Management of the patient with renovascular hypertension

Management of the patient with renovascular hypertension

Fundamentals of clinical cardiology I I , Management of the patient with renovascular hypertension Stephen P' Youngberg, M.D.* Sheldon G. Sheps, M...

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Fundamentals of clinical cardiology I

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Management of the patient with renovascular hypertension Stephen P' Youngberg, M.D.* Sheldon G. Sheps, M.D. Cameron G. Strong, M.D. Rochester, Minn.

Information from clinical and experimental investigations during the past two decades allows the clinician to pursue a more rational approach to the diagnosis and management of the patient with hypertension resulting from renovascular disease. Methods of detecting these lesions have been established. In particular, aortorenal angi0graphy and the determination of renal venous renin activity levels under controlled conditions have contributed materially to the favorable results after renovascular surgery in the selected patient. However, the clinical use of newer, more potent medications t h a t inhibit renin release or otherwise interfere with the renin-angiotensin-aldosterone hormonal system offers great potential in medical therapy. Patients with renovascular hypertension, the most common cause of secondary arterial hypertension, are not a homogeneous group. The estimated 5 per cent of the hypertensive population that have renal artery stenosis as the underlying cause of elevated blood pressure is largely comprised of two groups of patients: those with atherosclerotic disease and those with the nonatherosclerotic fibrous and fibromuscular stenoses. Thus, the type, location, and severity of renal and renovascular lesions, as well as associated disease processes, are most important in determining the management of such patients. 1 From the Divisions of Nephrology and Internal Medicine. and Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn. Received for publication.Dec. 30. 1976. Reprint requests: Dr. S. P. Youngberg, c/o Section of Publications. Mayo Clinic. 200 First St. S.W., Rochester', MN 55901. *Dr. Youngberg is the recipient of a postdoctoral fellowship from the National Kidney Foundation.

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Pathologic features Atherosclerotic renovascular disease. Atherosclerotic plaques may compromise the ostium Of one or both renal arteries, or Such atheromatous plaques may be located in the renal artery itself, usually in the proximal third of the vessel (Fig. 1). In either instance, the disease process may progress, ultimately causing complete occlusion of the involved vessel. Both renal arteries generally are involved. Multiple areas of atherosclerotic narrowing are not uncommon. In a high percentage of patients with atherosclerotic stenoses; as well as in those with fibromuscular disease, fusiform poststenotic dilatation of the renal artery is observed, and on rare occasions, the dilatation may be such t h a t angiographically and pathologically it resembles an aneurysm of the renal artery. Because atherosclerotic lesions of the renal artery are generally local manifestations of widespread atherosclerosis, atheromatous disease frequently will be observed in the aorta and elsewhere.: Fibromuscular disease. Recently, Harrison and McCormack '3 classified nonatherosclerotic stenoses on the basis of the arterial l a y e r - i n t i m a , media, or adventitia-in which the leSions predominateand on whether there is fibroplasia, hyperplasia, dissection, or aneurysm formation (Fig. 2). Medial dissection (5 per cent of patients) usually is clearly distinguishable on the renal arteriogram. Medial fibroplasia (60 to 70 per cent of Patients) and the rare medial hyperplasia (less than 5 per cent) generally are seen as multifocal stenoses in which there are large aneurysms or !'beads" t h a t exceed the expected diameter of the renal artery because of extensive mural thinning

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Focal

~j Atherosclerosls

Fibromuscular changes have been found in most arteries, in addition to the r e n a l artery, notably the carotid arteries, where they may cause symptomatic stenoses. Additionally, some investigations have found an associated high incidence of intracranial berry aneurysms in patients with fibromuscular renal artery disease. 4'

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Fig. 1. Schematicrepresentation of type and location of renal artery occlusivedisease. Lesion predo minorltly

