AJH
1991;
4:678S-684S
Captopril Renography Early Observations and Diagnostic Criteria H. Yoe Oei
before administration of 25 mg Captopril, hydration to induce diuresis, the performing of 1-min sequen tial images, data acquisition with frame time not exceeding 30 sec, and the calculation of the left to right ratio. In m o s t i n s t a n c e s data f r o m C a p t o p r i l renography can be interpreted without the p r e s e n c e o f a base line study. Abnormalities o f the sequential images and the renal curves classified as grade 2 and 3 in dicate the p r e s e n c e o f renal artery stenosis. Besides, in unilateral stenosis, Captopril induced renographic abnormality can also be observed in
R
enography was introduced by Taplin in 1956. Winter, who did a thorough study of hippuran (orthoiodohippurate, OIH) renograms, di vided these curves into three phases: 1) the initial sharp rise, which is attributed to the renal blood flow; 2) a slower rise due to renal accumulation, which ends in a peak, and 3) a decline due to renal excretion of the compound, which depends on the outflow tract. During the 1960s many numeric parameters that quan tified the renogram in order to increase the sensitivity and specificity of this test for the detection of renovascu lar disease were described. The use of scintillation cam-
bilateral and segmental stenosis. Interpretation based on numeric parameters probably does not in crease the sensitivity. Alterations on mercaptoacetyltriglycine (MAG^ studies are identical to the al terations observed on orthoiodohippurate (OIH) studies. In severe stenosis, alterations in diethylenetriaminepentaacetic acid studies are different from those observed in OIH or M A G studies. Since M A G provides the best images, at present M A G is the radiopharmaceutical of choice. Am J Hypertens 1991;4:678S-684S 3
3
3
Renal artery stenosis, renography, Cap topril, mercaptoacetyltriglycine (MAG3), diethylenetriaminepentaacetic acid (DTPA), orthoiodohip purate (OIH). KEY WORDS:
eras and computer systems in the 1970s made perform ing sequential images and accurate measurement of divided renal function possible. The introduction of Tc-diethylenetriaminepentaacetic acid (DTPA) facili tated first pass studies, which can detect flow asym metry of 25 % or more. However, this had the same limitations as the hippuran study, due to the fact that asymmetry can occur in many other kidney diseases. Tc-Mercaptoacetyltriglycine (MAG ), which is ex creted mainly by tubular secretion similar to OIH, has advantages over T c - D T P A and is a suitable replace ment for [ I]OIH in routine renal studies. Due to its undesirable physical properties [ I]OIH should not be used for this test. The use of renography as a screen ing test for renovascular hypertension had almost been abandoned when C a p t o p r i l r e n o g r a p h y was i n t r o duced. Captopril challenge improves the sensitivity and specificity of renography in detecting renal artery stenosis. " 99m
99m
3
99m
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131
From the Department of Nuclear Medicine, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands. Address correspondence and reprint requests to H. Yoe Oei, MD, PhD, Department of Nuclear Medicine, University Hospital Rotter dam-Dijkzigt, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands.
© 1991 by the American Journal of Hypertension,
Inc.
1
10
0895-7061/'91/'$3.50
Downloaded from http://ajh.oxfordjournals.org/ at University of Arizona on September 7, 2015
This article describes the methods and the interpre t a t i o n of C a p t o p r i l renography. The essentials of the methods are the discontin uation of diuretics, the refraining from solid foods
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FIGURE 1. A Tc-MAG study showing grade 1 on the baseline study, turning into grade 2 during Captopril renography. Data obtained from a 33-year-old woman with a right-sided stenosis. During the baseline study (A) the curves follow a symmetrical course with a peak in the 5th min. The sequential images (B) show a smaller kidney on the right side. The start of excretion in the renal pelvis is not clearly visualized; there is indication of radioactivity in the bladder in the 4th min. In the 20th min there is no retention of activity in the kidneys. The Captopril study (Ogives a normal shape of the curve on the left; on the right the maximum height is reached much later, followed by a slight fall. The sequential images (D) show the left ureter in the 3rd min, whereas the right ureter is not distinctly visible until the 20th min. 99m
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all diuretics 3 days before the examination. Patients on low maintenance doses of angiotensin converting en zyme inhibitors receive a single dose of 25 mg Captopril, whereas other patients take their own prescribed dose at the appropriate time before the renography. Hydration is mandatory, because a low urine flow will cause a slow decrease of the excretion phase in the contralateral kid ney making interpretation difficult. For this purpose we ask the patients to drink 0.5 L of water commencing 1 h before the test.
