Nephrol Dial Transplant (1992) 7: 211-215 £ 1992 European Dialysis and Transplant Association-European Renal Association
Nephrology Dialysis Transplantation
Original Article
Screening for renovascular disease with captopril-enhanced renography A. G. McLean, A. J. W. Hilson, J. E. Scoble, E. R. Maher, D. S. Thakrar, J. F. Moorhead and P. Sweny Department of Nephrology and Transplantation, and Department of Nuclear Medicine, Royal Free Hospital, London, UK.
Abstract. Changes in renal function caused by angiotensin-converting-enzyme (ACE) inhibitors can be detected on " T c - D T P A renography so that DTPA scanning before and after a single dose of captopril can be used to screen for renovascular disease. We have performed captopril-DTPA scans with renal arteriography on 104 patients, of whom 27 had renal artery stenosis, all due to atheroma. Using a 5% fall in divided function or a delay of > 15 min in time to peak activity on one side after captopril, or the finding of > 90% divided function on one side before captopril as criteria for a positive scan, a sensitivity of 93% and specificity of 70% was achieved. The negative predictive value of the test in our population was 93%. Bilateral improvement in renographic function after captopril was seen in patients with accelerated phase hypertension. The presence of bilateral renal artery disease did not reduce the sensitivity of the test, but sensitivity was reduced (75%) in patients with renal impairment. Clinical characteristics in our patients most strongly associated with renal artery stenosis were abdominal bruit, recurrent left ventricular failure, and peripheral vascular disease. In view of the well-publicized risks of ACE inhibitor therapy, care should be exercised in the use of these agents in such patients. Key words: captopril-diagnostic use; DTPA renography; renovascular disease
Introduction Atheromatous disease of the renal arteries is common, and although in many cases it causes neither hypertension nor renal impairment [1,2] it is a significant cause of hypertension that is difficult to control, and of renal failure, both chronic (through bilateral renal artery obstruction) and acute (following the use of angiotensin-converting-enzyme inhibitors in the presence of bilateral disease) [3,4]. Haemodynamically significant renal artery stenosis causes renin secretion with intrarenal production of angiotensin II which causes efferent arteriolar vasoconstriction, maintaining transglomerular pressure and preserving glomerular filtration. Interruption of this homeostatic mechanism leads to a fall in glomerular filtration and altered renal haemodynamics [5]. These changes can be detected on radioisotope renography by changes in divided function, derived single-kidney GFR, parenchymal transit time, and time to peak activity [6-9]. Divided function and time to peak activity are the easiest parameters to derive from renographic curves and we have used them to measure changes in DTPA renograms before and after a single dose of captopril to screen for renal artery stenosis, in order to test the usefulness of captopril-DTPA scanning as a screening test in everyday clinical practice.
Subjects and methods Patients
Correspondence and offprint requests to: Dr Adam McLean, Garden Flat, 29A South Villas, London NW1 9BT, UK.
One hundred and four hypertensive patients underwent DTPA scanning before and after captopril followed by
A. G. McLean el al.
212
angiography. The patients were referred for investigation from nephrology, cardiology, and vascular surgery clinics because of clinical suspicion of renovascular disease. Sixtyone men and 43 women were studied with a mean age of 57 years (range 20-80). No patients who had undergone both captopril-DTPA scanning and angiography were excluded from analysis. The presence of abdominal bruits, history of recurrent heart failure, signs and symptoms of peripheral vascular disease, history of ischaemic heart disease or cerebrovascular disease, history of diabetes, smoking history, serum creatinine prior to investigation, and change in blood pressure with captopnl administration were recorded in all subjects.
conventional arterial angiography of which one study was performed at another hospital. Angiograms were reported within the Radiology Department at the Royal Free Hospital and were taken as positive if any degree of renal artery stenosis was demonstrated. There was significant morbidity associated with angiography, with three patients with previously impaired renal function requiring dialysis after angiography because of a combination of deterioration in renal function due to contrast nephrotoxicity and volume overload. One of these, a 73-year-old man with widespread severe atheromatous disease, died before dialysis was instituted.
