Applied Radiology

Hypertension is one of the most common medical problems in the world today. Renovascular factors are a major cause of potentially curable hypertension. Better noninvasive screening procedures for identification of renovascular hypertensive patients are needed. This article reviews the pathophysiology of renal artery stenosis, the effects and pharmacology of angiotensin-converting enzyme (ACE) inhibitors, the use of enalaprilat (Vasotec) in conjunction with renal scintigraphy, and the patient selection criteria. Vasotec is an effective, practical, and safe ACE inhibitor used to augment the renogram study in screening patients for suspected renovascular hypertension. For ACE inhibitor renograms to be cost-effective in screening patients for suspected renovascular hypertension, strict adherence to the guidelines of patient selection must be imposed by referring physicians to ensure a prevalence rate of greater than 30% in the screened

patient population.

Hypertension is one of the most common medical problems in the world today. It affects nearly 60 million people in the United States alone.1 Hypertensive cardiovascular disease is one of the leading causes of death in the United States. Renovascular factors remain a major cause of potentially curable hypertension, but renovascular hypertension only may affect less than 1% of the general population.2 With the advances in percutaneous transluminal renal angioplasty (PTRA) and other surgical techniques, there is profound interest in developing better noninvasive screening procedures for the identification of patients with potentially correctable causes of hypertension.3,4

Angiotensin-converting enzyme (ACE) inhibition used in conjunction with renal radionuclide studies have been cited as a good noninvasive study for the detection of significant renal artery stenosis.5-12 Captopril (Capoten®) has been the traditional ACE inhibitor used in the various study groups published.10,11,13-16 There have been very few, if any, other ACE inhibitors studied in conjunction with renal scintigraphy. The observed sensitivity and specificity of several prospective studies using captopril average 75% to 95% and 80% to 93%, respectively.5,10,11,14,17-21 There are no published data using other ACE inhibitors.

This article reviews the alterations in renal physiology in patients with renal artery stenosis (RAS), the effects of ACE inhibition, and the use of enalaprilat (Vasotec®) in conjunction with renal scintigraphy in the evaluation of patients with possible renal artery stenosis, as well as patient selection criteria.

Pathophysiology of renal artery stenosis and the effects ofACE inhibition

Constriction of the renal artery leads to a cascade of important hemodynamic and humoral responses within the affected kidney. Initially, there is an attempt to maintain blood flow by vasodilatation distal to the stenotic site. With significant stenosis, there is a decrease in distal renal artery pressure and blood flow, leading to decreased renal perfusion pressure. When this occurs, renin is released by the juxtaglomerular apparatus and augments intrarenal angiotensin II production.

Within the affected kidney, the angiotensin II-dependent renal vasoconstriction attenuates the fall in renal blood flow and affects the glomerular filtration rate (GFR) by controlling the vascular tone of the efferent renal arterioles. Angiotensin II preferentially causes vasoconstriction of the efferent arterioles to maintain transcapillary pressures within the glomerulus that maintains the GFR of the affected kidney.22-27

However, in the presence of ACE inhibition, which blocks the formation of angiotensin II, there would be a significant reduction in the postglomerular efferent resistance and a decrease in the GFR of the stenotic kidney. This decrease in individual renal function

is assessed accurately and noninvasively using conventional renal radionuclide studies.11,28

Other systemic effects of angiotensin II include the stimulation of secretion and synthesis of aldosterone, antidiuretic hormone (ADH), adrenocorticotropin (ACTH), epinephrine, and norepinephrine. It causes generalized vasopressor effect on the smooth muscle cells of the arterioles throughout the cardiovascular system, leading to the elevation of systemic mean arterial pressure. These effects likewise are suppressed by ACE inhibitors.

Pharmacology of ACE inhibitors

As noted above, a reduction in renal perfusion pressure results in preferential angiotensin II mediated vasoconstriction of the efferent arterioles in an attempt to maintain the GFR of the stenotic kidney. ACE inhibitors block the formation of angiotensin II, thereby interfering with the renin-angiotensin-aldosterone system. This reduces the postglomerular efferent resistance, decreasing the GFR of the stenotic kidney, renal blood flow, and systemic blood pressure. It also inhibits the degradation of bradykinin. Captopril (Capoten) is one of the widely used oral ACE inhibitors on the market today. It also has been used and studied in conjunction with renography in the evaluation of patients with possible renovascular hypertension.10,11,13-16 Captopril is given orally at a dose of 25 mg to 50 mg. Rapid absorption occurs with peak blood levels at about one hour. Reduction of blood pressure is maximal at 60 to 90 minutes after oral administration of an individual dose. The duration of effect is dose-related.

Enalaprilat (Vasotec) is also one of the widely used ACE inhibitors available in oral and parenteral forms. Its parenteral form, in its active form, has made it convenient to administer the medication at a standard dose without having to rely on the patient's absorption kinetics to obtain a significant serum level.

In its active form, it is administered at a dose of 0.04 mg/kg up to a maximum of 2.5 mg. Vasotec results in the reduction of both supine and standing systolic and diastolic blood pressure, usually with no orthostatic component, within 15 minutes after the administration of an individual dose. The duration of effects also is dose-related. The earlier onset

of action of Vasotec significantly shortens the duration of the post-Vasotec examination.

