Urol Radiol 14:85-95 (1992)

Urologic Radiology © Springer-VedagNewYorkInc.1992

Nuclear Medicine Evaluation of Hypertension Eugene J. Fine Department of Nuclear Medicine, Bronx Municipal Hospital Center, Bronx, New York, USA

Abstract. Noninvasive diagnosis of renovascular hypertension using nuclear medicine techniques has evolved in the past 30 years through improvements in imaging equipment, radiotracers, and, most recently, captopril intervention. Characteristic patterns of normal and abnormal renograms using typical radiotracers are demonstrated, including renal artery stenosis. Comparison with other tests, both invasive and noninvasive, are made with the aim toward identifying anatomic as well as physiologic definitions of renovascular hypertension. Pitfalls in the methodology are also described. The main advantage of captopril renography is enhancement of the sensitivity, and particularly the specificity, of the radionuclide diagnosis of renovascular hypertension. Available investigations have identified captopril renography as the likely procedure of choice in the noninvasive identification ofrenovascular hypertension.

Key words: Hypertension -- Renovascular -Captopril -- Renography.

As physicians, we would like to know etiologies and cures for diseases, especially those as prevalent and potentially serious as hypertension. The vast majority of hypertensive individuals, however, have hypertension of unknown, or essential, origin. Secondary hypertension (i.e., hypertension due to an identifiable underlying abnormality) represents no

Address offprint requests to: Eugene J. Fine, M.D., Department of Nuclear Medicine, Bronx Municipal Hospital Center, Pelham Parkway and Eastchester Road, Bronx, NY 10461, USA

more than about 10% of all hypertensives. The low prevalence of a potentially curable disease challenges all physicians to choose carefully from their hypertensive patients to avoid needless and expensive testing, in the search for a curable form of the condition. However, among the varieties of secondary hypertension, renovascular hypertension has long intrigued nephrologists, cardiologists, urologists, and vascular surgeons as the most prevalent and perhaps most curable of the secondary hypertensive diseases. Most recently, the growth of percutaneous transluminal angioplasty, and its successful application to renovascular hypertension (RVH) has revived interest in finding practical and accurate noninvasive techniques of identifying hypertensives at high risk of having R V H from among the vastly more prevalent essential hypertensives. This review attempts to define the fundamental anatomic and physiologic features of R V H with a brief description of pertinent diagnostic techniques. Nuclear medicine imaging procedures are described first in general terms, and then more specifically as they relate to the diagnosis of RVH.

RVH Goldblatt et al. [1] first described an experimental model of R V H in his classic experiments of the 1930s. These investigators were able to induce acute and chronic hypertension in clogs by tying partial ligatures about the renal arteries. When the first human being with renal artery stenosis was cured of hypertension by nephrectomy in 1938, it was felt by the eminent nephrologist, Homer Smith, that the cause of hypertension was at hand, and possibly its


cure. By 1943, however, Smith acknowledged the low frequency with which renal artery stenosis was found, and the consequent low cure rate for hypertension [2]. During this same period, renin and angiotensin were being isolated and their roles in R V H were being described. We now know that decreased renal perfusion pressure triggers renal arterial baroceptors to signal arteriolar secretion of the hormone renin [3]. Renin, in turn, acts upon angiotensinogen, an hepatic protein, to form angiotensin I, which is biologically inactive. Angiotensin I is then cleaved by angiotensin-converting enzyme, predominantly in the lung, to form angiotensin II (AII). Hypersecretion of AII is thought to be responsible for the hypertension in individuals with R V H by two mechanisms: (a) AII, directly, is a potent endogenous arterial vasoconstrictor; and (b) AII also stimulates the adrenal cortex to secrete aldosterone which promotes retention of salt by reabsorption of sodium in the kidney at the level of the distal convoluted tubule. Identification of renal artery stenosis (RAS) is usually made by contrast renal arteriography. The diagnosis of RVH, however, is not equivalent to the identification of RAS. This is clear from the observation that hypertension itself predisposes its bearers to an accelerated pace of atherosclerosis [4, 5], including potential involvement of the renal arteries. Therefore, it is difficult in a given individual to determine if RAS is the cause or the consequence of hypertension. One may say that the presence of RAS is a necessary but not sufficient condition to consider the possibility of RVH. The current state of the art permits positive identification of R V H to be made only after cure of hypertension following renovascular surgery. This impractical fact has led clinicians and investigators to search for physiologic tests to try to identify preoperatively which individuals with RAS will likely benefit from surgical intervention. Nuclear medicine renal procedures have had a relatively prominent place in the search for a suitable procedure. Radionuclide renography, as the procedure is called, has been used in a variety of forms since 1956 [6]. The ability of nuclear medicine procedures to evaluate organ function has significant consequences in the identification of RVH. R V H is, after all, a functional disorder (ischemiainduced, renin-mediated hypertension) due to an underlying anatomic lesion (RAS).

