Applied Radiology

Dr. Taylor is with the Department of Radiology at Emory University Hospital, Atlanta, GA.

R enovascular disease can be divided into three categories: 1) renal artery stenosis, 2) ischemic nephropathy, and 3) renovascular hypertension. Renal artery stenosis is common in non-hypertensive elderly persons and is an associated, but non-etiologic, finding in a number of hypertensive patients. ¹ Ischemic nephropathy refers to a loss of renal function due to progressive severe occlusive disease of the extraparenchymal renal artery. Renovascular hypertension (RVH) describes an elevated blood pressure due to anatomic stenosis of the renal artery, a reduction of perfusion pressure distal to the stenosis, and activation of the renin-angiotensin system. RVH is estimated to affect <1% to 3% of the unselected hypertension population and up to 15% to 30% of patients referred to a subspecialty center because of refractory hypertension. ^2,3 The strength of ACE (angiotensin converting enzyme) inhibition renography is that it is the only widely available imaging procedure that directly tests for the presence of renovascular hypertension; other imaging procedures examine only for the presence of renal artery stenosis.

Who is at risk for renovascular hypertension?

Clinical features associated with a moderate or high risk of renovascular hypertension include abrupt onset of hypertension in patients under age 30 or over age 55, grade 3 or 4 hypertensive retinopathy, severe hypertension resistant to medical therapy in a compliant patient, bruits in the abdomen or flank, occlusive disease in other vascular beds, and unexplained azotemia or worsening renal function during ACE inhibitor therapy. In patients with a very low likelihood of RVH, diagnostic imaging tests to detect renovascular hypertension are not indicated; the prevalence of the disease is simply too low for any test to be cost effective.

Guideline development for ACE inhibition renography

A review of ACE inhibition renography literature over the past 10 years revealed that the protocols for the performance of ACE inhibition renography and the criteria for findings indicative of renovascular hypertension varied from center to center. The lack of standardization, coupled with the fact that many studies used stenosis of the renal artery rather than blood pressure response to revascularization (i.e., true renovascular hypertension) as the end point, often made it difficult to draw definitive conclusions. In an attempt to address these issues, an international consensus committee on ACE inhibitor renography was established by the Ninth International Symposium of Radionuclides in Nephrourology. Their consensus report was published in 1996. ² Members of the original consensus committee, with the addition of Alain Prigent, MD, recently updated the Society of Nuclear Medicine (SNM) Guideline on ACE inhibitor renography. ⁴ This guideline can now be downloaded from the Society of Nuclear Medicine website at SNM.org. The 1996 Consensus Report, ² the 1999 SNM ACE inhibition guideline for the detection of renovascular hypertension, and a recent article in Seminars of Nuclear Medicine ⁵ form the basis of the following discussion and recommendations.

Pathophysiology of renovascular hypertension and ACE inhibition renography

Renovascular hypertension depends on secretion of renin from the juxta-glomerular apparatus of the underperfused, stenotic kidney. ACE inhibition interrupts the renin-angiotensin system by preventing the conversion of angio-
tensin I to angiotensin II, such that the vasoconstrictor and aldosterone-stimulating effects of angiotensin II are blocked. Within the stenotic kidney, inhibition of the enzyme reduces the angiotensin II-dependent constriction of the postglomerular arteriole, thereby lowering the transcapillary forces that maintain glomerular filtration. This decrease in individual kidney glomerular filtration can be assessed noninvasively by radionuclide renography.

Alternative diagnostic tests

Conventional angiography and digital subtraction angiography (DSA) are
the gold standards for the diagnosis of renal artery stenosis (not necessarily renovascular hypertension), but they are invasive and relatively expensive, and subject the kidney to a contrast load. Thus, they are less useful as screening exams, especially in patients with poor renal function. CT angiography is noninvasive but also subjects the kidney to a contrast load. The 1996 American College of Radiology Appropriateness Criteria lists ACE inhibition renography or Duplex sonography as the most appropriate initial exams in patients with compromised renal function. Duplex sonography is noninvasive but the test can be quite time consuming to perform and it has achieved reliability only at certain dedicated centers due to difficulties inherent in performing and interpreting the exam. MR angiography is gaining wider appeal due to its noninvasive nature and lack of iodinated contrast, but MR angiography does not appear to be sensitive for segmental or distal renal artery stenosis. It may be more useful in older patients who are most likely to have proximal renal artery stenosis.