Patient's Preparation In our initial study protocol, both baseline renography and Captopril renography are performed in all patients. However, as a screening pro cedure it is more efficient to perform the Captopril renog raphy first, and only proceed with an additional study without Captopril in equivocal studies. For this test, we give 25 mg Captopril 1 h before the renography. To ensure better absorption, we ask the patients not to use Acquisition Protocol We perform renography in the solid food during the 4 h preceding the test and to chew supine position. In this position the difference between the Captopril tablet. We recommend that investigators the distances from the skin to both kidneys is small, take the blood pressure recordings every 15 to 30 min, therefore, for the calculation of the left to right ratio the because a significant fall in blood pressure can be ob depth correction can be omitted. Moreover, in the su served after a single dose of Captopril, particularly in pine position vasovagal reaction and movement arti patients using diuretics. Consequently, we discontinue facts are not observed. 11,12
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FIGURE 2. A MAG study showing grade 1 on baseline study turning into grade 3 after Captopril Data obtained from a 38-year-old man with a right-sided stenosis. The baseline renogram (A) shows an almost equal time to peak for both kidneys. As demonstrated by the sequential images (B) the slower excretion for the right kidney is due to pooling in the renal pelvis. The start of excretion is visualized on the 4th min image. On the study after Captopril administration performed 2 h later the right kidney shows an accumulation curve (C) and the images demonstrate parenchymal retention in the right kidney (Ό). 3
In the literature the duration of the study varies be tween 20 and 30 min. We feel, however, that a study length of 15 min is sufficient. During the study, we make sequential analog images of 1 min, which are essential for the interpretation of the study. Without performing the flow study, digital data acquisition of the whole study can be accomplished with the same frame time. In the literature the frame time used for this purpose varies between 10 and 30 sec. If deconvolution is applied, data should be collected in 10-sec frames. 11,12
in the literature, including time to peak, time to half peak, discriminant ratio, relative excretion delay, and residual cortical activity. ' ' 3
12,15
16
INTERPRETATION Based on our growing experience in recognizing renographic abnormalities due to unilateral stenosis and material from the literature on this subject, we would like to suggest the following guidelines and observa tions. " ' In general the renographic alterations in unilateral stenosis induced by Captopril on M A G studies are identical to the alterations observed on OIH studies. In severe stenosis the alterations in DTPA studies are dif ferent from those observed in OIH or M A G studies. The renographic abnormality in unilateral renal ar tery stenosis can almost always be appreciated by in spection of the sequential images and the renal curves. Interpretation based on numeric parameters probably does not increase the sensitivity of the technique. 10
12
17
25
3
Numeric Parameters The most important parameter derived from the secretion phase is the split renal func tion or left to right ratio. The normal range for each kidney varies from 4 5 % to 5 5 % . In our previous publi cation on OIH studies we called it the relative hippuran uptake, which is generally lower in the kidney behind the stenosis than in the contralateral o n e . Many pa rameters from the excretion phase have been described 13,14
3
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OIH and M A G Studies in Unilateral Stenosis Based on the excretion pattern of OIH, three types of abnor mality were observed in patients with renovascular hy pertension due to unilateral stenosis. 3
13
Grade 1 The sequential images generally show a smaller kidney with less uptake than in the contralateral kidney on the affected side. The excretion is not im peded; both kidneys show an equal time to peak.
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Grade 3 In this group the affected kidney is always smaller than the contralateral one and does not show any excretion during the study. The sequential images visualize a parenchymal retention. The renogram shows an accumulation curve. If both studies—baseline and Captopril renography —are performed, the following alterations should be regarded as indications for the presence of unilateral stenosis: 1) baseline study of grade 1, which after Capto pril challenge changes into grade 2 (Figure 1); 2) baseline study of grade 1 or grade 2, which changes into grade 3 (Figure 2); 3) baseline study of grade 3, in which case Captopril administration will not cause any change. If only Captopril renography is performed, the test should be regarded as positive in cases showing grade 2 or grade 3. We are convinced that the sequential images
Uil L
I L IM L M I II M ::! RH I IM I N 11 M L M L I I I Uli L II M L I L I RI I I I I LL LUI L I I II LLLLLLL L L L I L M
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Ρ
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I
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D Π
I
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LLL LL IL L LL L L ILLLLl LUiLl L LU L L L LLL I L L LLL L-
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FIGURE 3. A DTPA study showing grade 1 abnormality on the baseline study turning into grade 2 after Captopril. Data obtained from a 13-year-old girl with a right-sided stenosis. The baseline renogram (A) shows on the right less uptake than on the left; split renal function of the right kidney is 42%. Time to peak of the right kidney is 4 min longer than of the left one. The sequential images (B) show a slightly smaller right kidney. The excretion for both sides starts in the 5th min. At the 18th min there is a pooling of radioactivity in the right renal pelvis. The Captopril renogram (C) indicates on the right side an accumulation curve. Split renal function of the right kidney is 38%, a decrease of only 4%. The sequential images (D) show a parenchymal retention on the right side.
Downloaded from http://ajh.oxfordjournals.org/ at University of Arizona on September 7, 2015
Grade 2 As in grade 1, the affected kidney is almost always smaller and shows less uptake than the contralat eral kidney. The start of excretion of the radionuclide in the renal pelvis of the affected kidney is delayed. The curve of the affected side shows an excretion phase with a longer time to peak than that of the contralateral kidney.
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FIGURE 4. A DTPA study showing grade 1 on the baseline turning into grade 3 after Captopril. Data obtained from a 56-year-old man with a left-sided stenosis. The baseline renogram (A) indicates a lower uptake in the left kidney and a longer time to peak than on the right side. Split renal function of the left kidney is 28%. The sequential images (B) show a smaller left kidney. The start of excretion in the right renal pelvis is shown in the 5th min; no determination is possible on the left side. At the 18th min there is a slight retention in both kidneys. The Captopril renogram (C) shows a curve with a flattened course for the affected kidney. Split renal function of the left kidney is 15%, a fall of 13% compared to the baseline study. On the sequential images (D) the left kidney is barely visible.