Diagnostic Tests for RVH Many tests for either RAS or R V H have been described. Some of the more noteworthy of these tests

E.J. Fine: Nuclear Medicine Evaluation of Hypertension

follow, important for either historic or practical reasons:

Invasive Split Ureteral Urine Catheterization. Renal ischemia produced by RAS is accompanied by increased sodium and water reabsorption (mediated by aldosterone, distal tubular osmotic pressures, and antidiuretic hormone). Connor et al. [7] presented data obtained from bilateral ureteral catheterization to show decreased urinary volume and sodium concentration on the affected side in comparison with the contralateral normal kidney. Further, individuals with kidneys affected in this manner demonstrated cure of hypertension following nephrectomy, in contrast to the lack of cure in hypertensive subjects whose kidneys did not demonstrate such lateralizing findings. This procedure, of course, is far too invasive to employ routinely in the evaluation of hypertensive individuals, and it has been virtually abandoned. Nonetheless, it is important historically because it provided the first attempt to identify patients with physiologic abnormalities identifiable with renal ischemia. Individual Renal Vein Renin. Another invasive procedure which is capable of identifying a fundamental physiologic feature of R V H is individual renal vein cannulation for measurement of each kidney's venous renin concentration. R V H is suggested if the ratio of the affected to the unaffected renal vein renin is greater than 1.5 [8].'This procedure, which depends upon a radioimmunoassay to determine plasma renin activity (an in vitro nuclear medicine procedure) is commonly performed at the time ofangiography so that the renal artery anatomy and physiology can be assessed together. In some institutions, however, renal vein renin determination has been abandoned, despite its attractive theoretical basis because, in practice, the specificity of the test is only about 40-50% [8]. Arteriography. This procedure, first described in the definition of renal arterial anatomy in the 1950s [9], remains the gold standard for identification of RAS, a necessary concomitant of RVH. Recent advances have included digital arteriography, whose sensitivity has reduced the amount of contrast agent required for injection. Improved, nonionic contrast materials have also reduced the risks of toxic and allergic reactions. Nonetheless, renal toxicity (acute tubular necrosis [10]) and anaphylaxis remain risks of this procedure.


E.J. Fine: Nuclear Medicine Evaluationof Hypertension Table 1. Commonlyused renal functionalradiotracers [41-44]

Radiotracer (commonly administered radioactivity) Tubular 3q.orthoiodohippurate (OIH, 300 ~Ci) J23I-OIH (300/~Ci) 99mTc-mercaptoacetyltriglycine (MAG3, 2-10 mCi)

Glomerular 99mTc-diethylenetriaminepentaacetic acid (DTPA, 5-10 mCi)

Particulate radiation

Whole Energy body of prin- radiation cipal absorbed photon dose (KeV) (rad/mCi)

Beta (electron)