Other tests (such as renal vein renin sampling, hypertensive IVU, and intravenous digital subtraction angiography) are not appropriate as screening procedures, although renal vein renin assays and ACE inhibitor renography can be used to evaluate the significance of a renal artery stenosis. The captopril test (stimulated plasma renin following captopril administration) has a low sensitivity of approximately 60% for RVH and its accuracy decreases as the prevalence of RVH increases in the patient population. ^6,7

Which radiopharmaceutical should be used for ACE inhibition renography?

In patients with azotemia, tubular agents such as MAG3 or I-123 OIH are considered to be the agents of choice. ^2,8 In patients with normal renal function, MAG3 and DTPA give comparable results. ⁹

Should patients be hydrated?

Dehydration can prolong the excretory phase of the renogram curve and reduce the specificity of the study. Patients should be instructed to arrive well hydrated. Many centers also have the patient drink 5 to 10 mL/kg of water on arrival in the department, preferably 30 to 60 minutes before the study. Finally, if a two-stage ACE inhibition examination is scheduled, it is important to continue hydration between the studies.

Which medications interfere with ACE inhibition renography?

ACE inhibitors --Chronic ACE inhibition may reduce the sensitivity of the test. ^10,11 ACE inhibitors should be withheld for 3 to 7 days before the study, depending on the half-life of the radiopharmaceutical to be used. In addition to ACE inhibitors, patients should also be questioned about new combination antihypertensive drugs, such as Teczem, which include both an ACE inhibitor (enalapril) and a calcium channel blocker (diltiazem).

Diuretics --A patient on chronic diuretics has an increased likelihood of volume depletion, which may reduce the specificity of the test; in addition, volume depletion increases the risk of a hypotensive response. Because of these concerns, it is advisable to stop diuretics for several days prior to the study.

Angiotensin II receptor antagonists --Angiotensin II receptor antagonists block type I angiotensin II receptors and have been used in place of ACE inhibitors to detect renovascular hypertension. ^12,13 Currently available angiotensin receptor blockers include losartan (Cozaar), irbesartan (Avapro), valsartan (Diovan), and candesartan (Atacand). The effect of chronic angiotensin II receptor blockade on the sensitivity and specificity of ACE inhibitor scintigraphy is not known. A baseline study cannot be performed if the patient is taking angiotensin II receptor antagonists. At present, it is appropriate to discontinue these drugs prior to ACE inhibition renography until further data become available.

Calcium channel blocker s--A recent report suggests that calcium channel blockers may result in a bilaterally symmetrical abnormal renogram curves in the absence of renal artery stenosis, ¹⁴ although we have not found calcium channel blockers to be a significant problem in our practice.

Which ACE inhibitor and what dose?

Captopril (25 to 50 mg crushed and administered orally with 250 mL of water) is the most widely used ACE inhibitor. A 25-mg tablet is sufficient unless the patient has delayed gastric emptying or poor absorption from the gastrointestinal tract. Food can interfere with the absorption of captopril, and patients should not eat before captopril scintigraphy. Since the peak activity of captopril does not occur until approximately 60 minutes after ingestion, the radiopharmaceutical should be given 1 hour after captopril.

A second approach is to inject enalaprilat (Vasotec, 40 µg/kg IV over 3 to 5 minutes, with a maximum dose of 2.5 mg), wait at least 15 minutes, and then inject the radiopharmaceutical. ^15-17 An advantage of enalaprilat is that the patient can be placed under constant observation for hypotension after enalaprilat injection as the technologist prepares for and then performs the study. Intravenous injection of enalaprilat also avoids the possibility of a false negative test due to poor absorption of captopril in a patient who has recently eaten or has delayed gastric emptying due to diabetes. A potential disadvantage of enalaprilat is that the patient may be at greater risk of a significant hypo tensive episode.

Monitoring blood pressure

Blood pressure must be monitored throughout the procedure. Volume depletion or asymptornatic hypotension secondary to ACE inhibition can result in bilateral symmetrical abnormalities in the renogram curves (figure 1). This phenomenon is uncommon, but may occur in as many as 3% of patients referred for ACE inhibition renography; it appears to be most likely to occur in patients who are volume- or salt-depleted. ¹⁸

One- versus a two-day protocol?

