Renovascular Hypertension

Updated: Jul 27, 2022
Author: Rebecca J Schmidt, DO, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FASN 


Practice Essentials

Renovascular hypertension (RVHT) reflects the causal relation between anatomically evident arterial occlusive disease and elevated blood pressure. The coexistence of renal arterial vascular (ie, renovascular) disease and hypertension roughly defines this type of nonessential hypertension.[1] More specific diagnoses are made retrospectively when hypertension improves after intravascular intervention.[2]

At present, no sufficiently accurate, noninvasive, radiologic, or serologic screening test is available that, if negative, completely excludes the presence of renal artery stenosis (RAS). Current guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) advocate screening for RAS only when a corrective procedure will be considered if renovascular disease is detected.[3]

When the history is highly suggestive and no risk of radiocontrast-mediated kidney injury is present, renal arteriography is the appropriate test. When a moderate suspicion of renovascular disease exists, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or duplex ultrasonography should be considered for screening, the latter depending on availability and local experience.

Antihypertensive drug therapy is indicated. Optimal blood pressure control plays an essential role in the therapeutic management of RVHT; however, aggressive control of other risk factors for atherosclerosis also is crucial. Cessation of smoking is important for its positive impact on the cardiovascular risk profile in patients with hypertension. Similarly, antidyslipidemic therapy for those patients with hyperlipidemia likely provides benefit in atherosclerotic RVHT.

The invasive and surgical options for treatment of RVHT include percutaneous transluminal renal angioplasty (PTRA), surgical revascularization, and nephrectomy. Intravascular stents may be placed during angioplasty, although research has called the clinical benefit of this into question. (See Treatment.)

Patient education regarding hypertension should include information about the clinical features associated with RVHT (see Presentation) and about the importance of good blood pressure control. For patient education information, see What Is Renal Hypertension?.


Since the seminal experimental work by Goldblatt and colleagues in 1934,[4] RVHT has increasingly been recognized as an important cause of clinically atypical hypertension and chronic kidney disease, the latter by virtue of renal ischemia. RVHT is the clinical consequence of activation of the renin-angiotensin-aldosterone system (RAAS).

Renal artery occlusion creates ischemia, which triggers the release of renin and a secondary elevation in blood pressure. Hyperreninemia promotes conversion of angiotensin I to angiotensin II, causing severe vasoconstriction and aldosterone release. The ensuing cascade of events varies, depending on the presence of a functioning contralateral kidney.

When two kidneys are present, aldosterone-mediated sodium and water retention is handled properly by the nonstenotic kidney, precluding volume from contributing to the angiotensin II–mediated hypertension. By contrast, a solitary ischemic kidney has little or no capacity for sodium and water excretion; allowing volume to play an additive role in the hypertension.


The chief pathophysiologic mechanism underlying RVHT involves activation of both limbs of the RAAS and depends on the presence or absence of a contralateral kidney (see the image below).

Proposed pathogenesis of renovascular hypertension Proposed pathogenesis of renovascular hypertension.

Unilateral renal ischemia initiates hypersecretion of renin, which accelerates conversion of angiotensin I to angiotensin II and enhances adrenal release of aldosterone. The result is profound angiotensin-mediated vasoconstriction and aldosterone-induced sodium and water retention.

In the two-kidney one-clip model, where the clinical correlate is unilateral renal artery disease, sodium and water handling via pressure diuresis of the contralateral kidney may be sufficient to prevent a volume component to the hypertension. In the setting of a solitary kidney (experimentally, the one-kidney one-clip model), sodium and water handling is compromised, sodium and water retention ensues, and volume-mediated hypertension occurs.

In unilateral RAS, renin production is increased in the ischemic kidney but suppressed in the unaffected nonstenotic kidney, which lacks the same ischemic stimulus. Consequently, when two kidneys are present with a unilateral stenosis (two-kidney one-clip model), hyperreninemia persists and blood pressure remains elevated because of an angiotensin II–induced vasoconstrictive effect. Renin production decreases in the contralateral kidney, a pressure diuresis ensues, and hypertension is maintained by high levels of angiotensin II.

A solitary kidney rendered ischemic by RAS is unable to achieve the pressure diuresis required to handle the aldosterone-induced sodium and water retention. The resultant volume expansion contributes to the elevation in blood pressure and also suppresses the production of renin by the stenotic kidney.

The sympathetic nervous system does not appear to play a role in perpetuating elevated blood pressure in the two-kidney one-clip model of RVHT. Evidence for a role in the one-kidney one-clip model of RVHT has been presented but is not clear or definitive.

Stages in development of renovascular hypertension

The evolution of RVHT [ref61], [ref62] has been described as having the following three stages or phases:

  1. Renin-angiotensin–dependent phase
  2. Salt-retention phase
  3. Systemic renin-angiotensin–independent phase

In the first phase, the immediate rise in blood pressure is a direct consequence of hyperreninemia. Over days to weeks, blood pressure remains elevated, but the course and presence of hyperreninemia vary with the presence and function of the contralateral kidney. The mechanism by which hypertension is produced in patients with renovascular disease thus changes over time and varies with the state of sodium balance.

When the contralateral kidney is functional, volume expansion is avoided and renin levels remain high. The two kidneys are in opposition; the stenotic kidney avidly retains sodium and produces excess renin in response to renal ischemia, while the nonstenotic kidney excretes sodium and water to maintain euvolemia and renin production decreases. The end result is systemic hypertension that is mediated by both renin and angiotensin.

In the second phase, in the setting of an ischemic solitary kidney, sodium and water retention, together with the vasopressor effects of angiotensin II, act to maintain renal perfusion pressure. The stimulus to produce renin is stifled, and renin levels fall. Hypertension becomes less dependent on angiotensin II and predominantly results from volume expansion. Thus, perfusion pressure is restored at the expense of systemic hypertension and volume overload.

If blood flow is restored during these first two phases and renal perfusion is reinstated, blood pressure soon returns to a normal level. If renal hypoperfusion persists and the third phase is reached, restoration of renal blood flow may not normalize blood pressure, presumably because of secondary irreversible vascular or renal parenchymal disease.

In the third phase, hypertension often is unremitting, persisting well after the removal of the stenosis. Recalcitrant hypertension in this setting likely represents the presence of ischemic nephropathy in either or both kidneys; patients in whom stenoses were not hemodynamically significant initially also may have persistent hypertension.

