Renal scintigraphy in infants and children

SOCIETY FOR FETAL UROLOGY UPDATE CME ARTICLE

RENAL SCINTIGRAPHY IN INFANTS AND CHILDREN GEORGE N. SFAKIANAKIS

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enal scintigraphy (with renography) is a test with unique scientific and logistic advantages when compared with other imaging methods, a “one-stop shopping” for evaluation of renal disorders (Table I). Renal scintigraphy, however, has limitations and is not always the ideal test (Table II). For certain deficiencies, scintigraphy is not indicated as the primary imaging modality for focal, strictly anatomic lesions such as tumors and cysts and certainly does not show renal calculi or calcifications. However, even in cases for which intravenous urography, ultrasonography, computed tomography, or magnetic resonance imaging may be the test of choice, scintigraphy may complement the other imaging modalities in reaching a definitive anatomic and functional diagnosis, such as obstruction, and it may evaluate the severity, provide functional follow-up information, and suggest the prognosis. On the basis of our experience, to fully and widely use the potentials of renal scintigraphy for the benefit of our patients, we propose, for all indications (Table III), a single, simple, and fast protocol using the best available radiopharmaceutical agent, mercapto-acetyl-triglycine or Mertiatide [MAG3].1 RADIOPHARMACEUTICAL AGENTS

Currently, several technetium-99m (99mTc)-labeled renal radiopharmaceuticals are in clinical use for imaging and renography, including glomerular (diethylenetriaminepentaacetic acid [DTPA]), cortical fixation (dimercapto-succinic-acid [DMSA], glucoheptonate [GH]) and tubular (MAG3) agents. Iodine (131I or 123I)-labeled I-o-hippurate-Na (HIP) is still used in some laboratories, although in most, this is gradually being replaced Presented at the Society for Fetal Urology biannual meeting, April 28, 2000, Atlanta, Georgia. From the Division of Nuclear Medicine, Department of Radiology, University of Miami/Jackson Memorial Medical Center, Miami, Florida Reprint requests: George N. Sfakianakis, M.D., Division of Nuclear Medicine (D-57), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101 Submitted: August 31, 2000, accepted (with revisions): February 26, 2001 © 2001, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED

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EFROSYNI SFAKIANAKI

by MAG3. Because of its favorable characteristics, MAG3 is the renal agent of choice and is used almost exclusively in our laboratory. It is the most costly after 123I-HIP, but the higher quality and exceptional diagnostic usefulness of the MAG3 studies justify the additional expenditure, especially in children and in parenchymal disorders not evaluated by other radiopharmaceutical agents.2,3 99m Tc-MAG3 is stored as a nonradioactive kit (triglycine, Betiatide) and as such has a long (more than 6 months) shelf life. After labeling with 99mTc (Mertiatide), it is stable for 6 hours. When injected, it circulates strongly protein bound, which allows only a small filtration rate (about 3% to 5% of what is presented to the glomeruli). MAG3 is mostly and actively accumulated and subsequently secreted by the proximal tubular cells (55% to 58%), and 40% of what is presented by the renal artery leaves the kidneys through the renal veins, with an overall 60% extraction rate. HIP has a higher extraction rate than MAG3 (80%); however, because of a smaller distribution space (MAG3 does not enter the erythrocytes and HIP does), MAG3 is excreted in the urine by the kidneys at a slightly higher rate than is HIP (73% versus 68% of the injected dose in 30 minutes). Clearance measurements (effective renal plasma flow [ERPF]) by blood sampling or computer counting after MAG3 injection are also comparable to HIP (after introducing a correction factor).4 Thus, MAG3 has the biologic properties of HIP and the physical imaging properties of a Tc-labeled agent and is used at much higher dosages than HIP, resulting in images that are of a better diagnostic quality than all the other radiopharmaceutical agents and in higher count rates for graph generation and quantitation. This advantage of MAG3 is most important in infants and children, particularly when renal function is decreased. It also increases the sensitivity and accuracy of the quantitation of function and drainage and provides diagnostic morphologic information.2,5 As a result, MAG3 can be used for all indications more efficiently than any other agent. To evaluate congenital disorders, MAG3 performs better than DTPA, allowing visualization of the kidney and quantitaUROLOGY 57: 1167–1177, 2001 • 0090-4295/01/$20.00 PII S0090-4295(01)01009-3 1167

TABLE I. Advantages of renal scintigraphy Provides useful, often unique, information in most clinical settings Combines information about regional and global kidney morphology and function Shows changes in renal blood flow, function, and intrarenal and extrarenal drainage Visualizes focal or diffuse functional lesions no other modality can show Useful for congenital or acquired disorders and for complications of renal transplants Applicable in patients of all ages and in all renal functional states, including renal failure Contributes to diagnosis, prognosis for recovery, and follow-up treatment or disease Technically easy Only hydration and immobilization is needed—no sedation or other preparation Urinary bladder catheterization is not required (only exceptionally) Drains, dressing, wounds, bowel gas, tubes, and metals do not interfere Available for emergencies and at bedside, emergency or operating rooms Easy to perform after short-term training of technical personnel Not operator dependent, as compared with sonography Safe, acceptable, and affordable Reactions to radiopharmaceutical agents are extremely rare and mild in intensity Well accepted by patients (except for venipuncture, catheterization) Radiation exposure is low (less than with some radiographic studies, such as intravenous urography) Actual cost is in the lower range of imaging procedures