Patient selection criteria Blaufox et al have suggested that screening for renovascular hypertension is not cost-effective at a prevalence rate of less than 30%.29 To ensure that the prevalence rate is greater than 30%, patients must possess certain characteristics, which were established by the Working Party Group for Patient Selection and Preparation during the Captopril Renogram Consensus Conference.30,31 These characteristics include the following.

1. Well-documented, recent-onset hypertension, especially if the diastolic blood pressure is greater than or equal to 105 mm Hg.

2. Known long-standing and well-controlled hypertension that becomes refractory to an existing regimen when there is no other explanation for the resistance to treatment.

3. Clinical evidence of generalized vascular disease (i.e., peripheral vascular disease, cerebrovascular disease).

4. Hypertension and abdominal bruits.

5. Hypertension and an elevated

serum creatinine when no other etiology can be found to explain the renal

dysfunction.

6. Patients under the age of 25 who develop moderate or severe hypertension (i.e., diastolic blood pressure of greater than or equal to 105 mm Hg), especially if they are white and not obese.

7. Refractory hypertension on an adequate three-drug antihypertensive regimen when no other etiology can

be found.

8. Hypertension associated with new or more severe renal failure when treated with ACE inhibitors.

Other types of patients in whom ACE inhibitor renography may be of help, according to the Report of the Working Party Group for Patient Selection and Preparation, include the following.

1. Significant renal insufficiency without hypertension when no other etiology for the impaired renal function may be found.

2. Hypertension after a renal transplant.

3. Mild renal insufficiency with or without significant hypertension, with vascular disease elsewhere.

4. New or more severe renal failure while on ACE inhibitors.

Methodology

At Loyola University Medical Center, we routinely obtain a medication history. If the patients are on any ACE inhibitors, the referring physicians are requested to withhold ACE inhibitors for at least 72 hours prior to the day of the examination. Other forms of antihypertensive medications may be prescribed for the patients.

One hour prior to the initial baseline study, the patients are asked to take in 10 cc/kg of water orally. Patients should void immediately prior to the study. Images are obtained with a large field of view gamma camera equipped with a low-energy all-purpose collimator. The system is peaked at 140 keV with a 20% window.

With the patient supine and the camera positioned posteriorly, 5 mCi of Tc-99m MAG-3 (Mallinckrodt) is injected intravenously. Analog images are acquired dynamically at 180 seconds per frame for 7 frames (21 minutes). Dynamic computer acquisition is done at 15 seconds per frame, 84 frames, in a 64 x 64 word matrix.

Four hours later, an IV line of 0.9% NaCl solution at K/O is inserted. The patients were then attached to a blood pressure monitor and readings were obtained every 5 minutes for 30 minutes and every 15 minutes for the rest for the duration of the patients' stay in the department.

After obtaining a baseline blood pressure reading, enalaprilat (Vasotec) at a dose of 0.04 mg/kg is administered IV to a maximum of 2.5 mg over 5 minutes. The patients are observed for 10 to 15 minutes before a repeat Tc-99m MAG-3 renogram is performed with the same dose and technique as the baseline study. The IV line remains in place until the completion of the study.

Interpretation

The studies are categorized as normal or abnormal renograms with no evidence of unilateral renal artery stenosis, and abnormal study with evidence of renal artery stenosis. Normal studies were described as those having normal baseline renograms with no significant difference in the post-Vasotec renogram. Abnormal renograms with no evidence of unilateral renal artery stenosis were described as having abnormal baseline renograms that do not show any significant difference post Vasotec.

An abnormal study with evidence of renal artery stenosis shows a significant difference in renal function between the baseline and the post-Vasotec reno-

grams. The post-Vasotec study shows a delay in the time to peak activity and/or an impairment in the excretory (third) phase of the renogram of the affected kidney.27,32-35

Demonstrative cases

Case 1-A 64-year-old hispanic female was referred for Vasotec renal scan because of uncontrolled hypertension. The patient has been hypertensive for the past year and has been on multiple antihypertensive medications. Presently, the patient is on amlodepine (Norvasc®). Baseline blood pressure at the time of the study was 168/74. Fifteen minutes after the IV administration of Vasotec, the blood pressure decreased to 130/72. At the end of the study, the blood pressure was 126/80. At no time during the study did the patient complain of any hypotensive symptoms. The renogram curves (figure 1) of the patient, pre- and post-Vasotec, are normal.

Case 2-A 74-year-old black male was referred for a Vasotec renal scan because of hypertension. The patient has been a known hypertensive for the past five years and has been on diuretics and calcium channel blockers. The patient's blood pressure recently became difficult to control with his usual medications. His baseline blood pressure was 192/108. At 15 minutes post Vasotec administration, the blood pressure was 132/68. At the end of the study, his blood pressure was 112/67.

The patient was asymptomatic and did not manifest any signs of hypotension. The pre- and post-Vasotec renogram curves (figure 2) show a significant alteration in renal function of the left kidney in the post-Vasotec study when compared with the baseline study. The patient eventually had a renal angioplasty and his hypertension improved significantly.

Conclusion

Based on the captopril data, ACE inhibitor renography is safe and effective. Vasotec offers the advantage of IV administration with rapid predictable effects. Although Vasotec renal scintigraphy is a good noninvasive screening procedure, strict adherence to the guidelines of patient selection needs to be imposed by referring physicians so as to ensure a prevalence rate of greater than 30% in the screened patients for renovascular hypertension; this is so that the test is cost-effective for screening patients for possible renal artery stenosis. AR

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Suggested readings

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