Some centers begin with captopril or enalaprilat renography because normal findings on ACE inhibitor renography obviate a baseline study. If the results are abnormal, the specificity can be improved by obtaining a baseline renogram; however, because of the administration of the ACE inhibitor, the patient will have to return for the baseline study on another day. In some centers, an abnormal ACE inhibition study in a patient with high clinical probability of renovascular hypertension is justification for angiography.

A second approach is to use a 1 to 2 mCi dose of MAG3 (Tc-99m mercaptoacetyltriglycine) or DTPA (Tc-99m diethylenetriaminepentaacetic acid) for the baseline study, administer the ACE inhibitor, and then obtain a second renogram with a significantly higher 8 to 10 mCi dose. This protocol consists of two studies on the same day and requires the patient to spend a longer time in the department, but the complete study is finished in a single day. The first approach is less costly if the time required for the patient to return on a second day for a baseline test is not factored into the calculation.

Quantitative measurements

We routinely measure a camera-based MAG3 clearance, post-void residual and several quantitative indices using the QuantEM ^TM software program which was initially developed at Emory for a GE platform ¹⁹ ; a more expanded version based on the multicenter trial was later developed for Elscint. ^20-22 Camera-based clearances are not as accurate as clearances based on plasma samples, but they appear to be highly reproducible in patients with stable renal function. ^23-26 In addition to measurement of a MAG3 clearance, the latest software version includes semi-automated assignment of kidney regions of interest, ²² automated assignment of background regions of interest, automated assignment of cortical regions of interest, and generation of the following quantitative indices which are useful in the diagnosis of renovascular hypertension.

Relative uptake-- The relative renal uptake of each radiopharmaceutical provides a measure of relative function and is an important parameter in the interpretation of most studies. The measurement is usually made during the 1 to 2, 1 to 2.5, or 2 to 3 minute period postinjection for MAG3, OIH, and DTPA. Background subtraction using a C-shaped, elliptical, or perirenal region of interest appears to be superior to no background or inferior background regions of interest ^2,27-29 and an automated background subtraction probably improves reproducibility. ²²

Time to peak height-- The time to the peak height on the renogram curve is a useful measurement in the evaluation of patients with suspected renovascular hypertension. In general, the peak should occur by 5 minutes after injection, but retention of the radiopharmaceutical in the renal calices or pelvis can alter the shape of the renogram and affect this measurement. ³⁰ The latest version of the QuantEM ^TM software automatically places cortical regions of interest and we routinely measure the time to peak and the 20 minute/maximum (min/max) ratios using cortical ROIs to minimize the effect of radiopharmaceutical retention in the calices or renal pelvis. ²⁴

The 20 or 30 minute/maximum ratios-- As renal function deteriorates, there is often a pronounced prolongation of the excretory phase of the renogram. The degree of abnormality can be quantitated by a measurement of residual cortical activity using the ratio of the counts at 20 or 30 minutes to the maximum (peak) counts. The 20 or 30 min/max ratio is also a useful index in the detection of renovascular hypertension. In a series of potential renal donors studied with MAG3, the 20 min/max ratio for background subtracted parenchymal regions of interest (activity within the collecting system was excluded from the ROI) was 0.18 ± 0.06. ³⁰ If the patient is not dehydrated and the 20 min/max ratio for the cortical ROI exceeds 0.36 (three standard deviations above the mean), the kidney is likely to be abnormal.

Dose infiltration-- If part of the dose is infiltrated, the excretory phase of the renogram curve may be prolonged ³¹ ; an increase in the grade of the renogram curve from 0 to 2 or 1 to 2 grades (figure 1) can lead to an erroneous interpretation of an ACE inhibition renogram. A 30-second injection site image at the conclusion of imaging is routine in our institution; the QuantEM ^TM software estimates what percent, if any, of the injected dose was infiltrated. Infiltration can also be evaluated qualitatively by viewing an image of the injection site.