TABLE II. Limitations of renal scintigraphy Limitations Limited resolution (0.5–1.0 cm) for anatomic lesions (tumors, cysts) Larger cysts or tumors (visible as fixed defect) are difficult to differentiate Does not detect calcification and stones Other imaging modalities are needed to provide complementary information Complex and unnecessary length of scintigraphic protocols in many laboratories Choice of too many radiopharmaceutical agents confusing to technologists and doctors Lack of familiarity among referring physicians and users of many indications/interpretations Underuse of renal scintigraphy in many centers because of previous two limitations Unjustified fear of radiation side effects by patients, personnel, doctors Proposed solution A simple protocol for all indications: one radiopharmaceutical agent and a 25-minute study—MAG3-F0 Education of referring and user doctors about indications and interpretation of MAG3-F0 study KEY: MAG3-F0 ⫽ 99mTc-MAG3 with furosemide at zero time.

tion of renal function when DTPA does not provide sufficient information. Because of its tubular nature, MAG3 shows diffuse or focal tubular dysfunction with clarity and reproducibility unsurpassed by any other agent.2,6 Unlike DMSA, which is a cortical fixation agent (and GH, which is also to a smaller extent), MAG3 has no cortical fixation and, when nonactive small cortical lesions are sought, DMSA multiprojectional pinhole or tomographic images (single photon emission computed tomography [SPECT]) have been used with good results. However, SPECT MAG3 is feasible with three-detector cameras and may provide results equivalent to DMSA within minutes, instead of hours of waiting before imaging, which is necessary when DMSA or GH is used to allow background clearing from the circulating radiopharmaceuticals.7 A characteristic example of using MAG3 instead 1168

of DMSA or GH is for the diagnosis of acute pyelonephritis (APN). APN is characterized by cortical defects on DMSA/GH that are difficult to differentiate from old scars or space-occupying lesions; MAG3 generates more convincing images in APN because of focal cortical retention of activity or focal dysfunction, which is usually more extensive than the minute defects of DMSA, is more easily detectable, faster (within 25 minutes), and results in lower radiation exposure.6,8 MAG3 is recommended in a graduated dose of 10 mCi; for SPECT, the dose may be doubled. DTPA may be used in a dose of 10 to 20 mCi, DMSA at a dose of 5 mCi, GH at a dose of 10 to 20 mCi, 131 I-HIP at a dose of 300 ␮Ci, and 123I-HIP at a dose of 250 to 500 ␮Ci. The minimum pediatric doses are 0.5 to 1 mCi of MAG3, DTPA, GH; 0.5 mCi of DMSA; and 50 ␮Ci of HIP. The radiation exposure for the total body, kidneys, and bladder is UROLOGY 57 (6), 2001

TABLE III. Most common indications for renal scintigraphy Neonates Congenital renal insufficiency/failure (bilateral renal disorders) Perinatal complications (acute tubular necrosis, trauma, renovascular hypertension) Workup of perinatal ultrasonographic findings (congenital renal anomalies) Masses in the abdomen (usually associated with sonographic findings) Search for, and evaluation of, congenital renal anomalies in patients with other stigmata Children, adolescents, and adults Workup of ultrasonographic findings (congenital renal anomalies) Workup of congenital or acquired renal obstruction (renal colic, calculi, strictures, tumors) Etiology of decreased renal function (acute vs. chronic, parenchymal vs. obstruction) Evaluation of patients with urinary tract infections (acute pyelonephritis, scars, other abnormalities) Evaluation of parenchymal renal disorders (acute tubular necrosis, nephritic, nephrotic, nephrotoxicity) Evaluation of renovascular disorders (artery/vein) and diagnosis of renovascular hypertension Workup of patients with vesicoureteral reflux to evaluate effect on renal anatomy/function Complementary information in trauma, hematuria, tumors, cysts, others Short-term and long-term follow-up of effects of disease/treatment on renal anatomy/function In general, complementary information on diagnosis, function, follow-up, and prognosis for recovery Evaluation of renal allograft anatomic or parenchymal complications

lower for MAG3 when injected simultaneously with furosemide.7 GENERAL ROUTINE PROTOCOL OF DIURETIC RENAL SCINTIGRAPHY AT UNIVERSITY OF MIAMI/JACKSON MEMORIAL MEDICAL CENTER PATIENT PREPARATION Although a supine position is acceptable, in adults an upright position is preferred for better gravity-assisted drainage of the kidneys when the potential diagnosis is obstruction. Patient immobilization is essential, and in infants and children, the use of a papoose board is mandatory. The patient should be well hydrated unless contraindicated (10 mL/kg water or juice orally 30 minutes before imaging or intravenous saline or dextrose/saline 100 to 500 mL starting 30 minutes before imaging and continuing during the study). The patient should be calm and comfortable, in a warm environment. When children are examined, the parent should be present. Before injection, the absence of extravasation should be verified by infusion of 2 to 5 mL normal saline. Sedation may be administered only if absolutely needed. Adults should be informed and periodically reminded to stay still. We do not use bladder catheterization, especially in infants who normally void 10 minutes after diuretic administration. When intrarenal or ureteral obstruction is to be excluded, and bladder or urethral abnormalities are present or suspected, urinary bladder drainage (Foley catheter in place) may be indicated, because a full bladder may induce retention of the radiopharmaceutical agent proximally, suggesting obstruction. The same may be true when seeking accurate cortical transit times UROLOGY 57 (6), 2001