play an important role in differentiating between true positive and false positive tests. As shown in the figures, the images obtained using M A G are superior and facili tate the appreciation of the abnormality encountered after Captopril challenge. 3
DTPA Studies in Unilateral Stenosis The abnormali ties due to unilateral stenosis observed in DTPA studies can also be divided into three categories. Grade 1 and grade 2 are identical to the first two grades of the O I H / M A G studies. Also classified under grade 2 are those cases in DTPA studies with both an accumulation curve and parenchymal retention on the sequential images (Figure 3). In the grade 3 pattern the sequential images show a faint visualization of the affected kidney. This kidney is most clearly visualized on the first two images, after which the activity tends to decrease. The curve shows an early peak due to the first transit, which ap 3
pears earlier than the real peak of the contralateral kid ney. After the peak the curve of the affected kidney shows a decrease resembling the blood background curve (Figure 4). If only a study after Captopril challenge is available, the test should be interpreted as positive if a grade 2 or grade 3 pattern.is encountered. DISCUSSION Without Captopril challenge, about 5 0 % of the patients with hemodynamically significant unilateral stenosis will show a grade 1 pattern, which is not diagnostic for unilateral stenosis since it is also observed in patients with unilateral loss of renal mass due to other renal diseases, and in patients with a congenital hypoplastic kidney. Renal curves showing a unilateral delay of time to
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possible in patients with serum creatinine around 300 /imol/L. We feel that this limit will be lower if DTPA is applied. In our study in which T c - D T P A and [ I]OIH were administered consecutively, recognizing alteration on the DTPA renogram was as easy as on the OIH reno gram in those patients whose split function of the af fected kidney was greater than 25 % of the total func tion. However, in kidneys with more severe renal insufficiency, the changes induced by Captopril on the OIH curves were easier to detect than on the DTPA curves. This observation is confirmed by Sfakianakis et al. In studies using DTPA a decrease of the split renal function of the affected kidney of more than 5 % was regarded as the most important sign of renal artery ste nosis. However, a decrease of the split renal function will not be observed in cases showing a grade 3 pattern on the baseline study. Also in patients showing a grade 2 pattern after Captopril challenge, the decrease of the split renal function compared to the baseline study is less obvious, as in the case shown in Figure 3. In summary it can be concluded that grade 2 and 3 abnormalities indicate the presence of renal artery steno sis. Captopril induced renographic abnormality can al most always be appreciated by inspection of the se quential images and the renal curves. Besides, in unilateral stenosis Captopril induced alterations can also be observed in bilateral and segmental stenosis. Inter pretation based on numeric parameters probably does not increase the sensitivity. Since M A G provides the best images, at present M A G is the radiopharmaceuti cal of choice. 99m
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11,12
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REFERENCES 1. Blaufox MD: The role of nuclear medicine. A historical perspective, in Blaufox MD (ed): Evaluation of Renal Function and Disease With Radionuclides: The Upper Urinary Tract. Basel, Karger, 1989, pp 2 - 9 . 2. Blaufox MD, Freeman LM: Renewed role of nuclear med icine in renovascular hypertension. Urol Radiol 1988;10:35-38.
3
3.
TABLE 1. SENSITIVITY AND SPECIFICITY OF CAPTOPRIL RENOGRAPHY Author 17
Cuocolo Dondi Fommei Maher Pedersen 18
20
21
23
RVH
EH
Sensitivity
Specificity
5 50 15 15 14
6 55 24 29 10
100 92 87 85 93
100 97 100 72 100
RVH = renovascular
hypertension,
EH = essential
hypertension.
Gault MH, Sidhu JS, Fuks A: The 131-I-hippurate reno gram as a quantitative test of function in renal parenchy mal disease. Nephron 1973;11:354-364.
4. Jafri RA, Britton KE, Nimmon CC, et al: Technetium99m MAG , a comparison with iodine-123 and iodine131 orthoiodohippurate, in patients with renal disorders. J Nucl Med 1988;29:147-158. 3
5. Nally JV, Clarke HS, Windham JP, et al: Technetium99m DTPA renal flow studies in Goldblatt hypertension. J Nucl Med 1985;26:917-924. 6. Oei HY, Geyskes GG, Dorhout Mees EJ, Puylaert CBAJ: Captopril induced renographic alteration in unilateral renal artery stenosis (abst). J Nucl Med 1984;25:P36. 7. Russell CD, Thorstad B, Yester MV, et al: Comparison of
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peak as seen in grade 2 or even an accumulation curve as in grade 3 can be observed in patients with a volumi nous or dilated renal pelvis in particular if the urine flow during the study is low. In these cases the start of excre tion of the radionuclide in both renal pelves visualized on the images will take place simultaneously. Differen tiation from a true positive case can sometimes hardly be made, leading to a false positive interpretation. Grade 3 pattern should be differentiated from abnormalities due to urinary tract obstruction, in which the affected kid ney is generally larger than the contralateral one and shows a dilated pyelocaliceal system visualized as pho ton-deficient areas. Clinical and experimental studies have shown the potential use of C a p t o p r i l renography to detect renovascular hypertension due to bilateral stenosis, which occurs in approximately 3 0 % of the pa tients. 18,20,23,24,26,27 According to our observations, C a p topril challenge leads in most instances to a delayed OIH excretion from one kidney. Sometimes a simultaneous disturbance of excretion from both kidneys can be ob served. However, this last phenomenon cannot be dif ferentiated from abnormalities seen in patients having a severe drop of the blood pressure. The prevalence of segmental stenosis is approxi mately 5 % of the patients with renal artery stenosis. Segmental stenosis has also been recognized by means of Captopril renography. ' Appreciation will be more difficult if the area vascularized by the diseased arterial branch is smaller. Table 1 summarizes the results of clinical studies on C a p t o p r i l renography. Although in these articles the prevalence of renal artery stenosis in the patients stud ied is higher than in an unselected population, the sensi tivity and specificity obtained warrant a further study on the suitability of this technique as a screening test. The lowest sensitivity and specificity were observed in the study of Maher et al, in which all patients, in cluding patients with renal insufficiency, were included. This result may be partly due to the use of DTPA, be cause in patients with renal insufficiency appreciation of renographic changes in DTPA studies can be difficult. Using OIH or M A G recognition of unilateral stenosis is
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technetium-99m MAG with iodine-131 hippuran by a simultaneous dual channel technique. J Nucl Med 1988;29:1189-1193. Taylor A, Jr., Eshima D, Fritzberg AR, Christian PE: Com parison of iodine-131 OIH and technetium-99m MAG renal imaging in volunteers. J Nucl Med 1986;27:795803. Taylor A, Jr., Eshima D, Christian PE, et al: Technetium99m MAG kit formulation: preliminary results in nor mal volunteers and patients with renal failure. J Nucl Med 1988;29:616-622. 3
8.