RAAS and control of intrarenal hemodynamics

Angiotensin II exerts a vasoconstrictive effect on both afferent and efferent arterioles, but because the efferent arteriole has a smaller basal diameter, the increase in efferent resistance exceeds the increase in afferent resistance. Afferent vasoconstriction is further minimized by angiotensin II–mediated release of vasodilatory prostaglandins and nitric oxide. In addition, angiotensin II can constrict the glomerular mesangium, thereby reducing the surface area available for filtration.

The net effect of angiotensin II on filtration invokes the opposing factors of reduced renal blood flow and mesangial surface area (causing a decrease in filtration) and the increase in glomerular capillary pressure (which tends to increase filtration). The end result depends on the clinical setting in which it occurs.

In the healthy kidney, a fall in systemic blood pressure activates the RAAS, which triggers a decrease in renal blood flow secondary to increased renal vascular (afferent) resistance. The preferential increase in efferent resistance mediated by angiotensin II results in increased glomerular capillary hydraulic pressure, which maintains the glomerular filtration rate (GFR).

In the ischemic kidney with reduced afferent blood flow, intraglomerular pressure and glomerular filtration are maintained by and depend upon angiotensin II–mediated efferent vasoconstriction. In this setting, removal of the efferent vasoconstrictive effect by angiotensin blockade, as achieved by angiotensin-converting enzyme (ACE) inhibitors, results in a decrease in intraglomerular pressure and GFR.

Thus, in patients with renovascular disease, particularly those with bilateral RAS or those with a stenotic renal artery to a single kidney, ACE inhibitors may cause a deterioration of renal function and azotemia. The propensity for angiotensin receptor blockers (ARBs) to affect GFR adversely is based on similar pathophysiology. It should be kept in mind that an acute decline in renal function in this setting is reversible once the ACE inhibitor (or the ARB) is discontinued.[2]


In adults, renovascular disease tends to appear at different times and affects the sexes differently. Atherosclerotic disease affects mainly the proximal third of the main renal artery and is most common among older men. Fibromuscular dysplasia (FMD) involves the distal two thirds and branches of the renal arteries and is most common among younger women. Midaortic syndrome is considered a variant of FMD. Neurofibromatosis may be seen.

Fibromuscular dysplasia 

FMD involves fibrous or muscular hypertrophy of the vessel tunica media with fibrous intimal hyperplasia; accordingly, it is sometimes referred to as fibromuscular hyperplasia. Often, poststenotic dilatation is also present. The process may range from mild occlusion to complete occlusion of the vessel. FMD may be multifocal or unifocal. Multifocal FMD, which is the more common form in adults, has the radiologic appearance of a so-called “string of beads”, while unifocal FMD appears as a circumferential or tubular stenosis.[2]  Louis et al reported that in children, unifocal FMD is more common than multifocal FMD, and the stenosis is often tubular.[5]

The most common site of stenosis is the orifice of the renal artery at its origin in the aortic wall (see the images below). The next most common location is within the main renal artery, and the segmental arteries are the least common site of stenosis. Total occlusion most often occurs at the orifice of the renal artery.

Aortogram of 4-year-old child with renovascular hy Aortogram of 4-year-old child with renovascular hypertension caused by stenosis of left renal artery. Note that left kidney has 2 renal arteries and that artery to superior pole has stenosis.
Close-up view of aortogram of 4-year-old child. St Close-up view of aortogram of 4-year-old child. Stenotic lesion begins at ostium of left superior renal artery. This lesion was caused by fibromuscular dysplasia and did not respond well to balloon angioplasty.

The inciting event of FMD is unknown. Some have suggested an autoimmune origin. In 1995, Stanley proposed that the lesion forms as a developmental disease in the muscular layer, which is followed by intimal hyperplasia from the abnormal flow through the constricted lumen.[6]

Midaortic syndrome 

In midaortic syndrome, vascular involvement extends beyond the renal artery. Aortic narrowing is present, often extending from the aortic hiatus to just above the inferior mesenteric artery (IMA). One or both of the renal arteries are usually involved, and the celiac artery and the superior mesenteric artery (SMA) may be narrowed. Midaortic syndrome may result in total renal artery occlusion, with perfusion dependent on collateral circulation. Extensive collateralization from the IMA and a Riolan arcade may exist. Renal artery stenosis is usually bilateral.[7, 8]


Hypertension in patients with neurofibromatosis is often essential, but some patients also present with RVHT (see the image below). These patients have a pattern of RAS similar to that observed in FMD. However, involvement of the intrarenal arteries and arterioles may also exist. Neurofibromatosis usually involves the renal arteries of both kidneys.[9]

Aortogram of 8-year-old child with neurofibromatos Aortogram of 8-year-old child with neurofibromatosis and renovascular hypertension caused by right renal artery stenosis.


The term renovascular hypertension (RVHT) implies that the cause of the elevated blood pressure is decreased arterial inflow to the kidneys. Overall, approximately 90% of RVHT cases are caused by atherosclerotic disease, 9% are caused by fibromuscular dysplasia (FMD), and miscellaneous causes make up the remainder.[2, 10] Other clinical entities that may be associated with RVHT include the following:

  • Cholesterol embolic disease
  • Acute arterial thrombosis or embolism
  • Aortic or renal artery dissection
  • Renal arterial trauma
  • Arterial aneurysm
  • Arteriovenous malformation of the renal artery
  • Diaphragmatic crus compression

Acquired RVHT may also be a consequence of:



United States statistics

RVHT is a common type of potentially correctable secondary hypertension. Although it accounts for less than 1% of mild hypertension, the prevalence may be as high as 38% in patients with severe hypertension and general atherosclerotic vascular or peripheral vascular disease.[11]  

The incidence of hypertension in children is reported to be 1-5%, and in adolescents may be as high as 10%. In children, unlike adults, 70-80% of hypertension may be secondary hypertension, which is often correctable. RVHT is second only to coarctation of the aorta as a surgically correctable cause of hypertension in children.[6]

International statistics

The prevalence of RVHT internationally is not clear, but it likely accounts for the sole etiology in a relatively small percentage of unselected patients with hypertension. Significant geographic differences in the overall prevalence of RVHT have not been reported, though the etiology does appear to vary geographically.