13 h 6h

None None

159 140

0.010 0.004





Physical Tlh 8 days

Radionuclide Renography Nuclear medicine procedures, in general, depend upon our ability (a) to distribute a radioactive tracer to an organ of biologic interest, and (b) to detect the radioactive emissions from that organ o f interest. The detection of radioactive emissions is now performed by highly sensitive instruments (gamma cameras) capable of demonstrating scintillation images of the radioactive materials. The organ or tissue of localization of each radiotracer depends on its biochemical properties. For example, radioactive iodine (e.g., ~31Ior 123I) localizes to the thyroid gland because chemically it behaves identically to nonradioactive iodine. ~23I-orthoiodohippurate (OIH), on the other hand, uses the same radioactive emitter (radioiodine), but in the chemical form o f OIH, the compound is avidly extracted from the blood by the renal tubules. OIH is, in fact, a chemical and biological analog of paraaminohippurate (PAH) [1 1], the physiologic standard for the measurement of effective renal plasma flow due to nearly complete plasma extraction after a single passage through the kidney. Many nuclear medicine procedures are performed with technetium-99m (99mTc) as a radiolabel because of its favorable physical properties (6-h halflife, and absence of biologically undesirable particle emissions). 99mTc itself has limited biologic interest, but its physical properties, and desirable imaging characteristics, have made it the radiolabel of choice

Comments 131Ilabel may provide substantialthyroid absorbed dose, and poor imaging characteristics Expensive; not easilyavailable Expensive; but combines optimal physiologic properties of tubular agents with availabilityand optimum imaging properties of 99m-Tc label Inexpensive, with availabilityand imaging properties of 99m-Tc label, but glomerular filtraiionis not as avid an uptake mechanismas tubular secretion

if it can be incorporated into a biologically interesting chemioal compound. Several renak radiotracers have been formulated from 99roTe. Table i lists the commonly used renal functional radiotracers. Renal morphologic studies are less our concern here than renal functional studies. We will confine our remarks to 99mTc-DTPA (DTPA), 99mTc-MAG3 (MAG3), and radioiodinated OIH (using 131Ior ta3I). The radiotracers most commonly used to evaluate renal function are DTPA, MAG3, and OIH. After intravenous injection, all three are extracted from the circulation, DTPA by glomerular filtration [12], OIH by combined tubular secretion (80% of total) and glomerular filtration (20%) [13], and MAG3 by tubular secretion [14]. Protein binding influences the rate of elimination from the body, as does biological distribution in total body water, but essentially OIH and MAG3 behave similarly, while DTPA is extracted quite a bit more slowly from the circulation. Nonetheless, all share a general pattern of renal uptake, transit, and excretion. Scintiimages of normal renal studies with these tracers are displayed in Figure 1. They share the following features, regardless of tracer employed: (1) Renal uptake, in the first 3 min or so after intravenous injection, is roughly proportional to renal function (glomerular or tubular, as is appropriate to the tracer employed). (2) Renal transit from the proximal tubule (for OIH or MAG3) or from the glomerulus (for DTPA) to the renal pelvis varies according to


E.J. Fine: Nuclear Medicine Evaluation of Hypertension m






tb ,~

~ 4,


Fig. IA. Following the administration of 300 #Ci 131-I-OIH, there is prompt and symmetric uptake of radiotracer in both kidneys during the first 3 min of imaging. Normal transit of radiotracer activity is apparent by appearance of renal pelvic activity by the 3- to 6-min image. Subsequently, there is symmetric drainage and a decline in radioactivity from both kidneys. Renogram curves derived from renal ROIs on computer matrix images reflect radioactivity as a function of time within each kidney. There is rapid uptake of each renogram curve with both kidneys reaching a peak at the point that radioactivity is entering the kidney at the same rate that it is now leaving. Subsequent to this there is a rapid downslope phase reflecting net excretion of activity from the kidneys. The scintiimages and renogram curves reflect normally functioning kidneys. (Reprinted from [22] by permission of Raven Press: EJ Fine, SC Scharf, MD Blaufox, The role of nuclear medicine in evaluating the hypertensive patient. In LM Freeman, HS Weissman (eds): Nuclear Medicine A n n u a l New York: copyright © 1984 Raven Press, pp 23-79.)