of radiopharmaceuticals in the investigation of renovascular hypertension (RVH). Brief Outline of Protocol. Dynamic renal scintigraphy is performed in the posterior projection (in patients with transplants, anteriorly) sequentially for 22 minutes after a bolus intravenous injection of 1 to 10 mCi MAG3 followed immediately (zero time) by an intravenous diuretic, such as furosemide (MAG3-F0), using high-efficiency parallelhole collimators. The study is completed after a postvoid (after holding infants upright) static image; when indicated, delayed static images may complement the dynamic study.1 Diuretic Use. At 20 minutes after injection of MAG3, in a well-hydrated patient, the intrarenal drainage system and ureters should empty normally, with only a slight amount of tracer visible. Postural pooling can be ruled out by obtaining the postvoid or post-upright image described above. However, even after good hydration, images may mimic obstruction because of inadequate diuresis; this happens quite frequently when the drainage system is wider than average and raises the question of obstruction. The administration of a diuretic at the time of injection of MAG3 alleviates confusing images of the cortices or questionable retention within the drainage system. A diuretic that does not affect the tested function of the kidney should be used, such as the loop diuretic furosemide (Lasix 1 mg/kg, maximum 40 mg or 80 mg in the presence of renal insufficiency when creatinine is greater than 1.8 mg/dL). Injection of the diuretic simultaneously with the radiopharmaceutical (furosemide at 0 time [F0]) allows peak diuretic action in less than 10 minutes. With a protocol of 22 minutes, the time to observe the diuretic effect and exclude obstruction is am1169

ple. Therefore, this approach is one of the three choices for diuretic renography.1,5,9,10 In addition, it provides more reliable cortical images and data for the quantitation of the cortical function in the presence of disease2 and after pharmacologic intervention.11 It also empties the unobstructed drainage system (unless function is severely diminished), thus completing a diuretic examination in 25 minutes. Finally, by promoting frequent urination, this method decreases the radiation exposure to the urinary bladder.7 For all these reasons, we use a diuretic with all indications and in all patients who undergo renal scintigraphy. No complications from the diuretic have been observed for 10 years with more than 1500 studies yearly. Imaging Protocol. The sequential imaging starts as a 60-second flow phase (1-second frames for graphs and 3-second images) and continues as a 22-minute tissue-function/drainage phase (30-second frames for renograms and 2-minute images). After this phase, the patient assumes the upright position and empties the bladder. Infants are held upright for a few minutes. Then, a postvoid image is acquired with the same settings as for the tissue phase; if activity remains in the kidneys or the ureters, a similar image is taken at 1 to 2 hours after injection. Time Activity Graph Generation, Analysis, Quantitation. Time-activity graphs of both the flow (perfusion graphs) and the 22-minute tissue phase (renograms) of the total kidney, including the renal pelvis and of the cortex exclusively, are generated. A simple routine makes two composite 30second images from the 60 1-second flow frames and places them before the frames of the tissue phase for more complete renograms. It is imperative to select as cortical regions of interest those that do not include collecting system activity at any time, and it is equally important to include the entire renal pelvis in the region of interest of the total kidney. Although the selection of background for correction should ideally be circular around the kidney, regions below and lateral to the kidney are usually acceptable. Patient motion should be prevented or corrected by special programs. Renograms thus generated can then be reliable for cortical and/or drainage abnormalities and may be analyzed semiquantitatively. Estimation of Split Renal Function. Information on the function of one kidney compared with the other (split renal function [SRF]) is often clinically useful, particularly when nephrectomy or corrective intervention is contemplated. Baseline and follow-up information is essential for measuring the effect of surgical intervention or the progression of the disorder. SRF can be calculated with scintigraphy. There are three techniques: (a) quantitation of the net radioactivity present in the kidneys at 1 to 2 1170