Captopril renography
Results
"Tc-DTPA renography was performed in the Department of Nuclear Medicine at the Royal Free Hospital. Scans without, and after captopril were performed on consecutive days. Antihypertensive medication was not altered prior to scanning but referring physicians were advised to avoid salt and water depletion in their patients prior to captopril administration and patients with uncontrolled hypertension (systolic BP > 190mmHg, diastolic BP > llOmmHg) had their post-captopril scans deferred until control was adequate to minimize the risk of precipitous falls in blood pressure following captopril. Where possible, similar doses of radioactive tracer were used in the two scans to allow semiquantative comparison of the renographic curves. Post-captopril renography was performed 1 h following oral administration of 25 mg of captopril. Blood pressure was measured at 15 min intervals from before the captopril was taken until the end of the test. Staff and equipment were available for administration of i.v. saline in the event of hypotension following ACE inhibition. In elderly patients and those thought to be at risk from hypotension because of volume depletion or marked asymmetry of function on scanning without captopril, an i.v. drip was set up prior administration of captopril. In five patients who were receiving captopril for control of their hypertension prior to investigation, scanning was performed initially on their normal medication and then after stopping captopril for 48 h. Scans before and after captopril were interpreted without knowledge of angiographic findings and were taken as positive if they had been interpreted as suggesting renovascular disease at the time they were performed. A pilot study, data from which are included in these results [10], indicated that a fall of 5% in divided function on one side after captopril provided the most discriminating marker for a renal artery stenosis. Accumulated experience of interpreting the scans and data from other studies [9] showed that the time to peak activity on the renographic curves (a non-physiological variable reflecting the point at which loss of tracer from the kidney in the urine exceeds acquisition of tracer from the blood) was markedly prolonged in patients with renovascular disease, and this was adopted as a criterion for a positive scan. Semiquantitative analysis of the renographic curves showed that in some cases the uptake of tracer was improved bilaterally after captopril and where such improvements were unequal, changes in divided function occurred. Scans showing this pattern were interpreted as negative despite changes of >5% in divided function. Angiography Seventy-four patients underwent i.\. digital subtraction angiography (IVDSA), 25 intra-arterial DSA. and five had
Twenty-seven patients had renal artery stenosis on angiography, of whom six had bilateral disease. Twenty-three of these cases were positively identified by DTPA scanning before and after captopril including five of the cases with bilateral disease. Fifty-six patients had negative scans confirmed by angiography, four patients had false negative scans and 22 had false positive scans (Figure 1). The sensitivity of the test was 85% (23/27) and the specificity was 72% (56/78). If the finding of > 9 0 % of divided function on one side on the initial scan was taken as indicative of a positive scan, the sensitivity increased to 93% (25/27) with sensitivity of 70% (52/74). The negative predictive value of a negative captopril-DTPA test was 93% (56/60) in this population. Of the two patients with false negative scans, both had significant renal impairment with creatinine concentrations >400 umol/1; one also had bilateral disease but both had significant renal artery disease with > 50% stenosis on angiography. Analysis of the clinical characteristics of the patients (Figure 2) showed that abdominal bruits, previous recurrent heart failure, and the presence of peripheral vascular disease were the strongest predictors of the presence of renovascular disease. Of the characteristics not shown in the Figure, 40 patients were smokers, of whom 18 had positive angiograms, and 18 had a past history of ischaemic heart disease or cerebrovascular disease, of whom seven had positive angiograms. Twenty-one patients had a fall in systolic blood pressure of > 30 mmHg, of whom seven had positive angiograms. Twenty-six of the patients had abnormal renal function with serum creatinines of > 120 umol/l. Four of these had renovascular disease at angiography, of which three were correctly identified by captoprilDTPA scanning (sensitivity 75%). Six patients had >90% of renal function provided by one kidney on initial renography and four of these had renal artery stenosis. Of the 25 true positive captopril-DTPA scans, 16 were identified by a > 5% fall in divided function
213
Screening for rcnovascular disease with captopril-DTPA scan DELAY IN TIME TO PEAK ACTIVITY ON DTPA SCAN AFTER CAPTOPRIL
1
1
\
I 1
>15 MINUTES
1
1
1
!•
•
•
A o
KM
K>
i"
POSITIVE ANGIOGRAM
NUMBIR OF PATIENTS
% POSITIVE FIR. 2. Fa-quer.cy' of renal artery stenosis in patients in different sub-groups. (Refractory hypertension = patients on three or more drugs. Renal impairment = plasma creatininc > 120 pnol I.J.