3
9.
Dondi M, Franchi R, Levorato M, et al: Evaluation of hypertensive patients by means of Captopril enhanced renal scintigraphy with technetium-99m DTPA. J Nucl Med 1989;30:615-621.
19.
Fine EJ, Sarkar S: Differential diagnosis and manage ment of renovascular hypertension through nuclear med icine techniques. Semin Nucl Med 1989;19:101-115.
20.
Fommei E, Ghione S, Palla L, et al: Renal scintigraphic Captopril test in the diagnosis of renovascular hyperten sion. Hypertension 1987;10:212-220.
21.
Maher ER, Othman S, Frankel AH, et al: captopril-enhanced T c DTPA scintigraphy in the detection of renal-artery stenosis. Nephrol Dial Transplant 1988;3:608-611. 99m
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14.
22.
Nally JV, Jr., Clarke HS, Gupta BK, et al: Captopril ren ography in two kidney and one kidney Goldblatt hyper tension in dogs. J Nucl Med 1987;28:1171-1179.
23.
Pedersen EB, Jensen FT, Eiskjaer H, et al: Differentiation between renovascular and essential hypertension by means of changes in single kidney Tc-DTPA clear ance induced by angiotensin converting enzyme inhibi tion. Am J Hypertens 1989;2:323-334. 99m
24.
Geyskes GG, Oei HY, Faber JAJ: Renography: prediction of blood pressure after dilatation of renal artery stenosis. Nephron 1986;44(suppl l):54-59.
Sfakianakis GN, Bourgoignie JJ, Jaffe D, et al: Single dose Captopril scintigraphy in the diagnosis of renovascu lar hypertension. J Nucl Med 1987;28:1383-1392.
25.
Geyskes GG, Oei HY, Klinge J, et al: Renovascular hy pertension. The small kidney updated. Q J Med 1988;251:203-217.
26.
Wenting GJ, Tan-Tjiong HL, Derkx FHM, et al: Split renal functions after Captopril in unilateral renal artery stenosis. Br Med J 1984; 288:886-890. Nally JV, Jr., Bedoya LA, Park CH, et al: Captopril-stimulated renography versus renal vein renins in two-kid ney, two-clip hypertension, in Blaufox MD, Hollenberg NK, Raynayd C (eds): Radionuclides in Nephro-Urology, Contributions to Nephrology, Vol. 79. Basel, Karger, 1990, pp 176-180.
15.
Farmelant MH, Burrows BA: The renogram: physiologic basis and current clinical use. Semin Nucl Med 1974;4:61-72. 16. Sfakianakis GN, Sfakianaki E, Bourgoignie J: Renal scin tigraphy following angiotensin converting enzyme inhi bition in the diagnosis of renovascular hypertension (Captopril scintigraphy), in Freeman LM (ed): Nuclear Medicine Annual. New York, Raven Press, 1988, pp 125-170. 17. Cuocolo A, Esposito S, Volpe M, Celentano L, et al: Renal artery stenosis detection by combined Gates' technique and Captopril test in hypertensive patients. J Nucl Med 1989;30:51-56.
27.
Itoh K, Shinohara M, Togashi M, Koyanagi T: Captopril renal scintigraphy in a patient with bilateral renal artery stenosis. J Nucl Med 1989;30:2042-2045.
28.
Fommei E, Bellina R, Berteiii P, et al: Interactive func tional imaging of renal scintigraphy after Captopril in the detection of global and segmental hypoperfusion, in Bis chof-Delaloye A, Blaufox MD (eds): Radianuclides in Nephrology, Contributions to Nephrology, Vol. 56. Basel, Karger, 1987, pp 111-116.
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3
Thorstad BL, Russell CD, Dubovsky EV, Keller FS, et al: Abnormal Captopril renogram with a technetium-99mlabeled hippuran analog. J Nucl Med 1988;29:17301737. 11. Geyskes GG, Oei HY, Puylaert CBAJ, Dorhout Mees EJ: Renovascular hypertension identified by captopril-induced changes in the renogram. Hypertension 1987;9:451-458. 12. Oei HY, Geyskes GG, Dorhout Mees EJ, Puylaert CBAJ: The significance of Captopril renography in renovascular hypertension, in Bischof-Delaloye A, Blaufox MD (eds): Radionuclides in Nephrology, Contributions to Nephrol ogy, Vol. 56. Basel, Karger, 1987, pp 95-103.