minutes after injection of MAG3, DTPA, GH, or HIP and before activity enters the ureters, (b) quantitation of cortical activity on planar imaging with DMSA at 3 to 4 hours, after the intrarenal collecting systems are emptied, from posterior views only, or, better, from posterior and anterior images using the geometric mean of these counts, and (c) quantitation of renal activity after SPECT imaging (at 1 to 2 minutes after injection with MAG3 and at 3 to 4 hours after DMSA administration).7 In ectopia and severe hydronephrosis with markedly compromised function, especially in the infant, accurate quantitation of SRF is a challenge because the 1 to 2-minute results during dynamic planar imaging (a, above) are often not reliable; for better results, either measurement at later times (2, 3, or 4 minutes), adding if needed, the activity of the bladder for the healthy kidney, or the above b or c approaches are needed. SCINTIGRAPHY IN CONGENITAL OR ACQUIRED OBSTRUCTION OF THE DRAINAGE SYSTEM Dilation of the Drainage System and Obstruction. The most common feature of drainage system anomalies is dilation. When associated with obstruction, the term “hydronephrosis” is used to describe the dilated renal pelvis and “hydroureter” for the dilated obstructed ureter; “caliectasis,” “pelviectasis,” and “megaureter” denote dilation but not necessarily obstruction.12 When in doubt, “obstructive” can be added to further clarify the meaning. A dilated intrarenal collecting system may be associated with (a) a larger appearing kidney, (b) one that is of an overall normal size, or even (c) a smaller kidney (relative dilation). Except in the case of an uncomplicated extrarenal pelvis, a dilated intrarenal drainage system is associated with parenchymal thinning of varying severity, depending on the degree and duration of the causative agent (eg, obstruction, reflux, neurogenic problem). Although scintigraphy may not provide precise measurements, MAG3-F0 scintigraphy can effectively identify the size of the kidney and also the existence of parenchymal thinning (Figs. 1 to 3). Urinary tract anatomic obstruction with resultant hydronephrosis is usually congenital in a child (ureteropelvic junction, ureterovesical junction, ectopic ureters, posterior urethral valves), but it is usually acquired in an adult (stones, tumors, clots, fungal balls, bladder and urethral pathologic features, retroperitoneal fibrosis and, less frequently, after trauma or surgery). Congenital or acquired functional abnormalities of the bladder (neurogenic bladder in myelomeningocele or spinal cord injury) eventually result in functional obstruction. Vesicoureteral reflux and primary megaureter (adynamic distal ureter) may also be considered UROLOGY 57 (6), 2001

FIGURE 1. Downsloping MAG3-F0 renography predicting spontaneous recovery. (A) MAG3-F0 in a newborn infant (5 days old) with congenital unilateral (right) pelvocaliectasis by prenatal ultrasonography. There is retention within the intrarenal collecting system of the right kidney. The renogram of the right kidney is abnormal, but downsloping predicts a spontaneous resolution. The SRF was 45% in the left kidney and 55% in the right. (B) Indeed, 6 months later, the repeated study showed nearly complete resolution of the abnormality. The SRF was 50% in the left kidney and 50% in the right. All images are posterior views, in 2-minute intervals; the actual time of acquisition is written underneath them. The renograms are those of the entire kidneys, including the pelvis; the darker colored renogram is that of the left kidney.

forms of functional obstruction, resulting in pelviectasis and caliectasis. When obstruction is complete, no flow of urine is possible. Complete obstruction results in agenesis or UROLOGY 57 (6), 2001

dysplasia in the fetus and only partial obstruction is seen with a functioning kidney in the infant or child. Complete obstruction from stones or clots is a not unusual finding in the adult, and with MAG3-F0 renal 1171

FIGURE 2. Upsloping MAG3-F0 renography predicting the need for intervention. (A) MAG3-F0 in a newborn infant (5 days old) with congenital unilateral pelvocaliectasis by prenatal ultrasonography. There is retention within the intrarenal collecting system of the left kidney. The renogram is rising, predicting the need for intervention. The SRF was 50% in the left kidney and 50% in the right. (B) Indeed, 1 month later, associated with deterioration by ultrasound scanning, a persistent abnormality and interval loss of function was noted. The SRF was 31% in the left kidney and 69% in the right. Surgical intervention (pyeloplasty) was soon performed, but, as a follow-up MAG3-F0 indicated (not shown), the SRF did not improve, despite normalization of the drainage.

scintigraphy, cortical activity will be decreased but always present and rising over time; however, no radionuclide activity will be present at any time in the collecting system and the level of the obstruction will not be evident.5 In contrast, when the obstruction is partial, the drainage system fills late and retains the 1172

activity (stasis) at the level of obstruction and proximally, given sufficient time for the radioactive urine to reach that point.5 Acute obstruction may not be associated with dilation of the drainage system; however, older, or chronic obstruction is characterized by dilation. The UROLOGY 57 (6), 2001

FIGURE 3. Early surgical decompression helps recapture renal function. (A) Newborn infant (2 days old) with bilateral ureteropelvic junction stenosis, much more severe on the left side as shown by MAG3-F0. On the left, very severe hydronephrosis was present with only the upper pole showing prompt function; slow filling of the extremely dilated drainage system is evident; the renogram is rising. The right kidney was also abnormal but with a downsloping renogram. The SRF was 11% in the left kidney and 89% in the right. Because of the bilateral pathologic findings, the more seriously impaired kidney (left) was decompressed at age 5 days. (B) Follow-up MAG3-F0 study at age 2.5 months indicating unchanged abnormality of the right kidney, but improving drainage, size, and renal function of the left kidney. The SRF was 44% in the left kidney and 56% in the right.