following captopril, four by increased time to peak activity and three by both criteria; the remaining two scans were identified as positive on the basis of > 90% divided function on one side in the pre-captopril scan,
Six patients showed bilateral improvement in renographic renal function after captopril, leading to a >5% fall in divided function on one side. None of these had renal artery stenosis on angiography but
214
four were patients who had presented with accelerated phase hypertension. Morbidity of the procedure was low. Twenty-one subjects experienced a fall in systolic blood pressure of > 30 mmHg, of whom eight experienced a fall of > 50 mmHg but in all cases, this was promptly reversed by saline infusion.
Discussion The detection of renovascular hypertension and of individuals at risk of renal failure due to atheromatous disease is hampered by several problems: the incidence of renovascular hypertension is low in the hypertensive population [11] and the presence of renal artery atheroma in normotensive individuals suggests that much of the anatomically identifiable renal artery stenosis in hypertensives is not haemodynamically significant. At the moment the only true method of diagnosing renovascular hypertension is by demonstrating a sustained reduction in blood pressure after intervention to remove the renal artery stenosis. Furthermore, although it is known that renal artery atheroma is a progressive condition [12] the natural history is poorly understood especially in the context of patients on angiotensin-converting enzyme inhibitors, while the nature of the relationship over time between hypertension and renal artery stenosis is complicated by the association between hypertension and accelerated atheroma formation in general, and renal arteriosclerosis in particular. Of the currently available techniques that might be used for screening the section of the hypertensive population who have clinical characteristics suggestive of renovascular hypertension, IVDSA and IADSA give only anatomical information and carry the risk of contrast nephrotoxicity. It would be desirable to have an initial screening test to reduce the number of individuals going forward to angiography, which is the necessary prelude to intervention. Measurements of renal vein renin values give some predictive information but are invasive, and measurement of changes in peripheral plasma renin activity after administration of captopril requires careful control of the patient's medication and sodium balance to give reliable results [13]. Duplex Doppler and MR1 scanning are dependent on skilled operators and scarce equipment and are still at an experimental stage of evaluation. [14,15]. Intravenous pyelography and plain radioisotope renography both show specific abnormalities in some cases of renovascular disease, but lack the sensitivity required for useful screening procedures. Captopril-DTPA scanning has, in our hands, been safe, reliable and simple. The high negative predictive value makes it a worthwhile screening procedure. The
A. G. McLean el at.
high sensitivity of the test in this series poses a problem in that most of the anatomically identifiable stenoses were detected by renography despite the fact that much renovascular disease is believed to be incidental to coexisting essential hypertension. This may be due to the selected nature of the population we studied, which may have excluded most of the incidental renovascular disease, but it is probable that the captopril-DTPA test was detecting some stenoses that were sufficiently haemodynamically significant to activate intrarenal renin-angiotensin production but not severe enough to contribute to systemic hypertension. A current European trial is addressing the important issue of whether a positive captopril-DTPA test predicts a good blood pressure response to revascularization, and one smaller study has already suggested that this may be the case [16]. Several smaller previous studies have shown the sensitivity of captopril-DTPA scanning, mostly in patients who had already undergone angiography (reviewed in [17]). The finding of one group, that a single DTPA scan following captopril without a baseline scan provided adequate diagnostic information in most cases [18], was not confirmed in our data in which the only diagnostic abnormality in over half of our patients with renovascular disease was the change in divided renal function between the baseline scan and that following captopril. One study has suggested that cortical retention of 131 I-hippuran after administration of frusemide and ACE inhibitor gives more sensitive detection of renal artery stenosis than renographic changes detected on DTPA scanning, especially in the context of renal impairment [19]. However, another recent study found orthoiodohippurate scanning to be slightly less sensitive than captopril scanning [20], while confirming the finding that a difference in retention of tracer activity at 15 min as a fraction of peak activity of > 20% served as an additional criterion for defining positive DTPA scans post-captopril. Analysis of our data using this additional criterion did not result in improved sensitivity. Our findings demonstrate that compared to other available modalities for screening a high-risk population for renovascular disease the captopril-DTPA scan is a sensitive and robust screening procedure for renal artery stenosis under normal clinical conditions. It gives reliable results from interpretation of preand post-captopril scans without the necessity for either complex analysis of scan data or rigorous standardization of test conditions in terms of the patients' fluid and sodium balance, protein intake, or antihypertensive drug regime. This allows the early use of captopril scanning in patients presenting with hypertension and moderate renal impairment, redu-
Screening for renovascular disease with captopril-DTPA scan
cing the need to perform angiography in this group who are at increased risk of suffering morbidity from invasive radiographic techniques involving contrast media. Our data suggest that before prescribing ACE inhibitors to hypertensive patients who have evidence of peripheral vascular disease, have had recurrent episodes of heart failure, or have abdominal bruits, physicians should consider referral for investigation of possible renovascular disease or, as a minimum, should measure renal function before and after starting converting-enzyme inhibitor therapy.