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Fig. 2. Types of idiopathicfibrous and fibromuscularstenosis of the renal artery. (From Harrison, E. G., Jr., and McCormack, L. J.: Pathologicclassificationof renal arterial disease in renovascularhypertension,Mayo Clin.Proc. 46:161, 1971. Ni~producedwith permission.) between thickened fibromuscular ridges. Perimedial fibroplasia (15 to 20 per cent of patients) is characterized by a generalized but irregular ~hickening Of the outer media which may simulate multifocal stenosis a n d beading, b u t the diameter of the "beads" is less than t h a t of the uninvolved renal artery. The intimal and adventitial lesions are rare (1 to 2 per c e n t ) a n d generally are focal or tubular stenoses. In contrast to atheromatous disease, fibromuscular stenoses characteristically involve the distal portion of the r e n a l artery and its branches {Fig. 1).

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Systemic hypertension is the physiologic consequence of stenosis of the renal artery {arteries) in the patient with renal artery disease. A number of concepts in the pathophysiology of renovascular hypertension have evolved during the past several years from the pioneering work of Goldblatt 6 in experimental hypertension. Experimentally, there are two forms of renovascular hypertension. In the first, a renal artery is constricted, reducing the blood flow to that kidney and causing ischemia. The contralateral kidney is left untouched. In the second form, a renal artery is constricted, but the opposite kidney is removed. Hence, these models of renovascular hypertension are termed one-clip twokidney Goldblatt hypertension and one-clip onekidney Goldblatt hypertension, respectively. Both animal models become hypertensive to a similar degree, but important differences exist in the pathophysiologic mechanisms. The renin-angiotensin-aldosterone hormonal system has been established as an integrated capacity-volume system of major importance in the control of arterial blood pressure2 In the oneclip one-kidney experimental model, the plasma reninactivity level may be normal or reduced and the renin content in the kidney reduced. However, in the one-clip two-kidney hypertension model, there are increased or, in the presence of hypertension, inappropriately high plasma renin activity levels, increased renal renin content in the ischemic kidney (on the side of renal artery constriction), and a reduced renin content in the contralateral kidney. The role of renin, and therefore, of its physiologic consequence-vasoconstrict i o n - h a s been further investigated by the use of special tools: antirenin serum, antibodies to angiotensin II, and specific peptide inhibitors of angiotensin II. Administration of these agents lowers the blood pressure in the one-clip two-kidney hypertension model but not in the one-clip one-kidney hypertensive animalsP' ' However, if the latter group is

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Management of renovascular hypertension first prepared by sodium depletion, the above maneuvers lower the blood pressure in this group as well. TM Th e effect of sodium depletion in lowering blood pressure in the one-clip onekidney model, while not affecting the one-clip two-kidney form, was first demonstrated by Swales and colleagues. 1l Consequently, these two experimental models of renovascular hypertension may be viewed as renin-dependent or vasoconstriction-mediated in one-clip two-kidney hypertension and as sodium- or volume-dependent in one-clip one-kidney hypertension. 12 Retention of salt and water by the ischemic kidney in the one-clip one-kidney model causes volume expansion and hypertension and results in suppression of the renin-dependent vasoconstriction manifested in the one-clip two-kidney model. However, their common basis is unmasked by sodium restriction, whereby the volume-dependent form is converted to a vasoconstriction renin-dependent form. Current research emphasizes the possibility of a role for depressor substances in the development of hypertension. Further investigation into the role of prostaglandins 2~' TM and kinins '~ m ay disclose important interactions with pressor systems such as the renin-angiotensin-aldosterone hormonal system, which already has been shown to have a central role. Th e mechanisms proposed for these experimental models occur in human renovascular hypertensive disease, and the understanding of these principles provides a basis for the diagnostic evaluation and selection of therapy for these patients. TM Clinical characteristics

The review of the clinical characteristics of patients with documented renovascular hypertension by Simon and associates" for the Cooperative Study of Renovascular Hypertension examined in detail the thesis t h a t hypertension associated with unilateral renal disease, curable by surgery, had distinctive characteristics. The task of the clinician in differentiating the patient with renovascular hypertension from the large pool of patients with essential hypertension is difficult because no one characteristic or combination of characteristics is diagnostic. Of the many characteristics t hat have been suggested, a few have become important markers for renovascular hypertension. Patients with renovascular