degree of renal function impairment and also of parenchymal thinning and stasis are directly proportional to the severity and duration of the obstruction.5 Scintigraphic images in any type of obstruction UROLOGY 57 (6), 2001

show markedly decreased renal blood flow, decreased and delayed accumulation, and retention of activity in the parenchyma and (in partial obstruction) the drainage system; these findings are associated with abnormal renograms. However, 1173

delayed excretion and retention of urine may also be seen in normal kidneys, or it may be the result of any parenchymal dysfunction. In addition, in acute obstruction, hydronephrosis might not yet have occurred. Moreover, a dilated collecting system may not be due to current but, rather, to old obstruction. Therefore, diuretic renography is essential to identify and characterize the obstruction in many clinical settings. In the process of interpreting such a study, it is, of course, necessary to consider and evaluate the role of the parenchyma (visually and by cortical renography), the intrarenal collecting system (visually and by total kidney renography), and the ureters and bladder. Diuresis induces fast emptying of the unobstructed kidney but has little effect on the obstructed kidney; however, when cortical function is reduced, the diuretic might not be effective in emptying the drainage system even with a double dose, which is recommended in renal insufficiency. In these cases, uncertainty remains and more invasive procedures may be justified, such as intravenous urography, retrograde pyelography, Whitaker test, stenting, or even nephrostomy. Finally, special emphasis should be placed on the pattern of the renal cortical activity and the corresponding renograms. If these are normal, obstruction is not present, even in cases with high intensity pelvic retention, such as in residual postdecompression pelvicaliectasis and in certain cases of extrarenal pelvis with ureteropelvic junction stenosis and dilation. Diuretic Renography Protocol. Diuretic renography1,5,9 is useful in confirming or excluding obstruction. The use of intravenous furosemide is recommended by various investigators to be administered either 15 minutes before (F⫺15), coincidentally with (F0), or 20 minutes after (F⫹20) the injection of a radiopharmaceutical agent. More recently, MAG3 has been the most frequently used radiopharmaceutical agent for diuretic renography.10 We use the F0 approach and MAG3 with results comparable to the other time schedules when function is substantially preserved.9 The dose is 1 mg/kg, maximum 40 mg. For creatinine greater than 1.8 mg/dL, the dose is doubled. The general simple routine protocol described above is used as diuretic renography in our centers. More involved and lengthy protocols have been proposed,13 but they fail to provide more accurate results.9 The criterion for obstruction for F0 or F⫺15 is a half-time of total renal activity (including the collecting system) of greater than 15 minutes from the injection of radiopharmaceutical agent; for F⫹20, obstruction is reported when the halftime from the time of injection of furosemide exceeds 20 minutes, with an acceptable range between 10 and 20 minutes. When function is 1174

substantially reduced, the results are questionable for all the methods. The evaluation of cortical activity is of considerable help in unilateral disorders; if it is similar to the contralateral kidney, obstruction is unlikely. In the newborn infant with immature kidneys, the above criteria do not apply. In this report, evidence is provided that only rising renograms may reliably indicate obstruction at this age14 (see the section Scintigraphy in the Neonate). Although frequently practiced in hospital settings, the use of bladder catheterization is an invasive procedure both physically and psychologically and, particularly when obstruction is present, carries a danger of infection (albeit small when performed by trained personnel). As such, we do not routinely practice diuretic renography with a catheter in place. The use of a bladder catheter is reserved only for selected cases, such as patients with neurogenic bladder, reflux, or severely diminished function, for patients with questionable obstruction studied repeatedly, or postoperatively in patients with suspicion of persistent obstruction. INDICATIONS FOR RENAL SCINTIGRAPHY MAG3-F0 renal scintigraphy provides useful diagnostic, prognostic, and baseline and follow-up information for most congenital or acquired disorders from the neonate to geriatric patient for the native kidneys or renal tomography.3,15–18 (Table III). SCINTIGRAPHY IN THE NEONATE The usual presentation is prenatal or postnatal ultrasonographic findings and, less frequently, renal insufficiency or failure (oliguria, anuria, laboratory results). Abdominal masses or workup for congenital malformations are currently infrequent indications. In all such conditions, scintigraphy provides correlative information for the investigation of the genitourinary problem. It helps differentiate congenital from perinatal renal diseases and confirm the existence, location, parenchymal quality (function), and drainage of the kidneys and establishes the diagnosis of a congenital abnormality and the need for corrective intervention. Furthermore, it establishes a baseline functional profile and provides prognostic information for the abnormal kidney. PERINATAL PROBLEMS Renal Insufficiency/Failure. In such a presentation, scintigraphy will differentiate between bilateral congenital anomalies (dysplastic or obstructive) and perinatal events (eg, ischemia, acute tubular necrosis [ATN], dehydration).15,16,19 Neonatal Hypertension. Due mostly to renal ischemia from aortic thrombus (a complication of umUROLOGY 57 (6), 2001