nephron length and possibly other factors, but on average is from 3-6 min after intravenous injection. This is visible on the scintiimages by the normal appearance of the renal pelvis during this time interval. (3) Renal excretion follows arrival in the collecting system; in individuals with normal renal function there is minimal (MAG3 and OIH) or moderate (DTPA) radioactivity remaining in the kidney and collecting system by 30 min after injection. Computers interfaced to gamma cameras permit computer matrix image manipulation, as well as generation of histograms representing the amount o f radiotracer in the kidney as a function of time.




Fig. lB. A normal DTPA study, performed after intravenous injection of 10 mCi 99m-Tc-DTPA, reveals similar findings to the OIH study of(A). There is symmetric intense uptake within the kidneys with pelvic visualization on a 5-min image and subsequent net drainage of activity from the kidneys. Cardiac background activity is a little higher with DTPA than with OIH because of slower blood pool clearance of this glomerular-filtered agent. Renogram curves could also be obtained, although they are not displayed here. The findings on renogram curves would be similar to those for OIH, although the upslope and downslope would be more gradual.

The latter time-activity histograms, known as renograms, provide additional valuable semi-quantitative information about renal function. The normal renogram [ 15] demonstrates a rapid upslope reflecting arrival of tracer by blood flow and accumulation within the kidney by filtration and/or tubular secretion. The curve's peak usually occurs 3-6 min after injection, reflecting equalization of tracer uptake and excretion. The subsequent downslope reflects net excretion of tracer from the renal region. A normal renogram is also represented in Figure 1A. Abnormalities in renal function are seen in renal radiotracer studies, usually reflected by combined abnormalities in uptake, transit, and excretion. (The range of abnormalities in renography* is beyond the scope of this review, but is available for the interested reader elsewhere [ 16].) In RAS, the classical findings of OIH renography are reduced tracer uptake within a small kidney, with delayed time to

* Renography refers, historically, tt) the time-activity histograms of renal radioactivity, but in common modern usage refers also to the entire procedure of radiotracer renal function studies.

E.J. Fine: Nuclear Medicine Evaluation of Hypertension



1 2 "7





peak and delayed excretion, reflected both in the scintiimages and renogram curves [17] (see Fig. 2A and B). Reduced uptake is due to diminished renal blood flow, while delayed transit and excretion result from increased sodium and water reabsorption. The significance of identifying RAS includes the potential for vascular repair, now often performed by percutaneous transluminal angioplasty [ 18] (see Fig. 2C).

Renography does not always demonstrate all the expected findings in RAS, but has been demonstrated to be approximately 80-85% sensitive and spe-



Fig. IC. Normal posterior view of 99m-Tc-MAG3 sequential 3-min images is displayed after intravenous injection of 2 mCi. Similar to the OIH and DTPA studies, there is prompt active uptake of radiotracer by the kidneys symmetrically during the first 3 min after injection. Activity, in this normal study, appears in the renal pelvis by 3-6 min after injection, again reflecting normal transit. Subsequently, there is prompt net excretion of tracer from the kidneys. The normal MAG3 study combines the optimum imaging properties of a technetium-labeled tracer with the avid tubular uptake properties of OIH. Normal, symmetric renogram curves are displayed.

cific for RAS using OIH [ 19]. (Values for sensitivity and specificity for renography have not been obtained for DTPA.) While these figures are quite satisfactory for a noninvasive diagnostic procedure, and compare quite favorably to the rapid sequence intravenous urogram (IVU) and other procedures, they are not very helpful in the routine evaluation of hypertensive patients for secondary hypertension. The difficulty is the very low prevalence o f R VH in the general hypertensive population. In fact, in an unselected group of hypertensive individuals, the prevalence of RVH is probably less than 1% [20].