1991-VOL
1991;
4:678S-684S
Captopril Renography Early Observations and Diagnostic Criteria H. Yoe Oei
before administration of 25 mg Captopril, hydration to induce diuresis, the performing of 1-min sequen tial images, data acquisition with frame time not exceeding 30 sec, and the calculation of the left to right ratio. In m o s t i n s t a n c e s data f r o m C a p t o p r i l renography can be interpreted without the p r e s e n c e o f a base line study. Abnormalities o f the sequential images and the renal curves classified as grade 2 and 3 in dicate the p r e s e n c e o f renal artery stenosis. Besides, in unilateral stenosis, Captopril induced renographic abnormality can also be observed in
R
enography was introduced by Taplin in 1956. Winter, who did a thorough study of hippuran (orthoiodohippurate, OIH) renograms, di vided these curves into three phases: 1) the initial sharp rise, which is attributed to the renal blood flow; 2) a slower rise due to renal accumulation, which ends in a peak, and 3) a decline due to renal excretion of the compound, which depends on the outflow tract. During the 1960s many numeric parameters that quan tified the renogram in order to increase the sensitivity and specificity of this test for the detection of renovascu lar disease were described. The use of scintillation cam-
bilateral and segmental stenosis. Interpretation based on numeric parameters probably does not in crease the sensitivity. Alterations on mercaptoacetyltriglycine (MAG^ studies are identical to the al terations observed on orthoiodohippurate (OIH) studies. In severe stenosis, alterations in diethylenetriaminepentaacetic acid studies are different from those observed in OIH or M A G studies. Since M A G provides the best images, at present M A G is the radiopharmaceutical of choice. Am J Hypertens 1991;4:678S-684S 3
3
3
Renal artery stenosis, renography, Cap topril, mercaptoacetyltriglycine (MAG3), diethylenetriaminepentaacetic acid (DTPA), orthoiodohip purate (OIH). KEY WORDS:
eras and computer systems in the 1970s made perform ing sequential images and accurate measurement of divided renal function possible. The introduction of Tc-diethylenetriaminepentaacetic acid (DTPA) facili tated first pass studies, which can detect flow asym metry of 25 % or more. However, this had the same limitations as the hippuran study, due to the fact that asymmetry can occur in many other kidney diseases. Tc-Mercaptoacetyltriglycine (MAG ), which is ex creted mainly by tubular secretion similar to OIH, has advantages over T c - D T P A and is a suitable replace ment for [ I]OIH in routine renal studies. Due to its undesirable physical properties [ I]OIH should not be used for this test. The use of renography as a screen ing test for renovascular hypertension had almost been abandoned when C a p t o p r i l r e n o g r a p h y was i n t r o duced. Captopril challenge improves the sensitivity and specificity of renography in detecting renal artery stenosis. " 99m
99m
3
99m
123
131
From the Department of Nuclear Medicine, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands. Address correspondence and reprint requests to H. Yoe Oei, MD, PhD, Department of Nuclear Medicine, University Hospital Rotter dam-Dijkzigt, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands.
© 1991 by the American Journal of Hypertension,
Inc.
1
10
0895-7061/'91/'$3.50
Downloaded from http://ajh.oxfordjournals.org/ at University of Arizona on September 7, 2015
This article describes the methods and the interpre t a t i o n of C a p t o p r i l renography. The essentials of the methods are the discontin uation of diuretics, the refraining from solid foods
AJH-DECEMBER
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1991-VOL.
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15
4, NO. 12, PART 2
EARLY OBSERVATIONS AND DIAGNOSTIC CRITERIA
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C
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FIGURE 1. A Tc-MAG study showing grade 1 on the baseline study, turning into grade 2 during Captopril renography. Data obtained from a 33-year-old woman with a right-sided stenosis. During the baseline study (A) the curves follow a symmetrical course with a peak in the 5th min. The sequential images (B) show a smaller kidney on the right side. The start of excretion in the renal pelvis is not clearly visualized; there is indication of radioactivity in the bladder in the 4th min. In the 20th min there is no retention of activity in the kidneys. The Captopril study (Ogives a normal shape of the curve on the left; on the right the maximum height is reached much later, followed by a slight fall. The sequential images (D) show the left ureter in the 3rd min, whereas the right ureter is not distinctly visible until the 20th min. 99m
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all diuretics 3 days before the examination. Patients on low maintenance doses of angiotensin converting en zyme inhibitors receive a single dose of 25 mg Captopril, whereas other patients take their own prescribed dose at the appropriate time before the renography. Hydration is mandatory, because a low urine flow will cause a slow decrease of the excretion phase in the contralateral kid ney making interpretation difficult. For this purpose we ask the patients to drink 0.5 L of water commencing 1 h before the test.