215
8.
9. 10.
11. 12.
References 1. HoUey KE, Hunt JC, Brown AL Jr, Kinkaid OW, Sheps SC. Renal artery stenosis: A clinicopathologic study in normotensive and hypertensive patients. Am J Med 1964; 37: 14-22 2. Eyler WR, Clark MD, Garman JE, Rian RL, Meninger PE. Angiography of renal areas including a study of renal artery stenosis in patients with or without hypertension. Radiology 1962; 78: 879-892 3. Besarab A, Brown RS, Rubin NT et al. Reversible renal failure following bilateral renal occlusive disease: clinical features, pathology, and the role of surgical revascularisation. J Am MedAssoc 1976; 235: 2838-2841 4. Hricik DE, Browning PJ, Kopelman R, Goorno WE, Madias NG, Dzau VJ. Captropril-induced functional renal insufficiency in patients with bilateral renal-artery stenosis or renal artery stenosis in a solitary kidney. N Engl J Med 1983; 308: 373-376 5. Levenson DJ, Dzau VJ. Effects of angiotensin converting enzyme inhibition on renal hemodynamics in renal artery stenosis. Kidney Im 1987; 31 [Suppl. 20]: SI73-179 6. Wenting GJ, Tan-Tjiong HL, Derkx FH, de-Bruyn JH, ManInt-Veld AJ, Schalekand MA. Split renal function after captopril in unilateral renal artery stenosis. Br Med J 1984; 288: 886-890 7. Wilcox CS, Smith TB, Frederickson ED, Wingo CD, Phillipe MI, Williams CM. The captopril glomerular filtration rate
13. 14.
15. 16. 17.
18.
19.
20.