American Heart Journal

Table I. Urographic signs suggesting renovascular disease in hypertensive patients 1. Decreasedrenal size-disparity in renal pole-to-polediameter of > 1.5 cm. 2. Unilateral delay in appearance time of the contrast medium in the pelvic calyceal collecting system of the involved or more severely involved kidney in the early films 3. Late hyperconcentrationof contrast medium 4. Ureteral notching suggesting the presence of pelvic-ureteral collateral vessels 5. Delayedwashout of pelvic calyceal contrast medium with diuresis 6. Nonfunctioningkidney on excretoryurogram, with normal retrograde pyelogram 7. Defect in renal silhouette suggestive of segmental renal infarction

hypertension are not a homogeneous group; patients with fibromuscular disease as a group differ in m any characteristics from those patients with atherosclerotic renal artery disease. ~7" TM Generally, the group with hypertension secondary to fibromuscular disease is younger, has more females than males, is more likely to have no family history of hypertension, and is less likely to have target-organ damage (heart, central nervous system, kidneys) t han is the group with essential hypertension or atherosclerotic renovascular disease. In the former group, upper quadrant abdominal or flank bruits of systolic-diastolic or continuous nature are common, being heard in as many as 70 per cent of patients with fibromuscular disease. Because of multivessel involvement in this disease, a search should b e made for other vascular bruits. The isolated abdominal bruit t h a t is only heard in systole is not correlated with the presence of a stenotic renal vessel. Funduscopic examination commonly reveals less severe retinal artery changes-changes limited to narrowing and focal constriction (angiospastic) or retinal arteriosclerosis without exudates or papilledema, t h a t is Groups 1 and 2 of the Keith-Wagener-Barker classification. In contrast, patients with renovascular hypertension due to atherosclerosis are older and frequently have a family history of hypertension or its sequelae. Often, they have severe retinopathy and target-organ damage. Most of the patients with atherosclerotic renovascular hypertension are males.

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Patients with atherosclerotic renal artery disease frequently have considerable systemic vascular disease at the outset. Those with more severe renal artery involvement have a much higher incidence of symptomatic coronary, cerebrovascular, abdominal aortic, and peripheral vascular disease, which often may necessitate surgical management. Additional symptomatic cardiovascular complications develop in a significant number of these patients as time passes. ~

Diagnostic investigations A lack of agreement exists in regard to the extent of diagnostic evaluation of the hypertensive patient which is needed to distinguish essential hypertension from secondary causes. The history and physical examination often provide a basis for adequate suspicion. In general, the more severe the hypertension, the more frequent and severe the symptoms. In any patient with severe hypertension, a renovascular cause should be considered. During the general examination, in addition to undergoing the routine laboratory tests, the hypertensive patient should have a urinalysis, determination of serum electrolytes, and determination of serum creatinine level as a measure of renal function before therapy is begun. If the initial clinical assessment suggests t h a t the hypertension is secondary or is moderate or severe or of recent onset {especially in the young patient who is likely to require long-term antihypertensive therapy), further diagnostic investigations should be carried out. Rapid-sequence excretory urography can provide useful anatomic-physiologic information in the search for renovascular causes of hypertension. The cardinal manifestations of renovascular disease, as displayed urographically, are listed in Table I. In the Cooperative Study of Renovascular Hypertension, 11.4 per cent of 771 essential hypertensive patients had one of these signs, while 83 per cent of patients with significant stenosis had one or more abnormalities. The urographic findings were normal in 16.7 per cent of patients with angiographically demonstrated stenoses. Perhaps the most discriminatory urographic feature is t h a t of either a diminished early nephrogram phase or a delayed appearance time on the involved side; 59 per cent of patients with significant stenoses had this sign, but only 2 per cent of those with essential hypertension did. 19, ~0