bilical artery catheterization), neonatal hypertension can effectively be studied with MAG3 baseline and angiotensin-converting enzyme (ACE) inhibition scintigraphy (see below).15,16,19 The results of the test can indicate the need for special therapy (ie, to avoid the use of ACE inhibitors to prevent renal failure).19 CONGENITAL RENAL ANOMALIES Scintigraphy helps establish the correct and accurate diagnosis in most congenital renal anomalies, indicates the current functional state of the individual kidneys, provides prognostic information, and can be used for decision making about intervention.14 –16 Dysplasias. The lack of function (no visualization-photopenic defect) helps confirm the diagnosis of the multicystic dysplastic kidney and differentiate it from severe obstructive disorders (which will demonstrate some function). The characteristic image of the polycystic kidneys (large, hypofunctioning, but draining) helps to reach such a diagnosis. Dysplasias without cystic components can also be diagnosed by scintigraphy, as they are identified by a decrease in accumulation and discharge of the radiopharmaceutical agent and by quantitative renography. Ectopias. That the entire abdomen and pelvis are thoroughly and continuously evaluated by scintigraphy makes this test the most reliable for identifying ectopic units and fusions and for establishing the normal or abnormal function of these kidneys. Most useful is the first 2-minute image during MAG3-F0, which shows the ectopic parenchyma before active urine obscures the background of the pelvis. Obstructive Disorders. Scintigraphy is the ideal method for the evaluation of obstructive disorders. The patients usually present with only ultrasonographic findings, unless the disorder (a) is bilateral, (b) associated with contralateral dysplasia, or (c) is due to bladder outlet obstruction or posterior urethral valves. In these cases, the global renal function may be reduced in addition to morphologic findings (ie, anuria, oliguria, abnormal blood urea nitrogen, abnormal creatinine clearance). An obstructed kidney exhibits a functioning cortex and delayed filling and then a persistently active drainage system. MAG3-F0 scintigraphy in most cases will exclude or confirm the correct diagnosis of obstruction, whether unilateral or bilateral, and will indicate the individual kidney’s current contribution to actual renal function and the reserves that an obstructed kidney possesses. Scintigraphy may also indicate the need for surgical correction. UROLOGY 57 (6), 2001

VALUE OF MAG3-F0 DIURETIC RENOGRAPHY IN PREDICTING NEED FOR SURGERY IN NEONATES WITH URETEROPELVIC JUNCTION OBSTRUCTION The predictive value of diuretic MAG3-F0 scintigraphic renography was studied prospectively at our center in more than 100 neonates with sonographic hydronephrosis. The hypothesis was that in neonates with evidence of severe obstruction, as indicated by MAG3-F0, surgical decompression (eg, pyeloplasty) is needed but that mild retention in a dilated system would be self-eliminated. Results are currently available in more than 35 patients. MAG3-F0 was performed without a bladder catheter (all patients emptied their bladders spontaneously) after an intravenous injection of 1 mCi 99m Tc-Mertiatide (MAG3) followed immediately by 1 mg/kg furosemide (F0), as discussed above. The morphology of the kidneys, the shape of the renograms, and the residual kidney activity at 20 minutes (RKA) was noted. The normal pattern was studied in more than 50 neonates without hydronephrosis and was consistent with a downsloping graph after peaking at 2 to 4 minutes, with an RKA of less than 50% of the peak value. A retrospective analysis of the data indicated that, as reviewed so far, among 35 neonates with grade II or higher hydronephrosis by ultrasound scan, 18 underwent surgery, and 17 were followed up until their anatomy and function stabilized and satisfactory drainage was established. Surgery was decided on the basis of a number of parameters (decreasing function, thinning parenchyma, deteriorating hydronephrosis, including dilated calices, condition of the contralateral kidney, etc.). Three patterns of MAG3-F0 results were obtained: (a) category 1, with a downsloping renogram and RKA (at 20 minutes) greater than 50% but less than 80% of the peak value and no significant impairment of renal function (Fig. 1); (b) category 2, with a renogram reaching a plateau and RKA between 80% and 100% of the peak value and mild impairment of renal function (25% ⬍ SRF ⬍ 30%); and (c) category 3, with a rising renogram and moderate to severe impairment of renal function (SRF less than 30%) (Fig. 2). None of the 15 patients in category 1 required surgery. All 14 patients in category 3 required surgery. Four patients in category 2 required surgery, and two did not. In addition, earlier intervention appeared to enhance the improvement in renal function (Fig. 3). The available data indicate that diuretic MAG3 in the neonate with simultaneous injection of Lasix (MAG3-F0) has a predictive value for the need of surgery and may be used to decide earlier and, potentially, more effective intervention.14 1175