In the western hemisphere, FMD is the most common cause of pediatric RVHT. Reports from Asia and South Africa identify Takayasu arteritis affecting the renal artery as the most common cause of RVHT in children.[12]  One pediatric study in south Asia found that 87% of the patients presenting with RVHT had arteritis.[13]

Other demographics

The onset of RVHT tends to occur in patients younger than 30 years or older than 50 years. Systemic hypertension is less common in children than in adults, but the incidence of hypertension in children is approximately 1-5%. The presence of hypertension in younger children is usually indicative of an underlying disease process (secondary hypertension). In children, approximately 5-25% of secondary hypertension is attributed to renovascular disease.[14]

In children, the prevalence of renovascular disease as the cause of hypertension is inversely related to age with younger children more likely to have hypertension that is due to renovascular disease. In children younger than 5 years, the incidence of potentially surgically correctable hypertension is close to 80%. This incidence drops to 40-45% in children aged 6-10 years. In children aged 11-20 years, a 20% incidence of surgically correctable hypertension is observed.[14]

RVHT is most common in younger women and older adults.[11] Younger women develop RVHT most commonly from FMD affecting the distal two thirds and branches of the renal arteries. Older men develop RVHT most often from atherosclerotic disease affecting mainly the proximal third of the main renal artery. In children, multiple studies have failed to demonstrate any clear sex difference with regard to the prevalence of RVHT.

Overall, RVHT seems to be less common in the black population than in the white population.[15]  Blood pressure has been shown to be higher in black children than in white children, but the difference has not been deemed clinically significant. When adjusted for height, much of this difference is eliminated. RVHT is less common among older black children than among adolescent whites, but the prevalence is actually higher in young black children.[16]


The prognosis of patients with RVHT is difficult to ascertain and varies with the extent of the occlusive phenomena, the sensitivity of the individual to antihypertensive therapy, and the efficacy of surgical repair or angioplasty. In patients with hypertension, the presence of atherosclerotic renal artery disease is a strong predictor of increased mortality relative to the general population. RVHT in the setting of renal dysfunction is associated with the greatest mortality.

Although the actual mortality of untreated RVHT is not clear, the prognosis is clearly poor, and the severity of the hypertension places considerable amount of strain on target organs and can lead to death. Fortunately, renovascular disease may be correctable with surgical treatment or invasive intervention.

A retrospective review of a cohort that included 30 severely hypertensive children with renovascular disease found an overall 18% incidence of hypertensive retinopathy. Most of the children had severe disease (retinal hemorrhages, exudates, and optic disc edema) and in some cases permanent visual reduction.[17]

PTRA yields normal blood pressures in some patients and others experience a decrease in blood pressures. Unfortunately, a high rate of recurrence of hypertension and vascular stenosis appears to be observed in patients treated with PTRA.[18] Some patients may experience resolution of their hypertension after nephrectomy.

Revascularization using PTRA with or without stenting in combination with medical therapy has been investigated in randomized trials of patients with unilateral atherosclerotic renal artery stenosis.  A meta-analysis of these trials found no benefit from PTRA on mortality or end-stage renal disease as major cardiovascular events.[19]

Patients who have a high likelihood of benefit from revascularization with PTRA with stenting and medical therapy versus medical therapy alone are those that have unilateral renal artery stenosis, bilateral renal artery stenosis, or stenosis of a solitary kidney and meet one or more of the following criteria[13] :

  1. Recurrent congestive heart failure or sudden unexplained pulmonary edema
  2. Unstable angina
  3. Accelerated, resistant, or malignant hypertension
  4. Hypertension with unexplained unilateral small kidney and intolerance to medication

Successful surgical intervention is expected to offer patients a normal lifespan without complications. Children who undergo surgical revascularization appear to do well for at least 16 years postoperatively. They are able to participate in active sports and similar vigorous activities without problems. Further long-term follow-up is needed to determine the durability of these reconstructions and the actual life potential of these children.




Patients with RVHT may be asymptomatic, and the hypertension may be discovered during routine examination or preparation for surgical treatment of another problem. In most pediatric studies, more than one half of children who were found to be hypertensive were asymptomatic, or their hypertension was discovered during a routine examination. When symptoms are present, they are often nonspecific and are related to the organ systems most affected by hypertension.

Neurologic may manifestations include headache, altered mental status, vision changes, vomiting, seizures, coma, encephalopathy, hyperexcitability, and hyperirritability. Signs and symptoms of congestive heart failure (eg, decreased energy, edema, and shortness of breath) may also develop. In patients with abdominal aortic narrowing, claudication may be present. Some children have anorexia, and infants or young children often present with failure to thrive. Occasionally, patients have oliguric renal failure.

Clinical risk factors for RVHT include the following:

  • A history of hypertension with azotemia (serum creatinine level >1.5 mg/dL) and modest proteinuria (levels < 1.5 g/day)
  • Progressive renal insufficiency
  • Accelerated or malignant hypertension
  • Severe hypertension (diastolic blood pressure >120 mm Hg)
  • Hypertension with an asymmetric kidney
  • Paradoxical worsening of hypertension with diuretic therapy
  • Hypertension refractory to standard therapy

The following are common findings from the history:

  • Onset of hypertension in patients younger than 30 years without risk factors

  • Abrupt onset of severe (stage II) hypertension (greater than 160/100 mm Hg in patients older than 55 years)

  • Severe or resistant hypertension despite appropriately dosed multidrug (>3 agents) antihypertensive therapy

  • Abrupt increase in blood pressure over previously stable baseline in patients with previously well-controlled essential hypertension, as well as patients with known renal artery stenosis (RAS)

  • Negative family history for hypertension

  • Smoking tobacco products

  • Acute sustained rise in serum creatinine levels with angiotensin-converting enzyme (ACE) inhibitor therapy

  • Unprovoked hypokalemia (serum potassium level < 3.6 mEq/L, often associated with metabolic alkalosis)

  • Symptoms of atherosclerotic disease at other sites, in the presence of moderate-to-severe hypertension, particularly in patients older than 50 years

  • Recurrent pulmonary edema in the setting of moderate-to-severe hypertension

  • Moderate-to-severe hypertension in a patient with an unexplained atrophic kidney, significantly asymmetric kidneys (> 1.5 cm difference), or diffuse atherosclerosis

Physical Examination

Findings suggestive of long-standing hypertension may or may not be evident upon physical examination. Such findings may include the following:

  • Recurrent flash pulmonary edema or unexplained episodes of congestive heart failure

  • Advanced funduscopic changes

  • Abdominal bruit – A clear abdominal bruit may be heard in 46% of patients with RVHT, however, innocent bruits are common in younger individuals; systolic-diastolic bruits in combination with hypertension are suggestive of RVHT

On physical examination, pediatric patients with RVHT have a blood pressure elevation above the 95th percentile for their age, sex, and height. Generally, children with blood pressures higher than 140/100 mm Hg are thought to be more likely to have secondary hypertension, and RVHT is more likely in children with higher blood pressure.[16, 20]

Eye examination may reveal retinopathy and retinal hemorrhages. Patients with heart failure may present with tachypnea, cardiomegaly, and vasomotor instability leading to mottling and acrocyanosis. Lower-extremity pulses may be diminished with aortic coarctation, whether thoracic or abdominal.