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In our experience, urographic abnormalities occur in approximately 70 per cent of patients with hypertension and severe renal artery stenosis. The incidence is approximately 50 per cent in patients with moderate stenosis. A difference in pole-to-pole diameter of the two kidneys of 1.5 cm. or more occurs in approximately 60 per cent of patients with severe renal artery stenosis. Of patients without such a difference in renal mass, approximately 10 per cent have one or more of the other features. Notching of the ureters (so-called scalloping} by large collateral arteries is observed rarely, and almost invariably when this is seen, the underlying disease is fibromuscular dysplasia. In the further evaluation of the hypertensive patient, the radioisotope renogram can assess the separate function of the kidneys. 18,~1 When patients are studied in the supine position and in the moderately hydrated state, a good qualitative correlation is found between the findings on an isotope renogram and the renal plasma flow, as determined by separated renal clearances of paminohippurate. Renographic abnormalities may not always indicate renal artery disease because such abnormalities may be due to other renal disease or anatomic variations. Thus, the renogram should be considered a renal function test and not a screening procedure for renovascular disease. It is best utilized in conjunction with the information obtained from excretory urography and clearance measurements. In the individual patient, the renogram can be a most useful qualitative test of the function of the separate kidneys, both in the initial and follow-up evaluations, particularly after corrective renal artery surgery. Renal arteriography has evolved over the past 20 years to have a major role both in the diagnosis of renovascular disease and in the selection of candidates for surgical procedures. Current techniques, in which multiple projections, selective renal artery injections, and magnification techniques are used, provide accurate anatomic evidence for the detection or exclusion of renal artery obstructive disease. ~ In the past, the only procedure for assessing the significance and correctability of a renovascular lesion was that of separated renal function studies. ~3 These tests, based on demonstrating excessive sodium and water reabsorption by the affected kidney, are technically complex, requir-

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ing the urologist to place occlusive ureteral catheters and to use sophisticated laboratory support for the determination of standard renal clearances. However, this technique is a reliable tool in determining surgical correctability, and it remains in use in conjunction with measurements of renal pressor substances in some centers. 24 The assessment of the functional significance of a renovascular lesion in causing high blood pressure involves the measurement of r e n a l pressor substances. The proper determination of plasma renin activity in the individual renal veins and inferior vena cava is a highly reliable indicator of potential surgical relief of hypertension. ~ An important prerequisite for these studies is the avoidance of pharmacologic agents that may alter the renin-angiotensin-aldosterone system, such as the commonly used cyclic progestational agents or estrogens, diuretics, propranolol, methyldopa, clonidine, catecholamine-depleting agents, and hydralazine. Particularly to be avoided are agents such as propranolol and methyldopa, which interfere with renin release. Our present regimen is to stop the use of antihypertensive medications for 4 weeks before determination of renin activity (except for guanethidine, which may be used as needed to control severe hypertension2~), to replete body potassium stores, and to maintain the patient on a normal sodium diet (approximately 135 mEq./day). The patient then is placed on a program to effect acute sodium depletion, utilizing a diet of 20 mEq. Na, 90 mEq. K, and chlorothiazide 1 Gm./day. When a weight loss of 1.5 kilograms or more has been achieved, generally after 3 days, the patient undergoes venous catheterization by the Seldinger technique under fluoroscopic control to allow blood sampling for measurement of renin activity from the renal veins and low inferior vena cava. Lateralization of the renal vein renin activity as demonstrated by a ratio of 1.5 to 1 (renal vein renin activity from the involved or more severely effected side to renal vein renin activity from the contralateral side) is a reliable indicator of the functional significance of renal artery obstructive lesions and is correlated with the results of separated renal function studies. Comparison of the contralateral renal vein renin activity with the renin activity in the inferior vena cava allows demonstration of suppression of renin release by the contralateral kidney in patients with surgically correctable unilateral renovascular hyper-

American Heart Journal

tension (because plasma renin activity from the low inferior vena cava is the same as plasma renin activity in arterial blood eritering the kidney2~). Perhaps soon, in general clinical use, will be 1sar, 8-ala angiotensin II (Pl13 or Saralasin), a potent polypeptide competitive inhibitor of angiotensin II in instances of high endogenous levels of angiotensin, for example, as in renovascular hypertension. In settings in which endogenous angiotensin II does not have an active role, this analogue has been shown to be an angiotensin agonist, increasing blood pressure in normal subjects. ~8, 2, Initial investigations indicate that, in sodium-depleted patients, a short infusion of this analogue may enable the clinician to identify more rapidly and directly the patients who are likely to have renin-dependent hypertension and who should undergo renal arteriography.