Patient's Preparation In our initial study protocol, both baseline renography and Captopril renography are performed in all patients. However, as a screening pro cedure it is more efficient to perform the Captopril renog raphy first, and only proceed with an additional study without Captopril in equivocal studies. For this test, we give 25 mg Captopril 1 h before the renography. To ensure better absorption, we ask the patients not to use Acquisition Protocol We perform renography in the solid food during the 4 h preceding the test and to chew supine position. In this position the difference between the Captopril tablet. We recommend that investigators the distances from the skin to both kidneys is small, take the blood pressure recordings every 15 to 30 min, therefore, for the calculation of the left to right ratio the because a significant fall in blood pressure can be ob depth correction can be omitted. Moreover, in the su served after a single dose of Captopril, particularly in pine position vasovagal reaction and movement arti patients using diuretics. Consequently, we discontinue facts are not observed. 11,12
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FIGURE 2. A MAG study showing grade 1 on baseline study turning into grade 3 after Captopril Data obtained from a 38-year-old man with a right-sided stenosis. The baseline renogram (A) shows an almost equal time to peak for both kidneys. As demonstrated by the sequential images (B) the slower excretion for the right kidney is due to pooling in the renal pelvis. The start of excretion is visualized on the 4th min image. On the study after Captopril administration performed 2 h later the right kidney shows an accumulation curve (C) and the images demonstrate parenchymal retention in the right kidney (Ό). 3
In the literature the duration of the study varies be tween 20 and 30 min. We feel, however, that a study length of 15 min is sufficient. During the study, we make sequential analog images of 1 min, which are essential for the interpretation of the study. Without performing the flow study, digital data acquisition of the whole study can be accomplished with the same frame time. In the literature the frame time used for this purpose varies between 10 and 30 sec. If deconvolution is applied, data should be collected in 10-sec frames. 11,12
in the literature, including time to peak, time to half peak, discriminant ratio, relative excretion delay, and residual cortical activity. ' ' 3
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INTERPRETATION Based on our growing experience in recognizing renographic abnormalities due to unilateral stenosis and material from the literature on this subject, we would like to suggest the following guidelines and observa tions. " ' In general the renographic alterations in unilateral stenosis induced by Captopril on M A G studies are identical to the alterations observed on OIH studies. In severe stenosis the alterations in DTPA studies are dif ferent from those observed in OIH or M A G studies. The renographic abnormality in unilateral renal ar tery stenosis can almost always be appreciated by in spection of the sequential images and the renal curves. Interpretation based on numeric parameters probably does not increase the sensitivity of the technique. 10
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Numeric Parameters The most important parameter derived from the secretion phase is the split renal func tion or left to right ratio. The normal range for each kidney varies from 4 5 % to 5 5 % . In our previous publi cation on OIH studies we called it the relative hippuran uptake, which is generally lower in the kidney behind the stenosis than in the contralateral o n e . Many pa rameters from the excretion phase have been described 13,14
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OIH and M A G Studies in Unilateral Stenosis Based on the excretion pattern of OIH, three types of abnor mality were observed in patients with renovascular hy pertension due to unilateral stenosis. 3
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Grade 1 The sequential images generally show a smaller kidney with less uptake than in the contralateral kidney on the affected side. The excretion is not im peded; both kidneys show an equal time to peak.
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Grade 3 In this group the affected kidney is always smaller than the contralateral one and does not show any excretion during the study. The sequential images visualize a parenchymal retention. The renogram shows an accumulation curve. If both studies—baseline and Captopril renography —are performed, the following alterations should be regarded as indications for the presence of unilateral stenosis: 1) baseline study of grade 1, which after Capto pril challenge changes into grade 2 (Figure 1); 2) baseline study of grade 1 or grade 2, which changes into grade 3 (Figure 2); 3) baseline study of grade 3, in which case Captopril administration will not cause any change. If only Captopril renography is performed, the test should be regarded as positive in cases showing grade 2 or grade 3. We are convinced that the sequential images
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FIGURE 3. A DTPA study showing grade 1 abnormality on the baseline study turning into grade 2 after Captopril. Data obtained from a 13-year-old girl with a right-sided stenosis. The baseline renogram (A) shows on the right less uptake than on the left; split renal function of the right kidney is 42%. Time to peak of the right kidney is 4 min longer than of the left one. The sequential images (B) show a slightly smaller right kidney. The excretion for both sides starts in the 5th min. At the 18th min there is a pooling of radioactivity in the right renal pelvis. The Captopril renogram (C) indicates on the right side an accumulation curve. Split renal function of the right kidney is 38%, a decrease of only 4%. The sequential images (D) show a parenchymal retention on the right side.
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Grade 2 As in grade 1, the affected kidney is almost always smaller and shows less uptake than the contralat eral kidney. The start of excretion of the radionuclide in the renal pelvis of the affected kidney is delayed. The curve of the affected side shows an excretion phase with a longer time to peak than that of the contralateral kidney.
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FIGURE 4. A DTPA study showing grade 1 on the baseline turning into grade 3 after Captopril. Data obtained from a 56-year-old man with a left-sided stenosis. The baseline renogram (A) indicates a lower uptake in the left kidney and a longer time to peak than on the right side. Split renal function of the left kidney is 28%. The sequential images (B) show a smaller left kidney. The start of excretion in the right renal pelvis is shown in the 5th min; no determination is possible on the left side. At the 18th min there is a slight retention in both kidneys. The Captopril renogram (C) shows a curve with a flattened course for the affected kidney. Split renal function of the left kidney is 15%, a fall of 13% compared to the baseline study. On the sequential images (D) the left kidney is barely visible.