E.J. Fine: Nuclear Medicine Evaluation of Hypertension

Fig. 2. A A 55-year-old man with peripheral vascular disease and dill]cult-to-control hypertension was injected with 300 #Ci 131-I-OIH. There is satisfactory uptake within the right kidney with normal transit and excretion seen on both images and curves. The left kidney, however, is small and has diminished uptake with delayed transit and excretion without evidence for collecting system dilatation. The findings are compatible with RAS on the left side. The renogram is normal on the right side, but demonstrates reduced upslope with delayed peak and washout on the left side. B Angiography demonstrates atherosclerotic narrowing

of the left renal artery, confirming the renographic findings of (A). C Following angioplasty, repeat contrast arteriography reveals dilatation of the left renal artery lumen (arrow). Subsequent renograms did not reveal significant change in left renal function. Nonetheless, there was improvement in blood pressure control following the angioplastic procedure. (Reprinted from [22] by permission of Raven Press: EJ Fine, SC Scharf, MD Blaufox, The role of nuclear medicine in evaluating the hypertensive patient. In LM Freeman, HS Weissman (eds): Nuclear Medicine Annual New York: copyright © 1984 Raven Press, pp 23-79.)

T h e difficulty o f screening a general p o p u l a t i o n o f hypertensives for R V H can be illustrated in the following e x a m p l e , in which we will a s s u m e optimistic 90% sensitivity a n d specificity o f renography, simply for c o n v e n i e n c e o f calculations: A m o n g 1000 successive h y p e r t e n s i v e individuals, we would expect to find a p p r o x i m a t e l y 10 with R V H , if our prevalence estimate o f 1% is correct. I f we screen all 1000 with renography, 90% sensitivity m e a n s that we will detect nine o f 10 correctly. With a specificity o f 90% (defined as the percent o f true negatives, i.e., essential hypertensives in this example, w h o are correctly identified as negative for RAS), then 10% o f the e x a m s will be falsely positive. This results in 99 false-positive e x a m s in the r e m a i n i n g g r o u p o f 990 subjects with essential hypertension. A positive r e n o g r a m then will be present in a total o f 108 individuals, o f w h o m only nine will h a v e R V H , for a positive predictive value o f 8%. I f all patients with positive results were evaluated further

Table 2. Differential diagnosis of unilateral decrease in renal

perfusiona Renal artery stenosis Renal vein thrombosis Parenchymal renal disease Collecting system obstruction Compression of hilar vessels Perirenal abscess Perirenal hematoma Ptosis of kidney a Adapted from ref. [45], with permission. with contrast angiography, 99 w o u l d be subjected to this procedure needlessly, a n d at considerable total expense, for 108 angiograms to identify nine correctly. W h a t is needed particularly is a substantial reduction in the n u m b e r o f false-positive exams. In other words, the screening p r o c e d u r e m u s t h a v e an i m p r o v e d specificity w h e n the disease being screened is o f such low prevalence [21, 22]. While

E.J. Fine: Nuclear Medicine Evaluation of Hypertension


90% specificity is indeed an excellent measure for a noninvasive exam, it is nonetheless not good enough for a disease of 1% prevalence, such as RAS. False-positive examinations in renography result from a wide variety of conditions (see Table 2), all of which can cause reduced blood flow to the kidney, with secondarily delayed transit and excretion. It is important to note that unilateral parenchymal renal disease, such as chronic pyelonephritis and obstructive uropathy, are common enough conditions to account for the observed specificity of about 85% for renography (see Fig. 3). These conditions probably also account for similar specificities reported for the rapid sequence intravenous urogram.