Diagnostic criteria

MAG3 and OIH-- With MAG3 and OIH, the most specific diagnostic criterion for renovascular hypertension is a ACE inhibition induced change in the renogram (figure 2). A change in the relative uptake of MAG3 or OIH by 10 percentage points (50/50 to 40/60) is uncommon even in a patient with RVH, but it is highly significant when it occurs. For MAG3 and OIH, the most important criterion is parenchymal retention in the affected kidney(s). ^2,32 Parenchymal retention is secondary to the decrease in the glomerular filtration rate (GFR) induced by ACE inhibition; with the decrease in GFR, there is decreased flow in the renal tubules and delayed washout of the radionuclide from the tubules and tubular lumen. ³³ We prefer renograms derived from the cortical ROIs because they help avoid the diagnostic difficulty that can be introduced by retention of the tracer in the collecting system. Parenchymal retention may be evaluated qualitatively by changes in the shape of the renogram curve (figure 3) or it may be evaluated quantitatively by a prolongation of the 20 or 30 min/max ratio and/or a prolongation of the time to peak. An increase in the 20 min/max ratio of 0.15 or greater for parenchymal ROIs represents the 90% confidence limit for a significant change. ^2,9 A prolongation of the time to peak of 120 seconds for a cortical ROI is significant at the 90% to 95% confidence limit. It is important to note, however, that a change from 5 to 7 minutes is more meaningful than a change from 15 to 17 minutes.

DTPA-- The principal diagnostic criterion for the purely glomerular agent DTPA is a decrease in uptake by the affected kidney(s) resulting in a change in the relative uptake in patients with unilateral disease or asymmetrical bilateral disease. The decrease in DTPA uptake following ACE inhibition is due to a decrease in glomerular filtration of the affected kidney.

A reduction in the relative uptake greater than 10 percentage points (50/50 to 60/40) is a highly significant change and 5 to 9 percentage points is considered to be a intermediate response, ^2,34,35 although a recent study performed under carefully controlled conditions suggests that smaller changes in relative uptake may be significant. ⁹ Parenchymal retention with a change in the shape of the renogram curve following ACE inhibition is also an important diagnostic finding. As with MAG3 and OIH, parenchymal retention can be quantitated by a delay in the time to peak or an increase in the 20 to 30 min/max ratios although, in general, changes have to be much more pronounced than with MAG3 and OIH to be significant. ^2,9,35

Reporting the test results

The Consensus Panel has recommended that the test results be reported as high, intermediate, or low probability for RVH. Most studies have reported sensitivities and specificities in the range of 80% to 90%, although the gold standard has often been the detection of renal artery stenosis in a hypertensive patient, not the blood pressure response to revascularization. Almost uniformly, better results are obtained when the end point is normalization or reduction in blood pressure following revascularization. ^2,34,36-41 In communicating with the referring physician, it is important to distinguish between the hypertensive patient with normal renal function and the hypertensive patient with ischemic nephropathy. The utility of the test differs substantially in these two patient populations.

ACE inhibition renography in patients with normal function

ACE inhibitor renography is highly accurate in patients with normal renal function (normal creatinine and the absence of a small, poorly functioning kidney); the sensitivity and specificity of ACE inhibitor renography for renovascular hypertension in this patient population approach 90%.

ACE inhibitor renography in patients with ischemic nephropathy

A positive ACE inhibition test result indicates that hypertension is very likely to improve following revascularization; however, it is important to recognize that patients with azotemia or a small, poorly functioning kidney often have an intermediate probability test result (abnormal baseline study which does not change following ACE inhibition). In the appropriate clinical setting, an intermediate test result may be sufficient to refer a patient for angiography. When there is a high index of suspicion, azotemic patients may be referred directly for angiography. MR angiography may play an increasing role in this patient population.

Patients with ischemic nephropathy may or may not have co-existing renovascular hypertension; however, revascularization is sometimes performed in these patients in an attempt to improve or stabilize renal function. Revascularization can result in an amelioration or stabilization of azotemia, but a reduction in complications or an improvement in survival compared to currently available medical therapy has not yet been demonstrated and the long-term utility of this approach is still being debated. ^6,9,42-44

Conclusion

If a patient has a moderate to high likelihood of RVH and normal renal function, ACE inhibition renography provides a logical, noninvasive, and cost-effective approach to patient management. A normal ACE inhibition renogram obviates the need for further work-up; an abnormal study should lead to referral for angiography and revascularization. If a small, poorly functioning kidney is identified, angiography or Duplex sonography, depending on local experience and expertise, is a reasonable next step.