An enlarged liver may be palpated, and an abdominal bruit may be auscultated. Patients with tumors impinging on renal vasculature may present with an abdominal mass in the area of the kidney. Rarely, signs or symptoms of visceral artery involvement are present because of the extensive collateralization that occurs.

Café-au-lait macules are classic findings in the presentation of neurofibromatosis. Patients with neurofibromatosis may also have macrocephaly, neurofibromas, dermal neurofibromas, and axillary freckling.


Left untreated, RVHT can produce serious consequences associated with hypertensive crisis including coma and death. Chronic hypertension can damage blood vessels, leading to such pathology as plaques, aneurysms, claudication, and dissection.

The main comorbidity of RVHT is directly related to its capacity to lead to end-organ damage. Neurologic manifestations are often the presenting symptoms because severe hypertension can lead to retinopathy, headaches, dizziness, confusion, seizures, and stroke. The heart is frequently affected because increased afterload leads to congestive heart failure and ventricular hypertrophy.

RVHT may also damage the kidneys, especially when significant stenosis of the perfusing vessels is present to cause ischemia.

Finally, RVHT is often associated with failure to thrive in young children.



Diagnostic Considerations

Clues to the presence of RVHT that might lead to serious complications (eg, stroke, renal failure, and cardiac decompensation) include the following:

  • Recurrent and otherwise unexplained flash pulmonary edema or heart failure
  • Recalcitrant hypertension that previously was controlled easily
  • Hypertension that abruptly becomes more difficult to control and requires increased antihypertensive agents
  • Slowly increasing serum creatinine levels, signifying the evolution of ischemic nephropathy

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Adrenal tumor
  • Aldosteronoma
  • Aortic insufficiency
  • Arterial hypoplasia
  • Cushing disease
  • Cushing syndrome
  • Essential hypertension
  • Fibromuscular dysplasia
  • Increased intracranial pressure
  • Intracranial mass
  • Irradiation
  • Moyamoya disease
  • Other nonessential forms of hypertension
  • Renal cyst
  • Renal failure
  • Renal hypoplasia
  • Renal parenchymal disease
  • Retinopathy
  • Stroke
  • Thrombosis
  • Umbilical catheter embolism

Differential Diagnoses



Approach Considerations

It is useful to determine the clinical risks for renovascular hypertension (RVHT) before embarking on an extensive workup that may not be productive or cost-effective. Patients in whom a definitive noninvasive or invasive workup is indicated are those in whom suggestive clinical features have been identified in the course of the history and physical examination (see Presentation).

At present, no sufficiently accurate, noninvasive, radiologic, or serologic screening test is available that, if negative, completely excludes the presence of renal artery stenosis (RAS).[21] Current guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) advocate screening for RAS only for patients in whom a corrective procedure would be considered if renovascular disease were detected.[3]   Testing is not recommended in patients whose hypertension is responsive to medication and those in whom there is not a high likelihood of clinically significant renovascular disease. 

Guidelines from the ACC/AHA and the European Society of Cardiology (ESC) recommend performing diagnostic studies to identify RAS in patients with any of the following[3, 22] :

  • Onset of hypertension before the age of 30
  • Onset of severe hypertension after the age of 55
  • Accelerated hypertension (sudden and persistent worsening of previously controlled hypertension)
  • Resistant hypertension (failure of blood-pressure control despite full doses of an appropriate three-drug regimen including a diuretic)
  • Malignant hypertension (hypertension with coexistent end-organ damage;  ie, acute kidney injury, flash pulmonary edema, hypertensive left ventricular failure, aortic dissection, new visual or neurological disturbance, and/or advanced retinopathy)
  • New azotemia or worsening renal function after the administration of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB)
  • Unexplained atrophic kidney or size discrepancy of greater than 1.5 cm between the kidneys
  • Unexplained renal failure thought to be a consequence of renovascular disease

The ACC/AHA guidelines also include patients with sudden, unexplained pulmonary edema in its class I recommendations.[3] The ESC recommendation include patients with hypertension and abdominal bruit as well as those with hypertension and hypokalemia in particular when receiving thiazide diuretics.[22]



As a screening test for RAS, the ACC/AHA guidelines recommend duplex ultrasonography.[3]  The advantages of duplex ultrasonography include lack of radiation, high sensitivity and specificity, low expense, and ability to be repeated without risk or discomfort to the patient.[23]   Disadvantages include that it is time consuming, operator dependent, and technically difficult in obese patients.

Other recommended screening tests include computed tomographic angiography (CTA), in patients with normal renal function, and magnetic resonance angiography. When the results of noninvasive screening tests are inconclusive and the clinical index of suspicion is high, angiography is recommended to establish the diagnosis of RAS.[3]  However, because of the risks associated with radiocontrast, angiography is imposed only on those individuals most likely to benefit.

Tests that are not recommended for RAS screening include captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity, and measurement of plasma renin activity after captopril administration (the captopril test).[3]

See Imaging in Renal Artery Stenosis/Renovascular Hypertension for a complete discussion of this topic.

For pediatric RVHT, basic diagnostic tests should accomplish the following two objectives:

  • Detect any unsuspected renal parenchymal disease (because the most common medical cause of hypertension in children is renal disease)

  • Identify the presence of any end-organ damage due to the hypertension

Patients should be transferred to another facility whenever the current facility lacks the capacity to perform the testing necessary to confirm or refute the diagnosis of RVHT or to assess the severity of a confirmed diagnosis of RVHT.

Many authors believe that diagnostic imaging should begin with doppler ultrasonography of the kidneys and abdomen, which is useful in identifying renal disease and abdominal masses. This technique potentially can detect both unilateral and bilateral disease and also can be used to detect recurrent stenosis in patients previously treated with angioplasty or surgery. It should be kept in mind, however, that renal ultrasonographic findings are insufficient to rule out the need for angiography.