Management Observations that progression is the usual clinical course of renovascular disease indicate that medical or surgical treatment of renal artery stenosis does not cure the disease but provides some amelioration of an active and progressive process. When angiography demonstrates a characteristic lesion in a patient whose general health and life expectancy warrant consideration of surgical therapy, the functional significance and chances of surgical benefit are demonstrated by lateralization of the renal venous renin activity determinations2 ~ Thus; in the patient with moderate or severe hypertension and functionally significant stenotic lesions, the treatment of choice is surgical. Indeed, in some instances when medical therapy alone has been pursued in patients with high-grade stenosis effective blood pressure control, and hence decreased renal perfusion pressure, has contributed to loss of renal function secondary to progressive ischemic atrophy and fibrosis of the kidney beyond the stenosis. Successful surgical treatment of the stenosis has arrested progression of atrophy and, in some patients, h a s improved renal size and function. However, the enthusiastic desire to remove renovascular obstructions surgically must be tempered by the need to evaluate carefully the associated disease in other parts of the body and by the frequency of significant lesions among normotensive patients. 31

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Fig. 3. Fibromuscular renal artery stenosis. Sequential studies revealing minimally changed appearances of renal artery angiographically, but progressive renal atrophy of involved kidney. Surgical repair halted this progression.

Preservation of renal tissue has become the prime consideration in selecting therapy for renovascular hypertension because of the progressive nature of the disease on one hand and the frequently excellent response of blood pressure to rational medical therapy on the other22 In contrast to medical treatment, surgical therapy t h a t involves successful revascularization by any of many procedures has the advantage o f improvement or preservation of renal function, along with the amelioration of hypertension. Nephrectomy should be considered only in patients with extensive renal atrophy and a poor response to an intensive medical program. Results after 1 year of operative treatment of renovascular occlusive disease at 15 centers participating in the Cooperative Study of Renovascular Hypertension 33 sponsored by the National Heart Institute indicate that, in the patient with functionally significant unilateral fibromuscular disease, 90 per cent benefitted from surgery and were classified as cured or improved. Of patients with bilateral disease, 76 per cent ultimately benefitted from surgery. Surgical procedures included vein bypass grafts, Dacron bypass grafts, thromboendarterectomy, autogenous arterial bypass, and nephrectomy. Of 26 patients who underwent corrective surgery with an anatomically

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successful result, but who had no evidence of functional disparity by any of the diagnostic tests, only three were improved and 23 were failures. Other large series share this experience.~. 3~ Operative results in patients with atheromatous disease indicate that, while results are not as favorable as they are in fibromuscular disease, largely because of associated atheromatous disease and its complications elsewhere in the body, the great majority of patients with functionally important stenoses are cured or improved; most series report 80 to 90 per cent of patients in these groups. TM 33, 34 The surgical results of Ernst and co-workers 35 demonstrated this important point. In their group of patients with atheromatous disease localized to the renal artery, 87 per cent were classified as cured or improved and a 16 per cent operative mortality rate was noted. However, of the group with generalized disease, 53 per cent were cured or improved from surgery, and the surgical mortality rate was increased to 31 per cent. Follow-up periods were 55 and 41 months, respectively, for the two groups25 The series of reports by the Mayo Clinic group indicated that over a 7- to 14-year follow-up period, although blood pressure was controlled

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Fig. 3, cont'd. For Iegendsee preceding page.