The evaluation of a patient with azotemia is more problematic. A positive test result should lead to angiography and revascularization if technically feasible, but these patients have a high percentage of intermediate probability test results. A large percentage of intermediate test results is not necessarily a problem if the referring physician understands the likelihood of this outcome when referring such a patient for ACE inhibition renography. An intermediate test result in the appropriate clinical setting may be sufficient to refer a patient for angiography. False negative results are uncommon but when they occur, they appear to be more likely in azotemic patients with bilateral disease, probably due to pressure natriuresis with suppression of the renin angiotensin system. AR

References

1. Holley KE, Hunt JC, Brown AL Jr., et al: Renal artery stenosis: A clinical pathologic study in normotensive and hypertensive patients. Am J Med 37:14-22, 1964.

2. Taylor A, Nally J, Aurell M, et al: Consensus report on ACE inhibitor renography for detecting renovascular hypertension. J Nucl Med 37:176-182, 1996.

3. Prigent A: The diagnosis of renovascular hypertension: The role of captopril renal scintigraphy and related issues. Eur J Nucl Med 20:625-644, 1993.

4. 1999 Consensus Committee. Procedure guideline for ACE inhibitor renography. Available for download at http://www.snm.org.

5. Taylor A: Radionuclide renography: A personal approach. Sem Nucl Med 29:102-127, 1999.

6. Blaufox MD, Middleton ML, Bongiovanni J, Davis B: Cost efficacy of the diagnosis and therapy of renovascular hypertension. J Nucl Med 37:171-177, 1996.

7. Bernini G, Pinto S, Arzilli F, et al: Treatment of renovascular disease and of renovascular hypertension. J Nephrology 11:311-317, 1998.

8. Sfakianakis GM, Bourgoignie JJ, Georgiou M, et al: Diagnosis of renovascular hypertension with ACE inhibition scintigraphy. Radiol Clin North Am 31:831-848, 1993.

9. Blaufox MD, Fine EJ, Heller S, et al: Prospective study of simultaneous orthoiodohipurate and diethylenetriaminepentaacetic acid captopril renography. J Nucl Med 39:522-528, 1998.

10. Setaro JF, Saddler MC, Chen CC, et al: Simplified captopril renography in diagnosis and treatment of renal artery stenosis. Hypertension 18:289-298, 1991.

11. Visscher CA, de Zeeuw D, Huisman RM: Effect of chronic ACE inhibition on the diagnostic value of renography for renovascular hypertension: A preliminary report. Nephrol Dial Transplant 10:263-265, 1995.

12. Liepe K, Seemann A, Gross P, et al: Comparison of losartan and captoril in the diagnosis of renovascular hypertension. Eur J Nucl Med 24:9410, 1997.

13. Fuster D, Marco MP, Setoain FJ, et al: A case of renal artery stenosis after transplantation: Can losartan be more accurate than captopril renograhy? Clin Nucl Med 23:731-734, 1998.

14. Claveau-Tremblay R, Turpin S, Debraekeler M, et al: False-positive captopril renography in patients taking calcium antagonists. J Nucl Med 39:1621-1626, 1998.

15. Erbsloh-Moller B, Dumas A, Roth D, et al: Furosemide I-131 hipppuran renography after angiotensin-converting enzyme inhibition for the diagnosis of renovascular hypertension. Am J Med 90:23-29, 1991.

16. Kopecky RT, McAfee JG, Thomas FD, et al: Enalaprilat-enhanced renography in a rat model of renovascular hypertension. J Nucl Med 31:501-507, 1990.

17. Black HR, Bourgoignie JJ, Pickering T, et al: Report of the working party group for patient selection and preparation. Am J Hypertens 4:745S-456S, 1991.

18. Fanti S, Dondi M, Guidalotti PL, et al: Bilateral symmetrical induced changes in captopril scintigraphy. J Nucl Med 39:86P, 1998.

19. Taylor A, Corrigan PL, Galt J, et al: Measuring technetium-99m-MAG3 clearance with an improved camera-based method. J Nucl Med 36:1689-1695, 1995.

20. Taylor A, Manatunga A, Morton K, et al:
Multicenter trial validation of a camera based method to measure Tc-99rn mercaptoacetyltriglycine, or Tc-99m MAG3, clearance. Radiology 204:47-54, 1997.

21. Bocher M, Shrem Y, Tappiser A, et al: Technetium-99m-MAG3 clearance: Comparison of camera based methods. Submitted for publication.