Angiotensin-Converting Enzyme Inhibition (ACEI) Renography In 1983, Majd et al. [23] performed a DTPA renogram on a patient treated with captopril for control of hypertension. They observed that one kidney had virtually no uptake. After discontinuation of captopril for several days a repeat renogram demonstrated symmetric uptake by the kidneys. This patient, at angiography, was demonstrated to have RAS. The case led to many other investigations into captoprirs effects on intrarenal hemodynamics, and on its potential role as a specific marker for RAS.

Effects o f Captopril on the Kidney In order to explain the effects observed by Majd et al. [23], a number of mechanisms have been proposed [24, 25]. None of the proposed mechanisms explain all of the observed phenomena. However, a description which is consistent with much of the data [25] suggests that R V H is accompanied by increased intrarenal AII; this in turn causes primary efferent arteriolar vasoconstriction. The effect of the increase in efferent vasoconstriction is to preserve the transglomerular filtration pressure, and, consequently preserve glomerular filtration rate (GFR). (This may be considered a manifestation of the wellknown renal autoregulation phenomenon in which G F R is maintained in face of variation in renal blood flow.) However, when the manufacture of AII is blocked by the presence of captopril, efferent vasoconstriction is relieved. Consequently, transglomerular filtration pressure falls abruptly, leading to decreased GFR. This may explain the predominant findings ofcaptopril renography in R V H as follows:

DTPA. With DTPA, a glomerular-filtered agent, the postcaptopril study demonstrates a marked re-

Fig. 3. A 30-year-old woman presented with fight flank pain, and a renal calculus was demonstrated on abdominal plain film (not shown). The OIH renogram reveals normal left-sided uptake, transit, and excretion. The right kidney, however, reveals diminished uptake with delayed transit and excretion on both images and the renogram curve. The renogram curve, in fact, is indistinguishable from the kind o f curve seen in RAS (see Fig. 2A). The scintiimages are helpful in that identification of the dilated collecting system and ureter improves the specificity of the exam, allowing the diagnosis of obstruction to be made. When obstruction is accompanied by poor renal function it may be difficult to visualize the renal pelvis. Obstruction, and parenchymal disease (e.g., pyelonephritis) may, in such cases, be difficult to distinguish from the findings seen in RAS. (Reprinted from [22] by permission of Raven Press: EJ Fine, SC Scharf, MD Blaufox, The role of nuclear medicine in evaluating the hypertensive patient. In LM Freeman, HS Weissman (eds): Nuclear Medicine Annual. New York: copyright © 1984 Raven Press, pp 23-79.)

duction in uptake of DTPA on the affected side. In extreme cases, the affected side demonstrates no functional uptake at all, reflecting a fall in G F R to 0. Any renal uptake that is observed is attributable to blood pool activity without any transport across glomerular membranes, as evidenced by absence of appearance of tracer in the renal collecting system. This is consistent with Majd et al.'s [23] original observations.

Tubular Agents. Tubular agents, such as MAG3


E.J. Fine: Nuclear Medicine Evaluation of Hypertension

Fig. 4A. A 25-year-old black woman with severe hypertension, uncontrolled on multiple medications, was injected with 2 mCi 99m-Tc-MAG3. Slight asymmetry of uptake is noted in the first 5-min image, but there is satisfactory excretion seen from both kidneys by 30 rain. After captopril, however, there is still mild asymmetry of uptake, but normal transit and excretion in the left kidney with markedly delayed transit and excretion from the right renal parenchyma. No evidence for collecting system dilatation is seen on the right. Scintigraphically, the postcaptopril findings of delayed excretion are consistent with rightsided RAS. The left side is not grossly changed between the preand postcaptopril studies. ,,.,%



R .°.'"" °°°.