medically, the surgically treated patients benefitted more both in long-term relief of hypertension and in reduced mortality rate. TM Over-all, the factors favoring a good surgical result are (1) youth, (2) increased severity of hypertension and refractoriness to medical treatment, (3) presence of fibromuscular disease rather than atheromatous disease, (4) a functionally significant lesion, and (5) the surgical possibility of repair, specifically, the surgical correction of associated aortic disease and the renal lesion during t h e same operation. 36 The effect of long-term medical management is revealed in the subsequent course of those hypertensive patients with renovascular disease who do not undergo operative treatment for one or more of several reasons: discordant arteriographic and renal functional data, renovascular lesions in the absence of significant stenosis or hypertension, the anatomic situation that technically would demand nephrectomy in the presence of a nonatrophic kidney, associated severe infirmities contraindicating surgery, or personal preference for medical therapy. Because of this selection process, these patients do not serve as a control group to the surgically treated patients: There is yet to be a true randomized prospective study. However, data obtained in this manner indicate t h a t blood pressure generally can be controlled medicallyJ8. 3~. 37Nevertheless, renal function can deteriorate in the presence of apparently

American Heart Journal

adequately controlled blood pressure, and the morbidity and mortality seem to increase over several years in the medically treated group TM (Figs. 3 and 4). The goal of medical treatment of hypertensive patients with renovascular disease should be to normalize the blood pressure (diastolic pressure < 90 mm. Hg). Comparison of data from surgical and treated 'groups indicates t h a t t h e surgical group had a blood pressure level about 20 mm. Hg lower than those treated medically. Also, the morbidity and mortality rate of target'organ damage from hypertension probably is reduced by normalization of the blood pressure, and medical treatment t h a t lowers the diastolic blood Pressure to only 100 mm. Hg probably is less effective. Hypertensive patients with normal renal function (serum creatinine level < 1.3 mg./dl.i should follow a controlled sodium diet in the range of 60 to 90 mEq.'/24 hr. as can be easily assessed by measuring 24-hour Urine sodium excretion. Some mild hypertensive patients may achieve normotension with dietary sodium control alone, b u t in most, this will serve to expedite further pharmacologic antihypertensive therapy. Moderate-tosevere hypertension may require multiple drug therapy, and diuretics plus agents t h a t interfere with renin release, such as a-methyldopa and propranolol, are particularly useful. 38 In patients with loss of renal reserve, several additional factors must be considered. Drug

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Fig. 4. Atheromatous renal artery stenosis. A, Excretory urogram at time of hypertensive evaluation. B, Repeat urogram 1 year !ater, while blood pressure was controlled on medical program. C, Angiogram obtained at that time revealing typical atherosclerotic involvement of aorta and renal arteries (both segmental and orificialstenoses).

therapy may frequently provide unwanted side effects in such patients: diuretics {such as the thiazides) may cause depletion of body potassium stores, hyperglycemia, and elevation of serum urate, which may progress to clinical gout. Therefore, a combination of dietary sodium restriction and nonkaliuretic diuretic agents may be useful, but caution is required because, when the serum creatinine level exceeds 4.0 mg./dl., the possibility of serious hyperkalemia exists.

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With more severe loss of renal function (serum creatinine level > 6.0 mg./dl, in women and > 8.0 mg./dl, in men), diuretics may cause depletion of body sodium and extracellular fluid volume with consequent further reduction of renal function. When this occurs, nondiuretic conservative management of renal failure and nondiuretic pharmacologic treatment for hypertension may be indicated. The intermittent administration of loop diuretics in combination with vasodilator antihypertensive medications such as hydralazine or minoxidi139 is useful in patients with hypertension and renal failure who do not respond to more conservative measures. If the renal failure or hypertension cannot be managed by these modalities, dialysis or transplantation should b e considered. Because of the observed clinical course, all patients, whether surgically or medically treated, require close continued observation after the initial management. Quantitative assessment of renal function by standard clearance techniques and by isotope renography should be performed at least yearly. Additionally, comparison of follow-up yearly roentgenograms of the kidneys with tomography gives important information regarding renal size. If renal mass is reduced or if renal function is diminishing, suggesting infarction or ischemic atrophy, arteriography should be repeated in order to reassess the original lesion or the current integrity of the surgical repair. Additionally, extrarenal arterial involvement by fibromuscular or atheromatous disease may become symptomatic. Current evidence justifies the vigorous approach to the management of severe renal artery stenosis and resultant moderate and severe renovascular hypertension by surgical means. Evidence is lacking for the use of this approach in the patient with less severe renovascular disease. If, in less severe renovascular disease, medical management maintains normal blood pressure and if on reevaluation there is no reduction in renal function, the continuation of such medical management is justified. If renal function is diminishing, or blood pressure has not been controlled at reassessment, then the aims of treatment, namely preservation of renal function and prevention of the morbid events resulting from uncontrolled hypertension, have not been met and surgical therapy should be considered after appropriate investigations.