Doppler ultrasonography provides both anatomic and functional assessment of the renal arteries. Direct visualization of the main renal arteries (B-mode imaging) is combined with measurement (via Doppler) of intrarenal pressures and velocities (by waveform) to achieve a sensitivity of 72-92% for detecting RAS of 70% or greater.

Doppler ultrasonographic evaluation of renal resistance indices (1 – end diastolic velocity/maximum systolic velocity × 100) can be used to classify patients as potential responders or nonresponders to intervention (ie, a renal resistance index exceeding 80% implies a low likelihood that correction of the stenosis will eventuate in improved blood pressure control or kidney function).[24, 25, 26]

Important disadvantages of this modality include the possibility that bowel gas can interfere with direct visualization of the renal arteries (50-90% of the time). Doppler measurements are hampered very infrequently (0-2%). Furthermore, this modality is time-consuming to perform (requiring approximately 2 hours) and is a technically difficult procedure with a steep learning curve, making success highly operator-dependent.

Laboratory Studies

Laboratory studies mentioned are often done for completeness and for historical context and are not considered useful as screening tests. Initial tests for both adults and children with hypertension include[27] :

In addition, a fasting lipid panel and fasting glucose level are recommended for the following[27] :

  • Overweight patients whose blood pressure is at the 90th–94 th percentile
  • All patients with blood pressure at the 95th percentile or higher
  • Patients with a family history of hypertension or cardiovascular disease
  • Children with chronic kidney disease

Kidney function test results frequently yield normal results in children with renovascular disease, even when the lesions are bilateral. Findings on a 24-hour urine study should also be within the reference range in RVHT.

The CBC, serum electrolyte levels, BUN levels, and serum creatinine levels should indicate the presence of renal function impairment or whether a pattern of hyperaldosteronism is present.

A 24-hour urine sample for electrolytes, creatinine, vanillylmandelic acid, catecholamines, 17-hydroxy steroids, and 17-keto steroids should be considered in patients with elevated blood pressure that is not typical of essential hypertension or RVHT.  Normal results should rule out the possibility of a medullary or cortical tumor.

The erythrocyte sedimentation rate (ESR) may be elevated in active arteritis.


Imaging Studies

Selective renal arteriography is still widely considered the gold standard for diagnosis of RVHT. Renal arteriography is necessary whenever surgery or percutaneous transluminal angioplasty is anticipated.  Because this is a highly invasive procedure, it is appropriate to perform screening and less specific tests in order to refine the level of suspicion for disease that might me amenable to treatment.

Computed tomographic angiography

Spiral CT scan with intravenous contrast (CT angiography) is highy accurate in diagnosing atherosclerotic renovascular disease.[28]   Adding digital subtraction angiography (DSA) technology to renal arteriography requires one half the volume of dilute contrast medium that standard arteriography requires, while yielding comparable results.  Because intra-arterial DSA requires less radiocontrast (25-50 mL) than conventional angiography (100 mL), it is preferred for patients with compromised kidney function. RAS of 70% or more or stenosis of 50% with poststenotic dilatation is considered hemodynamically significant.

Intravenous (IV) DSA has also been suggested for identification of renovascular disease. It is less invasive than intra-arterial DSA but requires more radiocontrast. Yield depends on the skill of the individual interpreting the radiograph, and image quality is diminished by interference from patient or intestinal motion or gas (which can be reduced by abdominal pressure and glucagon), as well as by overlying vessels and poor cardiac output. Compared with arterial studies, IV DSA has a sensitivity and specificity of 90% or less and thus is not commonly used.

Magnetic resonance angiography

MRA is increasingly reported to provide better results than noninvasive screening procedures.[29]  Studies indicate that 3-dimensional MRA with gadolinium-based contrast agents has a sensitivity of 96-100% and a specificity of 71-96% for the detection of a main RAS of greater than 50% (see the image below).[30, 31, 32]  Concerns for severe dermatologic side effects when used in patients with reduced kidney function have led to avoidance of these agents though recent studies favor a more permissive approach with certain types of gadolinium-based contrast.[33, 34]

Magnetic resonance angiography (MRA) showing renal Magnetic resonance angiography (MRA) showing renal artery stenosis. Courtesy of Patricia Stoltzfus, MD, Chief of Interventional Radiology, West Virginia University.

When combined with cardiac synchronization, 3-dimensional MRA can sharply delineate the entire length of the major renal arteries. However, it remains suboptimal for the detection of hemodynamically significant lesions of distal, intrarenal, and accessory renal arteries, which, for all purposes, behave pathophysiologically as RAS. MRA is also of limited value in fibromuscular dysplasia (FMD), in which the lesions, being primarily middle and distal, are less well visualized with this modality.

Limitations of MRA include relatively high cost, restricted availability and concerns for long-term dermatologic side effects when used in patients with poor kidney function. Contraindications to MRA include claustrophobia and the presence of a metallic implant (eg, a pacemaker or surgical clip). The risk-to-benefit ratio should be carefully considered in patients with reduced kidney function and in patients on hemodialysis should be dialyzed daily for three days after receipt of this agent.


Other Tests


Because of its high false-negative rate (20-25%), the nonstimulated renal scan has limited efficacy and is not universally recommended as a screening test. The predictive value of radioisotope scanning, however, can be enhanced by the administration of captopril orally (25-50 mg) 1 hour before the isotope is injected. Decreased function after treatment with captopril indicates a high likelihood of renovascular stenosis. If the scan findings remain normal, renovascular disease is not ruled out.

Stratigis et al reported that in patients with atherosclerotic renal artery stenosis, captopril renal scintigraphy can accurately identify patients who are likely to benefit clinically from percutaneous renal artery revascularization, by identifying hemodynamically significant stenosis. Their study of 64 patients with a high coronary artery disease burden who underwent baseline captopril renal scintigraphy followed by renal angiography found that in the patients with atherosclerotic renal artery stenosis of 70% or greater, captopril renal scintigraphy positivity had 100% sensitivity and specificity for both a hypertension and kidney function benefit from revascularization.[35]

A marker of glomerular filtration (eg, diethylenetriamine pentaacetic acid [DTPA]) or compounds that are secreted by the proximal tubule (eg, hippurate, mercaptotriglycylglycine [MAG-3]) can be used to estimate total, as well as differential, kidney function—information that may be useful in the assessment of treatment options. The latter may be more reliable in patients with renal insufficiency. Removal of angiotensin II–mediated vasoconstriction by ACE inhibition induces a decline in the GFR of the stenotic kidney and often an equivalent increase in the GFR of the contralateral kidney. The difference in the GFR between the 2 kidneys is enhanced by radioisotope and is visible on the renogram.

