information about the quality of the injection bolus.

The study can be performed as either a 1- or 2-day protocol. The 1-day protocol requires the patient to visit the imaging department only once, but the length of time spent may be longer than with the 2-day protocol.

The 1-day protocol begins with a baseline study using a 1-mCi dose of radiopharmaceutical (37 MBq). This is followed by the ACEI-augmented study with a higher radionuclide dose of 5 to 10 mCi (185 to 370 MBq) to supersede any residual activity from the baseline study. It is helpful to obtain a single static postvoid image of the kidneys and bladder prior to the second injection of the radiopharmaceutical to assess how much, if any, residual activity remains, because residual activity could interfere with interpretation of the second imaging sequence.

Many departments begin the 2-day protocol with the ACEI-augmented study because a normal study will indicate a low likelihood of renovascular hypertension, obviating the need for the patient to return for a baseline determination. An abnormal augmented study will require the patient to return on a subsequent day for a baseline scan, at least 24 hours following the ACEI scan, to ensure that the baseline dose of technetium has decayed. Given this decay, both parts of the examination can be performed with 3 to 5 mCi (111 to 185 MBq) of the radiotracer, leading to better count statistics and better image resolution.

Following radiotracer injection, the loop diuretic furosemide may also be administered intravenously to clear radiotracer activity from the collecting system, reducing retention which could otherwise confound quantitative assessment.

Either technetium 99m mercaptoacetyltriglycine (^99mTc-MAG3), a tubularly secreted agent, or technetium 99m diethylenetriaminepentaacetic acid (^99mTc-DTPA), a glomerular agent, can be used for ACEI imaging. ^99mTc-MAG3 has a higher renal extraction rate and is therefore preferred by many institutions, particularly for patients with elevated creatinine levels. Iodohippurate sodium I 123 (¹²³I-OIH), also a tubularly secreted agent, can be used in a similar fashion, but is not commercially available in the United States or Canada.

PITFALLS AND SOLUTIONS

ACEI renography is best used in patients with normal or almost normal serum creatinine levels to ensure adequate renal concentration of the radiopharmaceutical. A poorly functioning kidney could lead to difficulty in interpretation because a kidney must be able to extract enough radiopharmaceutical to show a change in function when the ACEI is administered. ^99mTc-MAG3 has a higher renal extraction than ^99mTc-DTPA and is therefore preferred for patients with impaired renal function. Bilateral renal insufficiency can lead to a similar problem. Chronic administration of certain antihypertensives can reduce specificity of the examination and these medications may need to be held prior to the study.

IMAGE INTERPRETATION

Postprocessing

Whole renogram curves should be obtained over each kidney and cortical regions of interest (ROIs) can also be assessed to exclude any pelvocaliciceal tracer retention, which could interfere with study interpretation by introducing artificial counts into the calculations. Background subtraction should also be performed using a background ROI. Renal curves are generated from the renal ROIs and the time to maximum counts (T_max), as shown on the curves, is an important parameter in the diagnosis of RAS. Computer quantification can aid in interpretation and has been found to be useful in reducing false-positive results in patients with mildly abnormal perfusion at baseline.⁸

Reporting

The scintigraphic diagnosis of RAS is made when a change is seen on the ACEI-augmented scan from baseline. Diagnostic criteria will vary based on the radiotracer used. Decreases in GFR as a result of ACEI administration generally do not affect tubular uptake and secretion; therefore, initial tracer uptake is not affected with ^99mTc-MAG3 but will be affected with glomerularly secreted agents, such as ^99mTc-DTPA. With agents such as ^99mTc-DTPA, the main diagnostic finding with ACEI-augmented scans and RVH is an overall drop in function, although other findings such as delayed time to peak uptake, more than a 10% drop in differential function, and less than a 10% drop in GFR can also be seen. The most useful criterion for the diagnosis of RVH is unilateral cortical retention in the affected kidney, which can be seen with both agents, although more commonly with ^99mTc-MAG3.

Results from ACEI scintigraphy are reported as low, intermediate, or high probability for RAS (Fig. 108-1). A normal ACEI renogram indicates a low probability (less than 10%) of renal artery stenosis and these patients generally do not need further work-up for RVH or a baseline scan. A scan is read as having an intermediate probability for RVH when the baseline scan is abnormal but does not demonstrate change following the ACEI challenge. These patients generally are found to have ischemic nephropathy, often with a small shrunken kidney. ACEI -augmented scans are also read as intermediate probability in the face of bilateral cortical retention, as commonly seen with renal insufficiency, and in patients with only very small changes in function in relation to the baseline study. With both ^99mTc-DTPA and ^99mTc-MAG3, a change in differential function of greater than 10% is considered high probability for RAS, whereas a change from 5% to 9% is considered intermediate probability. Depending on the radiotracer, high-probability scans—those that demonstrate reductions in function, changes in differential function, delayed time to peak, and/or increased cortical retention—indicate a greater than 90% likelihood of RAS. These patients are likely to benefit from vascular intervention.

FIGURE 108-1 Positive captopril-augmented ^99mTc-MAG3 renal scintigraphy. A, The captopril study was performed first and revealed asymmetric renal function and bilateral cortical retention. B, A baseline scan shows continued renal asymmetry but with normalization of right renal function and a small change in the left. The left kidney was interpreted as indeterminate for RAS, and further work-up revealed it to be small in size. The right kidney was interpreted as having a high probability for RAS.

Bilateral cortical retention is more often caused by dehydration or a hypotension artifact rather than bilateral renal artery stenosis. Unilateral retention can be quantitatively assessed in several ways:

1 An increase in the 20/peak (ratio of cortical activity at 20 minutes to the amount of peak activity) or 20/3 ratio (count activity at 20 minutes divided by the activity at 3 minutes).

2 An increase of at least one grade in the renogram curve (Fig. 108-2). Renogram curves are scored from 0 to 4, with 0 reflecting a normal scan and thus a low probability of RVH, and 4 reflecting complete renal failure, with no extraction of the radiotracer, and thus a high probability of RVH. Grades 1 through 3 reflect progressive worsening from baseline, with increasing grade indicating more corresponding profound changes.

3 An increase in time to maximum parenchymal uptake (T_max) of at least 2 to 3 minutes.

4 A change of 10% or more in differential function, the amount each kidney contributes to overall function. This finding is less common with ^99mTc-MAG3 than with ^99mTc-DTPA. It is a significant finding and, when present, is considered high probability for RVH. A change of 5% to 9% is considered intermediate.

5 With ^99mTc-DTPA, a reduction in the glomerular filtration rate by 10% or more is also considered to be high probability for RVH.