renogram in renovascular hypertension. Clin Nucl Med 1989; 14: 1-7 Sfakianakis GN, Bourgoignie JJ, Jaffe D, Kyriakides G, PerezStable E, Duncan RC. Single dose captopril scintigraphy in the diagnosis of rcnovascular h>pcrtcnsion. J Nucl Med 1987; 28: 1383-1392 Geyskes GG, Oei HY, Faber JA. Renography: prediction of blood pressure after dilatation of renal artery stenosis. Sephron 1986; 44 [Suppl 7]: 54-99 Maher ER, Othman S, Frankel AH, Sweny P, Moorhead JF, Hilson AJW. Captopril-enhanced Wm Tc DTPA scintigraphy in the detection of renal artery stenosis. Nephrol Dial Transplant 1988; 3: 608-611 Horvath JS, Waugh RC, Tiller DJ, Duggin GG. The detection of renovascular hypertension: a study of 490 patients by renal angiography. Q J Med 1982; 51: 139-146 Wollenweber J, Sheps SG, Davis GD. Clinical course of atherosclerotic renovascular disease. Am J Cardiol 1968; 21: 60-71 McCarthy JE, Weder AB. The captopril test and renovascular hypertension. A cautionary tale. Arch Intern Med 1990, 150: 493-495 Berland LL, Koslin DB, Routh WD, Keller FS. Renal artery stenosis: prospective evaluation of diagnosis with color duplex US compared with angiography. Work in progress. Radiology 1990; 174:421-423 Kim D, Edelman RR, Kent KC, Porter DH, Skillman JJ. Abdominal aorta and renal artery stenosis: evaluation with MR angiography. Radiology 1990; 174: 727-731 Meier GH, Sumpio B, Black HR, Gusberg RJ. Captopril renal scintigraphy—an advance in the detection and treatment of renovascular hypertension. J Vase Surg 1990; 11: 770-777 Peters AM. Renal artery stenosis, renc-vascular hypertension and predicting the blood pressure response to renal revascularization. Nucl Med Comm 1990; 11: 1-5 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 Erbsloh-Moller B, Dumas A, Roth D, Sfakianakis GN, Bourgoignie JJ. Furosemide- 131 I-hippuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension. Am J Med 1991; 90: 23-29 Mann SJ, Pickering TG, Sos TA et al. Captopril renography in the diagnosis of renal artery stenosis: accuracy and limitations. Am J Med 1991; 90:
Received for publication 19.2.91 Accepted in revised form 9.8.91
Nephrology Dialysis Transplantation
Original Article
Screening for renovascular disease with captopril-enhanced renography A. G. McLean, A. J. W. Hilson, J. E. Scoble, E. R. Maher, D. S. Thakrar, J. F. Moorhead and P. Sweny Department of Nephrology and Transplantation, and Department of Nuclear Medicine, Royal Free Hospital, London, UK.
Abstract. Changes in renal function caused by angiotensin-converting-enzyme (ACE) inhibitors can be detected on " T c - D T P A renography so that DTPA scanning before and after a single dose of captopril can be used to screen for renovascular disease. We have performed captopril-DTPA scans with renal arteriography on 104 patients, of whom 27 had renal artery stenosis, all due to atheroma. Using a 5% fall in divided function or a delay of > 15 min in time to peak activity on one side after captopril, or the finding of > 90% divided function on one side before captopril as criteria for a positive scan, a sensitivity of 93% and specificity of 70% was achieved. The negative predictive value of the test in our population was 93%. Bilateral improvement in renographic function after captopril was seen in patients with accelerated phase hypertension. The presence of bilateral renal artery disease did not reduce the sensitivity of the test, but sensitivity was reduced (75%) in patients with renal impairment. Clinical characteristics in our patients most strongly associated with renal artery stenosis were abdominal bruit, recurrent left ventricular failure, and peripheral vascular disease. In view of the well-publicized risks of ACE inhibitor therapy, care should be exercised in the use of these agents in such patients. Key words: captopril-diagnostic use; DTPA renography; renovascular disease
Introduction Atheromatous disease of the renal arteries is common, and although in many cases it causes neither hypertension nor renal impairment [1,2] it is a significant cause of hypertension that is difficult to control, and of renal failure, both chronic (through bilateral renal artery obstruction) and acute (following the use of angiotensin-converting-enzyme inhibitors in the presence of bilateral disease) [3,4]. Haemodynamically significant renal artery stenosis causes renin secretion with intrarenal production of angiotensin II which causes efferent arteriolar vasoconstriction, maintaining transglomerular pressure and preserving glomerular filtration. Interruption of this homeostatic mechanism leads to a fall in glomerular filtration and altered renal haemodynamics [5]. These changes can be detected on radioisotope renography by changes in divided function, derived single-kidney GFR, parenchymal transit time, and time to peak activity [6-9]. Divided function and time to peak activity are the easiest parameters to derive from renographic curves and we have used them to measure changes in DTPA renograms before and after a single dose of captopril to screen for renal artery stenosis, in order to test the usefulness of captopril-DTPA scanning as a screening test in everyday clinical practice.
Subjects and methods Patients
Correspondence and offprint requests to: Dr Adam McLean, Garden Flat, 29A South Villas, London NW1 9BT, UK.