Positive results from an ACE inhibitor renogram are determined according to the following 2 criteria:

  • Relative uptake of the isotope decreased, with 1 kidney accounting for less than 40% of the total GFR
  • Peak uptake of the isotope delayed to more than 10-11 minutes (normal, 3-6 minutes)

A slower washout of the isotope may occur in the stenotic kidney, as demonstrated in unilateral RAS by a delay of 5 minutes or longer in washout on the involved side. This criterion may be evaluated best with a compound such as hippurate, which is secreted into the tubules rather than only being filtered.

While the availability of more sophisticated imaging along with a number of limitations have relegated the renogram away from favor as a screening test for RVHT, it remains useful for determining differential (relative) function of each kidney in settings where a nephrectomy is contemplated.

Plasma renin activity

The baseline plasma renin activity (PRA) is elevated in 50-80% of patients with RVHT [37]. Renin levels may be increased or decreased by all antihypertensive agents. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease plasma renin levels. Measuring the rise in the PRA 1 hour after administering 25-50 mg of captopril can increase the predictive value of the test. Patients with RAS have an exaggerated increase in PRA, perhaps due to removal of the normal suppressive effect of high angiotensin II levels on renin secretion in the stenotic kidney.

The sensitivity and specificity of studies of the captopril renin test are 75-100% and 60-95%, respectively. Limitations include the need to discontinue antihypertensive medications that can affect the PRA (eg, ACE inhibitors, beta-blockers, and diuretics), the low sensitivity, and the somewhat decreased predictive value when compared to a renogram after ACE inhibition [37].

Although elevation of peripheral or renal vein PRA has been used to diagnose unilateral renal disease and predict surgical curability, an elevated plasma renin level does not establish the cause of hypertension, and levels that are within the reference range do not rule out renovascular disease [38].

Renal vein renin ratio

Renal vein renin measurements compare renin release from the 2 kidneys and are used to predict the potential success of surgical revascularization. Renin secretion is increased in the ischemic kidney but is suppressed in the contralateral kidney, as evidenced by the similar levels of renin measured in the renal artery (infrarenal inferior vena cava) and the renal vein.

The ratio of the measurement from the ischemic kidney to the measurement from the contralateral kidney is the renal vein renin ratio. A ratio higher than 1.5 constitutes a positive test result and is suggestive of functionally important renovascular disease. Volume depletion exaggerates reduced renal perfusion and may increase the renal vein renin ratio in asymmetric disease.

Fewer than 10% of healthy patients have a renal vein renin ratio higher than 1.5, and less than 20% have a ratio lower than 1.1. It has been suggested that the accuracy of these measurements can be enhanced by prior administration of an angiotensin-converting enzyme (ACE) inhibitor, which will increase renin secretion on the affected side.

False-negative and false-positive results are common.[36] Although more than 90% of patients with unilateral RAS and lateralizing renin values respond positively to angioplasty or surgery, about 50% of those with nonlateralizing findings also benefit from correction of the stenosis.[11]

As a result, most physicians rely on the clinical index of suspicion rather than on renal vein renin measurements to estimate the physiologic significance of a stenotic lesion. An exception may occur in patients with bilateral RAS, in whom renal vein renin measurements can be used to determine the side that most contributes to the hypertension.[11]

Carbon dioxide angiography

Carbon dioxide gas has been used in combination with iodinated contrast agents for angiography in the treatment of RAS, including post-transplant RAS, since late 1990s, with some success.[37, 38, 39, 40]  This approach allows a reduction in the amount of iodinated contrast needed, thus decreasing the risk of contrast-induced acute kidney injury.

Carbon dioxide angiography is not completely risk free, however; it has been linked to mesenteric ischemia, non-fatal myocardial infarction, and respiratory failure, and its use in procedures above diaphragm is contraindicated.[41]  The increased availability of low osmolar agents along with lack of training in the use of this modality has likely led to its infrequent use, though it remains an option for patients at higher risk of contrast-associated acute kidney injury.



Approach Considerations

Antihypertensive drug therapy is indicated. Optimal blood pressure control plays an essential role in the therapeutic management of renovascular hypertension (RVHT), with renin-angiotensin-aldosterone system (RAAS) blockers (ie, angiotensin-converting enzyme inhibitors [ACEi], angiotensin receptor blockers [ARBs]) considered the first-line drugs in this setting.[42]

Aggressive control of other risk factors for atherosclerosis is also crucial. Cessation of smoking is important for its positive impact on the cardiovascular risk profile in patients with hypertension. Similarly, antidyslipidemic therapy for those patients with hyperlipidemia likely provides benefit in atherosclerotic RVHT. In patients with fibromuscular dysplasia, antiplatelet therapy (typically, aspirin 75–100 mg daily), if not contraindicated, is reasonable to prevent thrombotic and thromboembolic complications.[43]

Progression of atherosclerotic stenosis may occur in as many as one third of patients, and the sequelae of ongoing ischemia to the stenotic kidney are a theoretical concern. Furthermore, normalization of blood pressure may be associated with reduced renal perfusion pressures, and kidney function may deteriorate despite good blood pressure control.

Definitive therapy for the underlying cause must be considered in order to avoid the development of ischemic nephropathy.[11] Intervention to treat hemodynamically significant stenoses has been presumed to offer clinical benefit; however, trials comparing renal artery revascularization with medical management do not unequivocally favor surgical over medical intervention, suggesting the need for research to identify patients most likely to benefit from intervention.[18, 44] A Kidney Disease: Improving Global Outcomes (KDIGO) consensus statement lists the following as definite indications for revascularization in patients with atherosclerotic renovascular disease[42] :

  • Acute pulmonary edema or acute decompensations of heart failure in a patient with high-grade renal artery stenosis (RAS)
  • Progressive chronic kidney disease (CKD) in a patient with high-grade (> 75%) RAS (bilateral or solitary kidney)
  • Acute kidney injury (AKI) due to acute renal artery occlusion or high-grade RAS
  • ACEi or ARB intolerance in a patient with high-grade RAS
  • RAS (symptomatic or asymptomatic) in a kidney transplant recipient

Possible indications for revascularization, according to KDIGO, are as follows[42] :