22. Halkar RK, Shrem Y, Galt Jr., et al: Interoperator variability in quantitating the MAG3 renal uptake based on semiautomated and manual regions of interest. J Nucl Med 37:293P, 1996.

23. Chachati A, Meyers A, Godon JP, Rigo P: Rapid method for the measurement of differential renal function: Validation. J Nucl Med 28:829-836, 1987.

24. Klingensmith WC, Briggss DE, Smith WI: Technetium-99m-MAG3 renal studies: normal range and reproducibility of physiologic parameters as a function of age and sex. J Nucl Med 35:1612-1617, 1994.

25. Russell CD, Dubovsky EV: Single-sample Tc-99m MAG3 renal clearance in the long-term management of patients with spinal cord injury. Nucl Med Comm 19:494, 1998.

26. Taylor A, Myrick S, Grant S, et al: A prospective study to compare the reproducibility of camera based MAG3 and creatinine clearance measurements. J Nucl Med 40:52P, 1999.

27. Prigent A, Cosgriff P, Gates GF, et al: Consensus report on quality control of quantitative measurements of renal function obtained from renogram. Sem Nucl Med 1999.

28. Peters AM, George P, Ballardie F, et al: Appropriate selection of background for 99mTc-DTPA. Nucl Med Commun 9:973-985, 1988.

29. Taylor A, Thakore K, Folks R, et al: Background subtraction in Tc-99m-MAG3 renography. J Nucl Med 35:2054-2055, 1994.

30. El-Galley R, Clarke HS, O'Brien DP, Taylor A: Normal parameters for Tc-99m MAG3 renography. J Nucl Med 39:87P, 1998.

31. Slavin JD, Jung WK, Spencer RP: False-positive study with Tc-99m DTPA caused by infiltration of dose. Clin Nucl Med 21:978-980, 1996.

32. Fommei E, Mezzasalma L, et al: Detection of renovascular hypertension by captopril renography with MAG3: A multicentre study. Eur J Nucl Med 24:941, 1997.

33. Visscher CA, de Zeeuw D, de Jong PE, et al: Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension. J Nuct Med 37:482-488, 1996.

34. Fornmei E, Ghione S, Hilson AJW, et al: Captopril radionuclide test in renovascular hypertension: A European multicentre study. Eur J Nucl Med 20:625-644, 1993.

35. Dey HM, Hoffer PB, Lerner E, et al: Quantitative analysis of the technetium-99m-DTPA captopril renogram: Contribution of washout parameters to the diagnosis of renal artery stenosis. J Nucl Med 34:1416-1419, 1993.

36. Kahn D, Ben-Haim S, Bushnell DL, et al: Captopril-enhanced Tc-99m MAG3 renal scintigraphy in subjects with suspected renovascular hypertension. Nuclear Medicine Comm 15:515-528, 1994.

37. Mittal BR, Kumar P, Arora P, et al: Role of captopril renography in the diagnosis of renovascular hypertension. Am J Kidney Dis 28:209-213, 1996.

38. Dondi M, Fanti S, De Fabritiis A, et al: Prognostic value of captopril renal scintigraphy in renovascular hypertension. J Nucl Med 33:2040-2044, 1992.

39. Fornmei E, Ghione S, Hilson AJW, et al: Captopril radionuclide test in renovascular hypertension: European multicenter study. In: O'Reilly PH, Taylor A, Nally JV, (eds): Radionuclides in Nephrourology, vol 1. Blue Bell, PA, Field and Wood, 1994.

40. Setaro JJF, Saddler MC, Chen CC, et al: Simplified captopril renography in diagnosis and treatment of renal artery stenosis. J Hypertens 18:289-298, 1991.

41. Geyskes GG, deBruyn AJG: Captopril renography and the effect of percutaneous transluminal angioplasty on blood pressure in 94 patients with renal artery stenosis. Am J Hypertens 4:685S-689S, 1991.

42. Wilcox CS: Ischemic nephropathy: Noninvasive testing. Sem Nephrol 16:43-52, 1996.

43. Soulen MC: Renal angioplasty: Underutilized or overvalued? Radiology 193:19-21, 1994.

44. Derkx FHM, van Jaarsveld BC, Drijnen P, et al: Renal artery stenosis toward the year 2000. J Hypertens 14:5167-5172, 1996.

45. Taylor A Jr., Nally JV: Clinical applications of renal scintigraphy. AJR 164:31-41, 1995.