One hundred and four hypertensive patients underwent DTPA scanning before and after captopril followed by
A. G. McLean el al.
212
angiography. The patients were referred for investigation from nephrology, cardiology, and vascular surgery clinics because of clinical suspicion of renovascular disease. Sixtyone men and 43 women were studied with a mean age of 57 years (range 20-80). No patients who had undergone both captopril-DTPA scanning and angiography were excluded from analysis. The presence of abdominal bruits, history of recurrent heart failure, signs and symptoms of peripheral vascular disease, history of ischaemic heart disease or cerebrovascular disease, history of diabetes, smoking history, serum creatinine prior to investigation, and change in blood pressure with captopnl administration were recorded in all subjects.
conventional arterial angiography of which one study was performed at another hospital. Angiograms were reported within the Radiology Department at the Royal Free Hospital and were taken as positive if any degree of renal artery stenosis was demonstrated. There was significant morbidity associated with angiography, with three patients with previously impaired renal function requiring dialysis after angiography because of a combination of deterioration in renal function due to contrast nephrotoxicity and volume overload. One of these, a 73-year-old man with widespread severe atheromatous disease, died before dialysis was instituted.
Captopril renography
Results
"Tc-DTPA renography was performed in the Department of Nuclear Medicine at the Royal Free Hospital. Scans without, and after captopril were performed on consecutive days. Antihypertensive medication was not altered prior to scanning but referring physicians were advised to avoid salt and water depletion in their patients prior to captopril administration and patients with uncontrolled hypertension (systolic BP > 190mmHg, diastolic BP > llOmmHg) had their post-captopril scans deferred until control was adequate to minimize the risk of precipitous falls in blood pressure following captopril. Where possible, similar doses of radioactive tracer were used in the two scans to allow semiquantative comparison of the renographic curves. Post-captopril renography was performed 1 h following oral administration of 25 mg of captopril. Blood pressure was measured at 15 min intervals from before the captopril was taken until the end of the test. Staff and equipment were available for administration of i.v. saline in the event of hypotension following ACE inhibition. In elderly patients and those thought to be at risk from hypotension because of volume depletion or marked asymmetry of function on scanning without captopril, an i.v. drip was set up prior administration of captopril. In five patients who were receiving captopril for control of their hypertension prior to investigation, scanning was performed initially on their normal medication and then after stopping captopril for 48 h. Scans before and after captopril were interpreted without knowledge of angiographic findings and were taken as positive if they had been interpreted as suggesting renovascular disease at the time they were performed. A pilot study, data from which are included in these results [10], indicated that a fall of 5% in divided function on one side after captopril provided the most discriminating marker for a renal artery stenosis. Accumulated experience of interpreting the scans and data from other studies [9] showed that the time to peak activity on the renographic curves (a non-physiological variable reflecting the point at which loss of tracer from the kidney in the urine exceeds acquisition of tracer from the blood) was markedly prolonged in patients with renovascular disease, and this was adopted as a criterion for a positive scan. Semiquantitative analysis of the renographic curves showed that in some cases the uptake of tracer was improved bilaterally after captopril and where such improvements were unequal, changes in divided function occurred. Scans showing this pattern were interpreted as negative despite changes of >5% in divided function. Angiography Seventy-four patients underwent i.\. digital subtraction angiography (IVDSA), 25 intra-arterial DSA. and five had