play an important role in differentiating between true positive and false positive tests. As shown in the figures, the images obtained using M A G are superior and facili tate the appreciation of the abnormality encountered after Captopril challenge. 3
DTPA Studies in Unilateral Stenosis The abnormali ties due to unilateral stenosis observed in DTPA studies can also be divided into three categories. Grade 1 and grade 2 are identical to the first two grades of the O I H / M A G studies. Also classified under grade 2 are those cases in DTPA studies with both an accumulation curve and parenchymal retention on the sequential images (Figure 3). In the grade 3 pattern the sequential images show a faint visualization of the affected kidney. This kidney is most clearly visualized on the first two images, after which the activity tends to decrease. The curve shows an early peak due to the first transit, which ap 3
pears earlier than the real peak of the contralateral kid ney. After the peak the curve of the affected kidney shows a decrease resembling the blood background curve (Figure 4). If only a study after Captopril challenge is available, the test should be interpreted as positive if a grade 2 or grade 3 pattern.is encountered. DISCUSSION Without Captopril challenge, about 5 0 % of the patients with hemodynamically significant unilateral stenosis will show a grade 1 pattern, which is not diagnostic for unilateral stenosis since it is also observed in patients with unilateral loss of renal mass due to other renal diseases, and in patients with a congenital hypoplastic kidney. Renal curves showing a unilateral delay of time to
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possible in patients with serum creatinine around 300 /imol/L. We feel that this limit will be lower if DTPA is applied. In our study in which T c - D T P A and [ I]OIH were administered consecutively, recognizing alteration on the DTPA renogram was as easy as on the OIH reno gram in those patients whose split function of the af fected kidney was greater than 25 % of the total func tion. However, in kidneys with more severe renal insufficiency, the changes induced by Captopril on the OIH curves were easier to detect than on the DTPA curves. This observation is confirmed by Sfakianakis et al. In studies using DTPA a decrease of the split renal function of the affected kidney of more than 5 % was regarded as the most important sign of renal artery ste nosis. However, a decrease of the split renal function will not be observed in cases showing a grade 3 pattern on the baseline study. Also in patients showing a grade 2 pattern after Captopril challenge, the decrease of the split renal function compared to the baseline study is less obvious, as in the case shown in Figure 3. In summary it can be concluded that grade 2 and 3 abnormalities indicate the presence of renal artery steno sis. Captopril induced renographic abnormality can al most always be appreciated by inspection of the se quential images and the renal curves. Besides, in unilateral stenosis Captopril induced alterations can also be observed in bilateral and segmental stenosis. Inter pretation based on numeric parameters probably does not increase the sensitivity. Since M A G provides the best images, at present M A G is the radiopharmaceuti cal of choice. 99m
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3
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REFERENCES 1. Blaufox MD: The role of nuclear medicine. A historical perspective, in Blaufox MD (ed): Evaluation of Renal Function and Disease With Radionuclides: The Upper Urinary Tract. Basel, Karger, 1989, pp 2 - 9 . 2. Blaufox MD, Freeman LM: Renewed role of nuclear med icine in renovascular hypertension. Urol Radiol 1988;10:35-38.
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TABLE 1. SENSITIVITY AND SPECIFICITY OF CAPTOPRIL RENOGRAPHY Author 17
Cuocolo Dondi Fommei Maher Pedersen 18
20
21
23
RVH
EH
Sensitivity
Specificity
5 50 15 15 14
6 55 24 29 10
100 92 87 85 93
100 97 100 72 100
RVH = renovascular
hypertension,
EH = essential
hypertension.
Gault MH, Sidhu JS, Fuks A: The 131-I-hippurate reno gram as a quantitative test of function in renal parenchy mal disease. Nephron 1973;11:354-364.
4. Jafri RA, Britton KE, Nimmon CC, et al: Technetium99m MAG , a comparison with iodine-123 and iodine131 orthoiodohippurate, in patients with renal disorders. J Nucl Med 1988;29:147-158. 3
5. Nally JV, Clarke HS, Windham JP, et al: Technetium99m DTPA renal flow studies in Goldblatt hypertension. J Nucl Med 1985;26:917-924. 6. Oei HY, Geyskes GG, Dorhout Mees EJ, Puylaert CBAJ: Captopril induced renographic alteration in unilateral renal artery stenosis (abst). J Nucl Med 1984;25:P36. 7. Russell CD, Thorstad B, Yester MV, et al: Comparison of
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peak as seen in grade 2 or even an accumulation curve as in grade 3 can be observed in patients with a volumi nous or dilated renal pelvis in particular if the urine flow during the study is low. In these cases the start of excre tion of the radionuclide in both renal pelves visualized on the images will take place simultaneously. Differen tiation from a true positive case can sometimes hardly be made, leading to a false positive interpretation. Grade 3 pattern should be differentiated from abnormalities due to urinary tract obstruction, in which the affected kid ney is generally larger than the contralateral one and shows a dilated pyelocaliceal system visualized as pho ton-deficient areas. Clinical and experimental studies have shown the potential use of C a p t o p r i l renography to detect renovascular hypertension due to bilateral stenosis, which occurs in approximately 3 0 % of the pa tients. 18,20,23,24,26,27 According to our observations, C a p topril challenge leads in most instances to a delayed OIH excretion from one kidney. Sometimes a simultaneous disturbance of excretion from both kidneys can be ob served. However, this last phenomenon cannot be dif ferentiated from abnormalities seen in patients having a severe drop of the blood pressure. The prevalence of segmental stenosis is approxi mately 5 % of the patients with renal artery stenosis. Segmental stenosis has also been recognized by means of Captopril renography. ' Appreciation will be more difficult if the area vascularized by the diseased arterial branch is smaller. Table 1 summarizes the results of clinical studies on C a p t o p r i l renography. Although in these articles the prevalence of renal artery stenosis in the patients stud ied is higher than in an unselected population, the sensi tivity and specificity obtained warrant a further study on the suitability of this technique as a screening test. The lowest sensitivity and specificity were observed in the study of Maher et al, in which all patients, in cluding patients with renal insufficiency, were included. This result may be partly due to the use of DTPA, be cause in patients with renal insufficiency appreciation of renographic changes in DTPA studies can be difficult. Using OIH or M A G recognition of unilateral stenosis is
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technetium-99m MAG with iodine-131 hippuran by a simultaneous dual channel technique. J Nucl Med 1988;29:1189-1193. Taylor A, Jr., Eshima D, Fritzberg AR, Christian PE: Com parison of iodine-131 OIH and technetium-99m MAG renal imaging in volunteers. J Nucl Med 1986;27:795803. Taylor A, Jr., Eshima D, Christian PE, et al: Technetium99m MAG kit formulation: preliminary results in nor mal volunteers and patients with renal failure. J Nucl Med 1988;29:616-622. 3
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Dondi M, Franchi R, Levorato M, et al: Evaluation of hypertensive patients by means of Captopril enhanced renal scintigraphy with technetium-99m DTPA. J Nucl Med 1989;30:615-621.