  • Chronic heart failure and high-grade RAS
  • Coexistence of progressive CKD and uncontrolled hypertension
  • Asymptomatic high-grade RAS (bilateral or supplying a solitary kidney) with viable renal parenchyma (to prevent atrophy)
  • Nonfunctioning but possibly viable kidney in a patient who has been receiving dialysis for less than 3 months

The invasive and surgical options for treatment of renovascular hypertension include the following[45] :

  • Percutaneous transluminal angioplasty (PTA)
  • Surgical revascularization
  • Nephrectomy

Catheter-based radiofrequency denervation of the renal arteries has entered clinical use in many countries as a treatment for resistant hypertension. The SYMPLICITY HTN-3 trial randomized 535 patients with severe resistant hypertension and found that catheter-based radiofrequency denervation of the renal arteries was safe but did not result in a significant reduction of systolic blood pressure 6 months post-procedure, as compared with a sham control.[46] Subsequent reviews, however, have shown that renal denervation was not effectively or consistently achieved in the trial.[47]

The patient should be transferred to a tertiary care medical facility whenever the need for invasive or surgical treatments has been established and the current treating facility is not equipped for such procedures.

Inpatient care usually is necessary for the management of hypertensive urgencies or emergencies associated with RVHT. Timely diagnosis of RVHT and early intervention are required to prevent further ischemic end-organ damage to the kidney and other organs.

Pharmacologic Therapy

Hypertensive patients should receive antihypertensive medication. In children with severe hypertension, it may be necessary to initiate medical treatment before a definitive diagnosis is obtained.

RVHT is often refractory to medical treatment. Because current approaches to renal artery dilation and surgical revascularization yield excellent results, these procedures are generally considered the treatments of choice in preference to life-long antihypertensive medication that does not achieve optimal blood pressure control. However, attempts to control the patient’s blood pressure in preparation for surgical intervention should always be made. In particular, it is advisable to defer surgery until manifestations of malignant hypertension are relieved.

All classes of antihypertensive medications are used to treat RVHT, and multiple drugs may be used initially. However, the most effective therapy is with ACEi, which minimize the ischemia-induced rise in angiotensin production. There has been less clinical experience with ARBs, but these agents appear to be as effective as ACEi.

Most patients with RVHT tolerate RAAS blockers well. However, in individuals with marginal renal perfusion pressure, sodium depletion, or both, glomerular filtration depends on the action of angiotensin II, and in that setting, ACEi and ARBs may markedly decrease renal blood flow, with an ensuing deterioration in kidney function. However, in patients with high-grade RAS, therapy with any antihypertensive drug may result in further reductions in renal blood flow and loss of kidney function.[42]

Certainly, any patients with RVHT who are treated with an ACEi or ARB should have their serum creatinine levels monitored, and therapy should be discontinued if their creatinine levels rise significantly. In patients without hemodynamically significant RAS, a serum creatinine increase of up to 35% above baseline with an ACEi or an ARB is considered acceptable and is not a reason to withhold treatment unless hyperkalemia develops.

Both beta blockers and diuretics also are used, the latter often in conjunction with ACEi. Diuretics enhance sodium and water diuresis, thereby eliminating the volume-mediated component of RVHT. Calcium channel blockers may provide equally good control of hypertension while presumably causing less impairment of the function of the ischemic kidney than ACEi do. Nitroprusside and phenoxybenzamine are useful in the short-term management of malignant hypertension before surgery.

The selective aldosterone inhibitor eplerenone is also available for the treatment of hypertension. This agent selectively blocks aldosterone at the mineralocorticoid receptors in both epithelial tissues (eg, kidney) and nonepithelial tissues (eg, heart, blood vessels, and brain), thereby decreasing blood pressure and sodium reabsorption. The adult dosage is 50 mg/day orally, which may be increased after 4 weeks to a dosage not exceeding 100 mg/day. Contraindications include the following:

  • Documented hypersensitivity
  • Hyperkalemia
  • Coadministration with drugs causing increased serum potassium levels
  • Moderate-to-severe reduction in renal function (ie, creatinine clearance less than 30 mL/min)

Because eplerenone is a cytochrome P-450 (CYP450) 3A4 substrate, potent CYP3A4 inhibitors (eg, ketoconazole) increase serum levels of the drug about 5-fold, whereas less potent CYP3A4 inhibitors (eg, erythromycin, saquinavir, verapamil, and fluconazole) increase serum levels about 2-fold. Grapefruit juice increases serum eplerenone levels by about 25%.

Coadministration of eplerenone with potassium supplements, salt substitutes, or drugs known to increase serum potassium (eg, amiloride, spironolactone, triamterene, ACEi, and ARBs) and increases the risk of hyperkalemia. Eplerenone may cause hyperkalemia, headache, or dizziness. Caution is advised in patients with hepatic insufficiency.

Percutaneous Transluminal Angioplasty

PTA is a therapeutic nonsurgical procedure using pressure expansion of a small balloon on a special vascular catheter to dilate narrow areas in a blood vessel. PTA is less expensive and less invasive than surgical revascularization and can be performed at the time of angiography. If the stenosis is refractory to treatment or if restenosis develops, surgical revascularization can still be performed.

In patients with RVHT, PTA is performed to open stenotic renal arteries (percutaneous transluminal renal angioplasty [PTRA]), the most amenable lesions being those without total occlusion. PTRA is most effective against midvessel stenosis. Lesions involving segmental arteries or the ostia of renal arteries and lesions in patients with neurofibromatosis are especially refractory to balloon angioplasty.

Outcomes appear to be significantly better in patients with fibromuscular dysplasia (FMD) than in those with atherosclerotic stenosis. A systematic review and meta-analysis found that after PTRA, hypertension was cured in 37% of patients with FMD and improved in 80%, although rates varied highly across studies.[48] Restenosis necessitating repeat angioplasty has been reported in fewer than 10% of patients with FMD and in 8-30% of those with atherosclerotic stenosis.[49]

A Swedish study of 105 patients treated with PTRA reported a 5-year survival rate of 83% for patients with arteriosclerotic renovascular disease.[50] The rate for patients with fibromuscular vascular disease was even higher, reaching 100%.

PTRA has yielded mixed results in children. Long-term maintenance of blood pressure improvement ranges from 38% to 90%. Guzzetta et al[51] and Tyagi et al[13] found that approximately 25% of patients treated with PTRA developed restenosis. Casalini et al, evaluating PTRA in a selected group of 36 children with RVHT, found that 34 (94%) of the patients were normotensive 2 years after the procedure.[52]

The results of PTRA in patients with bilateral renal artery disease have been relatively poor, suggesting that surgical intervention should be a strong consideration in this setting. In patients with diffuse atherosclerosis, the complication rate is relatively high with either surgery or angioplasty; medical therapy may be preferred in this setting.