°°,, . . . . . . . " ° ° " ' .°°o





"10 SEC Fig. 4B. Renogram curve obtained from the precaptopril study of (A) demonstrate slight asymmetry of uptake as reflected by a lower peak uptake on the left side. There is a normal time-topeak and normal excretion bilaterally. These curves support the scintiimages obtained in 4A. They suggest the possibility of leftsided renovascular disease, but are not specific for it. and OIH, demonstrate progressive accumulation of tracer during the course of the postcaptopril study [26, 27]. T h i s h a s b e e n e x p l a i n e d a s d u e t o r e d u c e d urine formation on the affected side due to reduced GFR. Markedly slow transit of reduced urine volume through the tubules causes retention of tubular activity and would account for the findings observed w i t h O I H a n d M A G 3 (see Fig. 4). O I H , b u t n o t MAG3, demonstrates modest reduction of uptake a s well, s i n c e 2 0 % o f O I H u p t a k e is d u e to G F R [131. What remains unexplained by this mechanism is t h e a c c o m m o d a t i o n o f s o m e p a t i e n t s t o l o n g - t e r m A C E i n h i b i t o r t h e r a p y [28, 29]. I n p a r t i c u l a r , s o m e





"10 SEC Fig. 4C. The postcaptopril renograms reveal progressive accumulation on the right side, as noted in the scintiimages of(A). There is a modest delay in transit on the left side, although excretion remains normal, as the scintiimages also indicate. The findings again confirm RAS on the right side. The modest changes on the left side could represent a normal left kidney. However, one must be suspicious for bilateral disease in view of the somewhat diminished left-sided renal uptake. Bilateral RAS is often substantially more detectable on one side after captopril (see ref. [36]).

patients demonstrate false-negative studies after chronic administration of captopril despite adequately maintained blood pressure reduction. The a d e q u a c y o f c o n t i n u e d h y p o t e n s i v e effects o f c a p t o p r i l w o u l d suggest a c o n t i n u e d A C E i n h i b i t o r effect. N o n e t h e l e s s , t h e r e a p p e a r s t o b e s o m e i n t r a r e nal accommodation or compensation upon the c h r o n i c a d m i n i s t r a t i o n o f A C E i n h i b i t o r s in t h e s e p a t i e n t s . A s a r e s u l t , it is p r u d e n t t o d i s c o n t i n u e captopril or other ACE inhibitors prior to a diagnostic attempt at captopril renography.

E.J. Fine: Nuclear Medicine Evaluation of Hypertension




5. Fig. 4D. Arteriography, in fact, reveals bilateral RAS due to fibromuscular disease. It should be noted that this disease is much more c o m m o n among caucasian women than in the black population. (A-D are courtesy of Kamini Patel, M.D., Bronx Lebanon Hospital, Bronx, NY).

Other potential pitfalls, as well as other items of controversy in captopril renography include the following: 1.


The appropriate state o f hydration of the patient has not been determined. Overhydration may result in false-negative results and dehydration perhaps may result in falsepositive. Furthermore, dehydration may increase the tendency of patients toward more severe hypotensive reactions to captopril. The proper state of hydration, therefore, has not been determined. The choice of tracer is also undecided. No



consensus has yet emerged among various investigators regarding superiority o f DTPA, MAG3, or OIH [26-28, 30-36]. The selection of specific ACE inhibitors for diagnostic purposes is probably not critical. Nonetheless, some investigators have used intravenous enaloprilat [37], whereas most investigators continue to use oral captopril [23, 26-36]. Potential advantages of enaloprilat include shorter duration of the study due to its immediate onset of action. Captopril's advantage, of course, is the simplicity of oral administration. It is reasonable to be concerned about intercurrent medications, particularly antihypertensives, since many drugs in this category have well-described effects on renal blood flow, tubular function, and body fluid and electrolyte composition. However, animal experimental data, as well as limited evidence from human investigation, support the contention that most classes ofantihypertensive medication are unlikely to compromise the interpretability of captopril renography. It is probably prudent, however, to discontinue diuretics several days before captopril renography in order to reduce the likelihood of hypotension during the exam. Further, as already noted, chronic administration of ACE inhibitors may result in intrarenal adaptation and false-negative exams. Therefore, it makes sense, also, to discontinue medications in this category. Difficulties persist in detecting bilateral disease. Mann et al. [36] report that in bilateral disease it is usual that one kidney is more severely affected than the other. Further, they report that it is usual for only one kidney to manifest a classic abnormality on captopril renography, despite involvement of both kidneys with RAS (see Fig. 4). Clinically, it may not be important to detect bilateral disease until the time of angiography. This, therefore, may not be a significant problem. The utility of this study in patients with renal insufficiency is thus far not established in the literature. Poor renal function, in general, however, is more likely to result in a nondiagnostic exam. In addition, small kidneys with poor function appear unresponsive to the effects of captopril [36]. Therefore, a small kidney may in fact be afflicted with RAS and may