OTHER METHODS FOR PREDICTING THE NEED FOR SURGERY The use of ACE inhibition scintigraphy to determine the need for decompression in congenital obstruction has recently been proposed and may prove to be a reliable method. It has been suggested that obstruction may activate the renin-angiotensin system, thus allowing use of ACE inhibition to determine such conditions (see the next section Renal Artery Stenosis and Renal Ischemia) and indirectly the existence of obstruction. Work is currently underway at some institutions. RENAL ARTERY STENOSIS AND RENAL ISCHEMIA EVALUATION OF INFANTS AND CHILDREN WITH HYPERTENSION: RVH AND ACE INHIBITION SCINTIGRAPHY Severe renal ischemia due to more than critical renal artery or branch stenosis in the child or adult, or to complications (thrombus) of umbilical artery catheterization in the neonate, leads to RVH. RVH is due to oversecretion of renin and overproduction of angiotensin II, which depends on angiotensinogen-angiotensin I and angiotensin I-converting enzyme or ACE. Angiotensin II compensates the glomerular filtration rate locally but, since ischemia persists, angiotensin II is continuously hyperproduced and with its peripheral action induces RVH. ACE inhibitors control RVH but decompensate renal function. All the above are reliably detected by baseline and ACE inhibition MAG3-F0 renal scintigraphy, which accurately indicates the diagnosis of RVH.11,19 –21 CURRENT PROTOCOL FOR RVH We currently use a 1-hour protocol to acquire a complete study.11,19 After hydration, and with the patient not receiving (3 days) ACE inhibition, a 22-minute baseline study with 0.1 to 1 mCi MAG3 is performed; it is followed 10 minutes later by 0.04 mg/kg (maximum 2.5 mg) intravenous enalaprilat (Vasotec) administration and after another 10 minutes, repeated scintigraphy with 1 to 9 mCi MAG3. Each time, furosemide 0.5 mg/kg (maximum 20 mg or 40 mg if the creatinine is greater than 1.8 mg/dL) is injected with the MAG3. Oral captopril (Capoten) may be used, instead of enalaprilat, in a dose of 0.2 to 0.4 mg/kg (maximum 50 mg), with a 1-hour waiting period. A positive study will reveal a deterioration of renal function as 10% or greater increased RKA from baseline if compensation is present. In extremely severe stenosis, without compensation, a rising renogram will be present at baseline and ACE inhibition will have little effect. In arterial obstruction, the kidney is not functioning but may still be 1176

alive and inducing RVH, in which case scintigraphy will show a lack of function.19 –21 EVALUATION OF RENAL PARENCHYMAL DISORDERS ACUTE PYELONEPHRITIS The potential use of planar dynamic MAG3 scintigraphy for investigation of the renal parenchyma in patients with urinary tract infection has been evaluated by various investigators. Varying results were reported in different studies. In our experience, focal regional late retention of MAG3 activity is a highly sensitive and specific indication of APN, at least as good as DMSA findings.6 The lack of three-dimensional information appears to occasionally have a negative effect on the specificity of planar MAG3 dynamic imaging in the investigation of focal lesions of the renal parenchyma. This prompted the evaluation of MAG3 for SPECT studies, which indicated its usefulness, not only for APN but also for small scars, ectopias, and other pathologic findings.7 ACUTE TUBULAR NECROSIS ATN is characterized by diffuse parenchymal disease (decreased uptake and long retention of MAG3) but with a relatively preserved renal blood flow. The pattern is similar in native kidneys and in transplants. It has been seen in children and adults after ischemic insults to the kidneys and in the neonate with perinatal renal ischemia. ATN results in decreased function, which needs appropriate workup. The diagnosis is indicated by MAG3-F0 scintigraphy, which typically demonstrates a more severe renal function impairment and a relative preservation of blood flow.3 In the neonate, ATN needs to be differentiated from immaturity and dysplasia by quantitation (renograms). DIFFUSE RENAL PARENCHYMAL DISORDERS MAG3-F0 may be useful in the evaluation of diffuse renal parenchymal disorders (eg, human immunodeficiency virus nephropathy-lupus and other nephrotic syndromes) because of its high sensitivity and quantitative abilities.2 ACQUIRED RENAL OBSTRUCTION MAG3-F0 is the agent of choice to differentiate acquired obstruction from other causes of renal insufficiency, to determine whether a dilated system is currently obstructed, and to determine whether patients with colic indeed have obstruction.5 UROLOGY 57 (6), 2001

OTHER RENAL PATHOLOGIC FEATURES Renal artery or vein obstruction may be evaluated by renal scintigraphy. The lack of function (artery obstruction) or a focal wedge-shaped defect (infarct from branch obstruction) are the results of acute or old arterial obstruction. Renal vein thrombosis has variable appearance depending on the age (destruction of the kidney in the neonate/infant and preservation of function with potential collateral development or recanalization later in the child and adult).15–17,22 MAG3-F0 provides very sensitive diagnostic images in renal trauma, especially when urine is extravasated. However, computed tomography and sonography are used for abdominal trauma to show trauma of organs other than the kidneys simultaneously. MAG3-F0 is not indicated for spaceoccupying lesions unless functional information is needed (eg, split renal function). In all the above conditions, MAG3-F0 may provide useful complementary functional information.17 EVALUATION OF COMPLICATIONS OF RENAL TRANSPLANTS MAG3-F0 is very helpful when the patient with renal transplant is admitted because of deterioration of renal function.18 It indicates or excludes anatomic complications (eg, RAS, RVT, obstruction, leaks, APN, scars, infarcts) and provides quantitative information about diffuse functional complications (acute or chronic rejection, toxicity, recurrence of primary renal disease, etc.). It may differentiate these conditions from ATN by using renal flow and function comparisons.3,21 CONCLUSIONS MAG3-F0 is a safe, simple, and fast protocol that provides valuable information in all renal clinical conditions, from the neonatal to the geriatric period. REFERENCES 1. Sfakianakis GN, Georgiou MS, Cavagnaro F, et al: Fast protocols for obstruction (diuretic renography) and for renovascular hypertension (ACE-inhibition). J Nucl Med Technol 20: 193–206, 1992. 2. Sfakianakis GN, Carmona AJ, Sharma A, et al: Diuretic MAG3 scintirenography in children with HIV nephropathy: diffuse parenchymal dysfunction. J Nucl Med 41: 1037–1042, 2000. 3. Sfakianakis GN, Tapia-Palacios M, Gomez-Marin O, et al: MAG3 scintirenography to differentiate ATN, rejection, and nephrotoxicity in renal transplants (abstract). J Nucl Med 40: 93P, 1999. 4. Taylor A, Corrigan PL, Galt J, et al: Measuring techne-