Twenty-seven patients had renal artery stenosis on angiography, of whom six had bilateral disease. Twenty-three of these cases were positively identified by DTPA scanning before and after captopril including five of the cases with bilateral disease. Fifty-six patients had negative scans confirmed by angiography, four patients had false negative scans and 22 had false positive scans (Figure 1). The sensitivity of the test was 85% (23/27) and the specificity was 72% (56/78). If the finding of > 9 0 % of divided function on one side on the initial scan was taken as indicative of a positive scan, the sensitivity increased to 93% (25/27) with sensitivity of 70% (52/74). The negative predictive value of a negative captopril-DTPA test was 93% (56/60) in this population. Of the two patients with false negative scans, both had significant renal impairment with creatinine concentrations >400 umol/1; one also had bilateral disease but both had significant renal artery disease with > 50% stenosis on angiography. Analysis of the clinical characteristics of the patients (Figure 2) showed that abdominal bruits, previous recurrent heart failure, and the presence of peripheral vascular disease were the strongest predictors of the presence of renovascular disease. Of the characteristics not shown in the Figure, 40 patients were smokers, of whom 18 had positive angiograms, and 18 had a past history of ischaemic heart disease or cerebrovascular disease, of whom seven had positive angiograms. Twenty-one patients had a fall in systolic blood pressure of > 30 mmHg, of whom seven had positive angiograms. Twenty-six of the patients had abnormal renal function with serum creatinines of > 120 umol/l. Four of these had renovascular disease at angiography, of which three were correctly identified by captoprilDTPA scanning (sensitivity 75%). Six patients had >90% of renal function provided by one kidney on initial renography and four of these had renal artery stenosis. Of the 25 true positive captopril-DTPA scans, 16 were identified by a > 5% fall in divided function
213
Screening for rcnovascular disease with captopril-DTPA scan DELAY IN TIME TO PEAK ACTIVITY ON DTPA SCAN AFTER CAPTOPRIL
1
1
\
I 1
>15 MINUTES
1
1
1
!•
•
•
A o
KM
K>
i"
POSITIVE ANGIOGRAM
NUMBIR OF PATIENTS
% POSITIVE FIR. 2. Fa-quer.cy' of renal artery stenosis in patients in different sub-groups. (Refractory hypertension = patients on three or more drugs. Renal impairment = plasma creatininc > 120 pnol I.J.
following captopril, four by increased time to peak activity and three by both criteria; the remaining two scans were identified as positive on the basis of > 90% divided function on one side in the pre-captopril scan,
Six patients showed bilateral improvement in renographic renal function after captopril, leading to a >5% fall in divided function on one side. None of these had renal artery stenosis on angiography but
214
four were patients who had presented with accelerated phase hypertension. Morbidity of the procedure was low. Twenty-one subjects experienced a fall in systolic blood pressure of > 30 mmHg, of whom eight experienced a fall of > 50 mmHg but in all cases, this was promptly reversed by saline infusion.
Discussion The detection of renovascular hypertension and of individuals at risk of renal failure due to atheromatous disease is hampered by several problems: the incidence of renovascular hypertension is low in the hypertensive population [11] and the presence of renal artery atheroma in normotensive individuals suggests that much of the anatomically identifiable renal artery stenosis in hypertensives is not haemodynamically significant. At the moment the only true method of diagnosing renovascular hypertension is by demonstrating a sustained reduction in blood pressure after intervention to remove the renal artery stenosis. Furthermore, although it is known that renal artery atheroma is a progressive condition [12] the natural history is poorly understood especially in the context of patients on angiotensin-converting enzyme inhibitors, while the nature of the relationship over time between hypertension and renal artery stenosis is complicated by the association between hypertension and accelerated atheroma formation in general, and renal arteriosclerosis in particular. Of the currently available techniques that might be used for screening the section of the hypertensive population who have clinical characteristics suggestive of renovascular hypertension, IVDSA and IADSA give only anatomical information and carry the risk of contrast nephrotoxicity. It would be desirable to have an initial screening test to reduce the number of individuals going forward to angiography, which is the necessary prelude to intervention. Measurements of renal vein renin values give some predictive information but are invasive, and measurement of changes in peripheral plasma renin activity after administration of captopril requires careful control of the patient's medication and sodium balance to give reliable results [13]. Duplex Doppler and MR1 scanning are dependent on skilled operators and scarce equipment and are still at an experimental stage of evaluation. [14,15]. Intravenous pyelography and plain radioisotope renography both show specific abnormalities in some cases of renovascular disease, but lack the sensitivity required for useful screening procedures. Captopril-DTPA scanning has, in our hands, been safe, reliable and simple. The high negative predictive value makes it a worthwhile screening procedure. The