E.J. Fine: Nuclear Medicine Evaluation of Hypertension



be the cause o f R V H without typical diagnostic findings on a captopril renogram. Finally, the specific quantitative indices o f importance to detect captopril renography have not been agreed upon by investigators in the field. A consensus conference o f the investigators in captopril renography was held at the Cleveland Clinics in N o v e m b e r o f 1990, and is recently published in a supplement to the D e c e m b e r 1991 A m e r i c a n J o u r n a l o f H y p e r t e n s i o n . Whereas consensus was not achieved in all respects it was gratifying to find agreement in m a n y areas. T h e interested reader is referred to this volu m e [35, 38, 39]. Pelvic retention o f radiotracer, while comm o n l y bilateral, has been detected unilaterally as well in captopril renograms [26]. T h e significance o f this finding is the potential for confusion with renal parenchymal retention, a captopril renogram criterion for RAS. T h e approach to making this distinction has varied a m o n g investigators, some relying on furosemide [26] m o r e extensively than others [40]. It is fair to compromise in saying that it is often possible to distinguish pelvis from cortex by inspection. However, in difficult cases, furosemide will help, as it will e m p t y the pelvis o f radiolabeled urine, while it will not be able to clear p a r e n c h y m a l activity so effectively.

Sensitivity and Specificity of Captopril Renography Results o f studies reveal sensitivities in a wide variety o f ranges anywhere from 4 0 - 1 0 0 % for the D T P A , OIH, or M A G 3 [26-28, 30, 31, 33, 34, 36, 37]. The reported specificity o f the study is in general higher and is reported mostly in the 90-100% range. In view o f the difficulties with standard renography alluded to in the early portion o f this article, it is gratifying that there is i m p r o v e d specificity o f captopril renography for R V H .

Recommendations for Captopril Renography 1.

Discontinue diuretics (at least 5 days) and ACE inhibitors prior to the exam. Long halflife ACE inhibitors, such as lisinopril and enalopril, should be discontinued at least 1 week.

2. 3. 4.



Maintain " n o r m a l " hydration and salt balance prior to the exam. Administer 25 mg captopril 1 h prior to the renogram. Perform renogram with scintiimages and curves using D T P A , OIH, or M A G 3 , according to preference. Administer intravenous furosemide to help distinguish renal pelvic holdup from parenchymal retention, i f visual inspection o f scintiimages is inconclusive. I f the renogram is normal, the patient m a y be discharged without evidence for RAS or RVH. I f the renogram is abnormal, repeat on another day (or at least 6 h later) without captopril. Reversion to a normal renogram, or a renogram o f greater symmetry, is evidence for RAS. Further workup and evaluation is indicated, usually with arteriography.

Summary Additional investigation is needed in large prospective studies in order to establish accurate measures o f false-negative and false-positive rates for captopril renography. In the meantime, however, this useful examination has already demonstrated superior sensitivity and specificity to existing noninvasive means o f detecting RVH. In properly selected hypertensive patients, captopril renography should be the examination o f choice to screen for RAS prior to arteriography.

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Nuclear medicine evaluation of hypertension.

Noninvasive diagnosis of renovascular hypertension using nuclear medicine techniques has evolved in the past 30 years through improvements in imaging ...
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