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tium-99m-MAG3 clearance with an improved camera-based method. J Nucl Med 36: 1689 –1695, 1995. 5. Sfakianakis GN, Cohen DJ, Braunstein RH, et al: MAG3-F0 scintigraphy in decision making for emergency intervention in renal colic after helical CT positive for a urolith. J Nucl Med 41: 1813–1822, 2000. 6. Sfakianakis GN, Cavagnaro F, Zilleruelo G, et al: Diuretic MAG3 scintigraphy (F0) in acute pyelonephritis: the regional parenchymal dysfunction and comparison with DMSA. J Nucl Med 41: 1955–1963, 2000. 7. Sfakianakis GN, and Georgiou MF: MAG3 SPECT: a rapid procedure to evaluate the renal parenchyma. J Nucl Med 38: 478 – 483, 1997. 8. Sfakianakis GN, Zilleruelo G, Cavagnaro F, et al: A prospective comparative DMSA and MAG3 study in acute pyelonephritis, in Taylor A, Nally JV, and Thompson H (Eds): Radionuclides in Nephrourology. Reston, Virginia, Society of Nuclear Medicine, 1997, pp 182–184. 9. Sfakianakis GN, Cole C, Georgiou MF, et al: Optimal timing of diuretic administration in diuretic renography (abstract). J Nucl Med 40: 51P, 1999. 10. O’Reilly P, Aurell M, Britton K, et al: Consensus for diuresis renography for investigating the dilated upper urinary tract (Paper on Obstruction). J Nucl Med 37: 1872–1876, 1996. 11. Sfakianakis GN, Bourgoignie JJ, Georgiou MF, et al: Diagnosis of renovascular hypertension with ACE-inhibition scintigraphy. Radiol Clin North Am 31: 831– 848, 1993. 12. Dorland’s Illustrated Medical Dictionary, 24th ed. Philadelphia, WB Saunders, 1965. 13. Members of the Society of Fetal Urology and Pediatric Nuclear Medicine Council Members, Society of Nuclear Medicine: The “well tempered” diuretic renogram: a standard method to examine the asymptomatic neonate with hydronephrosis or hydroureteronephrosis. J Nucl Med 33: 2047–2051, 1992. 14. Sfakianakis GN, Zilleruelo G, Thompson T, et al: Tc99m-glucoheptonate scintigraphy in a case of renal vein thrombosis. Clin Nucl Med 10: 75–79, 1985. 15. Sfakianakis GN, and Damoulaki-Sfakianaki E: Nuclear medicine in pediatric urology and nephrology. J Nucl Med 29: 1287–1300, 1988. 16. Sfakianakis GN: Nuclear medicine in congenital urinary tract anomalies, in Freeman LM (Ed): Nuclear Medicine Annual. New York, Raven Press, 1991, pp 129 –160. 17. Sfakianakis GN, Vonorta K, Zilleruelo G, et al: Scintigraphy in acquired renal disorders, in Freeman LM (Ed): Nuclear Medicine Annual. New York, Raven Press, 1992, pp 157– 224. 18. Dubovsky EV, and Russell CD: Radionuclide evaluation of renal transplants, in Blaufox MD (Ed): Evaluation of Renal Function and Disease with Nuclides: The Upper Urinary Tract. Basel, S. Karger, 1989, pp 373– 412. 19. Chandar JJ, Sfakianakis GN, Zilleruelo GE, et al: ACEinhibition scintigraphy in the management of hypertension in children. Pediatr Nephrol 13: 493–500, 1999. 20. Taylor A, Nally J, Aurell M, et al: Consensus report on ACE-inhibitor scintigraphy for detecting renovascular hypertension. J Nucl Med 37: 1876 –1882, 1996. 21. Sfakianakis GN, Bourgoignie JJ, Jaffe D, et al: Singledose captopril scintigraphy in the diagnosis of renovascular hypertension. J Nucl Med 28: 1383–1392, 1987. 22. Sfakianakis GN, Zilleruelo G, Thompson T, et al: Tc99m-glucoheptonate scintigraphy in a case of renal vein thrombosis. Clin Nucl Med 10: 75–79, 1985.

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