A. G. McLean el at.
high sensitivity of the test in this series poses a problem in that most of the anatomically identifiable stenoses were detected by renography despite the fact that much renovascular disease is believed to be incidental to coexisting essential hypertension. This may be due to the selected nature of the population we studied, which may have excluded most of the incidental renovascular disease, but it is probable that the captopril-DTPA test was detecting some stenoses that were sufficiently haemodynamically significant to activate intrarenal renin-angiotensin production but not severe enough to contribute to systemic hypertension. A current European trial is addressing the important issue of whether a positive captopril-DTPA test predicts a good blood pressure response to revascularization, and one smaller study has already suggested that this may be the case [16]. Several smaller previous studies have shown the sensitivity of captopril-DTPA scanning, mostly in patients who had already undergone angiography (reviewed in [17]). The finding of one group, that a single DTPA scan following captopril without a baseline scan provided adequate diagnostic information in most cases [18], was not confirmed in our data in which the only diagnostic abnormality in over half of our patients with renovascular disease was the change in divided renal function between the baseline scan and that following captopril. One study has suggested that cortical retention of 131 I-hippuran after administration of frusemide and ACE inhibitor gives more sensitive detection of renal artery stenosis than renographic changes detected on DTPA scanning, especially in the context of renal impairment [19]. However, another recent study found orthoiodohippurate scanning to be slightly less sensitive than captopril scanning [20], while confirming the finding that a difference in retention of tracer activity at 15 min as a fraction of peak activity of > 20% served as an additional criterion for defining positive DTPA scans post-captopril. Analysis of our data using this additional criterion did not result in improved sensitivity. Our findings demonstrate that compared to other available modalities for screening a high-risk population for renovascular disease the captopril-DTPA scan is a sensitive and robust screening procedure for renal artery stenosis under normal clinical conditions. It gives reliable results from interpretation of preand post-captopril scans without the necessity for either complex analysis of scan data or rigorous standardization of test conditions in terms of the patients' fluid and sodium balance, protein intake, or antihypertensive drug regime. This allows the early use of captopril scanning in patients presenting with hypertension and moderate renal impairment, redu-
Screening for renovascular disease with captopril-DTPA scan
cing the need to perform angiography in this group who are at increased risk of suffering morbidity from invasive radiographic techniques involving contrast media. Our data suggest that before prescribing ACE inhibitors to hypertensive patients who have evidence of peripheral vascular disease, have had recurrent episodes of heart failure, or have abdominal bruits, physicians should consider referral for investigation of possible renovascular disease or, as a minimum, should measure renal function before and after starting converting-enzyme inhibitor therapy.
215
8.
9. 10.
11. 12.
References 1. HoUey KE, Hunt JC, Brown AL Jr, Kinkaid OW, Sheps SC. Renal artery stenosis: A clinicopathologic study in normotensive and hypertensive patients. Am J Med 1964; 37: 14-22 2. Eyler WR, Clark MD, Garman JE, Rian RL, Meninger PE. Angiography of renal areas including a study of renal artery stenosis in patients with or without hypertension. Radiology 1962; 78: 879-892 3. Besarab A, Brown RS, Rubin NT et al. Reversible renal failure following bilateral renal occlusive disease: clinical features, pathology, and the role of surgical revascularisation. J Am MedAssoc 1976; 235: 2838-2841 4. Hricik DE, Browning PJ, Kopelman R, Goorno WE, Madias NG, Dzau VJ. Captropril-induced functional renal insufficiency in patients with bilateral renal-artery stenosis or renal artery stenosis in a solitary kidney. N Engl J Med 1983; 308: 373-376 5. Levenson DJ, Dzau VJ. Effects of angiotensin converting enzyme inhibition on renal hemodynamics in renal artery stenosis. Kidney Im 1987; 31 [Suppl. 20]: SI73-179 6. Wenting GJ, Tan-Tjiong HL, Derkx FH, de-Bruyn JH, ManInt-Veld AJ, Schalekand MA. Split renal function after captopril in unilateral renal artery stenosis. Br Med J 1984; 288: 886-890 7. Wilcox CS, Smith TB, Frederickson ED, Wingo CD, Phillipe MI, Williams CM. The captopril glomerular filtration rate
13. 14.
15. 16. 17.
18.
19.
20.
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Received for publication 19.2.91 Accepted in revised form 9.8.91