19.
Fine EJ, Sarkar S: Differential diagnosis and manage ment of renovascular hypertension through nuclear med icine techniques. Semin Nucl Med 1989;19:101-115.
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Fommei E, Ghione S, Palla L, et al: Renal scintigraphic Captopril test in the diagnosis of renovascular hyperten sion. Hypertension 1987;10:212-220.
21.
Maher ER, Othman S, Frankel AH, et al: captopril-enhanced T c DTPA scintigraphy in the detection of renal-artery stenosis. Nephrol Dial Transplant 1988;3:608-611. 99m
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Nally JV, Jr., Clarke HS, Gupta BK, et al: Captopril ren ography in two kidney and one kidney Goldblatt hyper tension in dogs. J Nucl Med 1987;28:1171-1179.
23.
Pedersen EB, Jensen FT, Eiskjaer H, et al: Differentiation between renovascular and essential hypertension by means of changes in single kidney Tc-DTPA clear ance induced by angiotensin converting enzyme inhibi tion. Am J Hypertens 1989;2:323-334. 99m
24.
Geyskes GG, Oei HY, Faber JAJ: Renography: prediction of blood pressure after dilatation of renal artery stenosis. Nephron 1986;44(suppl l):54-59.
Sfakianakis GN, Bourgoignie JJ, Jaffe D, et al: Single dose Captopril scintigraphy in the diagnosis of renovascu lar hypertension. J Nucl Med 1987;28:1383-1392.
25.
Geyskes GG, Oei HY, Klinge J, et al: Renovascular hy pertension. The small kidney updated. Q J Med 1988;251:203-217.
26.
Wenting GJ, Tan-Tjiong HL, Derkx FHM, et al: Split renal functions after Captopril in unilateral renal artery stenosis. Br Med J 1984; 288:886-890. Nally JV, Jr., Bedoya LA, Park CH, et al: Captopril-stimulated renography versus renal vein renins in two-kid ney, two-clip hypertension, in Blaufox MD, Hollenberg NK, Raynayd C (eds): Radionuclides in Nephro-Urology, Contributions to Nephrology, Vol. 79. Basel, Karger, 1990, pp 176-180.
15.
Farmelant MH, Burrows BA: The renogram: physiologic basis and current clinical use. Semin Nucl Med 1974;4:61-72. 16. Sfakianakis GN, Sfakianaki E, Bourgoignie J: Renal scin tigraphy following angiotensin converting enzyme inhi bition in the diagnosis of renovascular hypertension (Captopril scintigraphy), in Freeman LM (ed): Nuclear Medicine Annual. New York, Raven Press, 1988, pp 125-170. 17. Cuocolo A, Esposito S, Volpe M, Celentano L, et al: Renal artery stenosis detection by combined Gates' technique and Captopril test in hypertensive patients. J Nucl Med 1989;30:51-56.
27.
Itoh K, Shinohara M, Togashi M, Koyanagi T: Captopril renal scintigraphy in a patient with bilateral renal artery stenosis. J Nucl Med 1989;30:2042-2045.
28.
Fommei E, Bellina R, Berteiii P, et al: Interactive func tional imaging of renal scintigraphy after Captopril in the detection of global and segmental hypoperfusion, in Bis chof-Delaloye A, Blaufox MD (eds): Radianuclides in Nephrology, Contributions to Nephrology, Vol. 56. Basel, Karger, 1987, pp 111-116.
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Thorstad BL, Russell CD, Dubovsky EV, Keller FS, et al: Abnormal Captopril renogram with a technetium-99mlabeled hippuran analog. J Nucl Med 1988;29:17301737. 11. Geyskes GG, Oei HY, Puylaert CBAJ, Dorhout Mees EJ: Renovascular hypertension identified by captopril-induced changes in the renogram. Hypertension 1987;9:451-458. 12. Oei HY, Geyskes GG, Dorhout Mees EJ, Puylaert CBAJ: The significance of Captopril renography in renovascular hypertension, in Bischof-Delaloye A, Blaufox MD (eds): Radionuclides in Nephrology, Contributions to Nephrol ogy, Vol. 56. Basel, Karger, 1987, pp 95-103.
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