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Summary Renal artery stenosis, either fibromuscular or a t h e r o m a t o u s , is p r o b a b l y t h e m o s t c o m m o n c a u s e o f s e c o n d a r y h y p e r t e n s i o n in m a n . B o t h o f these diseases are active, ongoing processes that m a y be a m e l i o r a t e d b u t n o t c u r e d b y m e d i c a l o r surgical treatment. The clinical history and examination of the patient with hypertension may help differentiate renovascular hypertension from essential hypert e n s i o n . T h e p r e s e n c e of a s y s t o l i c - d i a s t o l i c o r c o n t i n u o u s b r u i t is o f t e n a n i n d i c a t o r o f s e v e r e r e n a l a r t e r y stenosis: S y s t e m i c h y p e r t e n s i o n is t h e p h y s i o l o g i c c o n s e quence of significant renal artery stenosis. Knowledge of the basic concepts of the renin-am giotensin-aldosterone system, as has evolved from experimental models of renovascular hypert e n s i o n , f o r m s t h e b a s i s for u n d e r s t a n d i n g t h e process of evaluation and treatment of such patients. T h e t r e a t m e n t o f c h o i c e for t h e p a t i e n t w i t h severe hypertension and a functionally significant r e n o v a s c u l a r lesion is s u r g i c a l - b o t h in t e r m s o f successful treatment of hypertension and improved long-term prognosis. Diligent periodic reevaluation of these patients as well as those w i t h less s e v e r e h y p e r t e n s i o n w h o a r e r e c e i v i n g medical treatment enables the physician to select the proper management t h a t offers o p t i m a l control of patieni blood pressure and avoids target-organ damage to the kidneys, central nervous system, or cardiovascular system.

REFERENCES 1. Hunt, J. C., Bernatz, P. E., and Harrison, E. G., Jr.: -Factors determining diagnosis and choice of treatment Of renovascular hypertension: influence of location, severity, and type of stenosing lesions, Circ. Res. 21 (Suppl. 2):211, 1967. 2. Wallenweber, J., Sheps, S. G., and Davis, G. D.: Clinical course of atherosclerotic renovascular disease, Am. J. Cardiol. 21:60, 1968. 3. Harrison, E . G , Jr:, and Mc.C0rmack, L. J.: Pathologic classification of renal arterial disease in renovascular hypertension, Mayo Clin. Proc. 46:161, 1971, 4. Harrington, O. B., Crosby, V. G., and Nicholas, L.: Fibromuscular hyperplasia of the internal carotid artery, Ann. Thorac. Surg. 9:516, 1970. 5. Wylie; E. J., Binkley, F, M.' and Palubinskas, A. J.: Extrarenal fibr0muscular hyperplasia, Am. J. Surg. 1! 2:149, 1966. 6. Goldblatt, H.: Studies on experimental hypertension V. The pathogenesis of experimental hypertension due to renal ischemia, Ann. Intern, Med. 1 1:69, 1937. 7. Laragh, 3~ H., and Sealey, J: E.: The renin-angiotensin-aldosterone hormonal system and regulation o f

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December, 1977, Vol. 94, No. 6