Renal stents

Placement of intravascular stents during angioplasty (see the images below) may be helpful in preventing restenosis and managing RVHT. Data suggest that stenting may prove useful in patients with ostial disease, those who develop restenosis after PTRA, or those with complications resulting from PTRA (eg, dissection). Primary renal artery stenting in patients with atherosclerotic RAS has a high rate of technical success and a low rate of complications.[53, 54, 55]

Angiogram showing bilateral renal artery stenosis. Angiogram showing bilateral renal artery stenosis. Courtesy of Department of Radiology, Henry Ford Hospital.
After percutaneous transluminal angioplasty (right After percutaneous transluminal angioplasty (right renal artery). Courtesy of Department of Radiology, Henry Ford Hospital.
After percutaneous transluminal angioplasty and st After percutaneous transluminal angioplasty and stent placement (left renal artery). Courtesy of Department of Radiology, Henry Ford Hospital.

The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial—a randomized, unblinded trial in 806 patients with atherosclerotic renovascular disease that compared revascularization (PTRA with or without stenting) plus medical therapy with medical therapy alone—found substantial risks but no evidence of a worthwhile clinical benefit from revascularization. Over a 5-year period, the two patient groups showed no statistically significant difference in systolic blood pressure or in the rate of progression of renal impairment, renal or major cardiovascular events, or death.[56]

Similarly, the addition of renal artery stenting to comprehensive medical therapy provided no significant clinical benefit in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study, which included 947 patients with atherosclerotic renal artery stenosis and hypertension or chronic kidney disease. Despite a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg), there was no significant difference in adverse cardiovascular and renal events or all-cause mortality.[57]

Saad and colleagues have offered a partial explanation for the limited clinical benefit of renal stenting. These researchers reported that severe renovascular disease is associated with tissue hypoxia and increased levels of renal venous markers of inflammatory cytokines and tissue injury. In their study, revascularization reduced hypoxia and partially restored blood flow, but failed to alter markers of inflammation, suggesting that additional measures may be needed to reverse the process of kidney injury.[58]

Other authors have proposed that stenting may be beneficial in carefully selected patient subgroups. Noory et al suggest that patients with hemodynamically significant RAS who have progressive renal insufficiency and/or deteriorating arterial hypertension may derive clinical benefit from stent revascularization.[59]

According to a consensus statement from the Society for Cardiovascular Angiography and Interventions (SCAI), the strongest evidence supporting renal artery stenting for RAS is in patients with a cardiac disturbance syndrome or flash pulmonary edema. In addition, carefully selected patients with severe bilateral RAS or stenosis to a solitary functioning kidney may experience clinical improvement with renal artery stenting.[23]

Other cases in which renal artery stenting generally represents appropriate care after a trial of optimal medical therapy, according to the SCAI, include the following[23] :

  • Patients with accelerated or resistant hypertension (failure of ≥3 maximally tolerated medications including the use of a diuretic)
  • Global renal ischemia (bilateral RAS or severe RAS in a solitary functioning kidney)
  • Hypertension with medication intolerance

Sustained benefit of renal artery stenting was shown in a retrospective study of 26 patients with ≥70% stenosis and uncontrolled systolic hypertension despite three or more antihypertensive drugs. On m[43] edian follow-up of 5.1 years, blood pressure reduction was sustained (135/70 ± 18/11 mmHg) compared with initial reduction at 6 months and from baseline (162/80 ± 24/18 mmHg). The patients were also taking fewer antihypertensive drugs than at baseline (2.7 ± 2.1, down from 4.1 ± 1.0).[60]

In patients with FMD, however, kinking and fracture of renal artery stents have been reported. Consequently, PTRA alone is the revascularization approach of choice, with the use of stents reserved for the treatment of procedural complications (eg, flow-limiting dissection, arterial rupture).[43]


The rate at which complications of PTRA develop varies among physicians, but potential adverse consequences are known to include thrombosis, vascular or renal perforation, and tearing or dissection of the vessel wall. Restenosis appears to occur in approximately 25% of cases.

Surgical Revascularization

The goal of surgical revascularization is correction of RVHT with preservation of kidney function. However, in older patients with widespread atherosclerotic disease, surgical revascularization poses considerable morbidity and mortality risk; complications include the release of cholesterol emboli during the operation. Consequently, it is reserved primarily for individuals with associated aortic surgical disease and/or failed endovascular repair.[61]  In patients with FMD, the cure rate is as high as 80%, and morbidity is low; however, these results are not significantly better than what can be achieved by means of PTRA with less morbidity, mortality, cost, and inconvenience.[62]

Pharmacologic treatment of RVHT should be provided before the operation in an effort to control blood pressure. Routine chest radiography, electrocardiography (ECG), and, perhaps, echocardiography are important in evaluating the patient’s cardiovascular stability under the stress of hypertension. Abdominal aortography and arteriography are necessary, not only to help establish a diagnosis but also to determine the extent of disease and the approach to surgical intervention.

Postoperative care involves blood pressure monitoring; postoperative medical therapy may be necessary. Postoperative renal scanning or arteriography is also important to identify possible thrombosis, stricture, or any failures in the graft or anastomosis.

Most authors have reported little or no short-term mortality after surgical revascularization.[63, 64, 65] Failure or complications of the procedure may lead to another operation in approximately 27% of cases; usually, the second operation is curative. Date from larger series indicate that graft stenosis may occur about 5% of the time and that thromboses may occur in about 10% of revascularization operations. The various graft materials that may be used are all associated with their own specific complications.



As noted, the goal of therapy for RVHT is to resolve systemic hypertension without compromising renal function. Nephrectomy should be considered a last resort in the treatment of RVHT.

Because renovascular disease is often bilateral, with the contralateral renal system occasionally not affected until years later, it is always best to keep both kidneys functioning whenever possible. However, in cases of severe renal hypoplasia that reduces functional capacity to less than 10% of total renal function, removal of the kidney is the best form of treatment.[66]

Nephrectomy may be necessary if complications arise during surgical revascularization or if the disease is too widespread (especially in segmental arteries) to be effectively bypassed. Children whose hypertension is refractory to the previously mentioned forms of treatment may also need nephrectomy to correct their high blood pressure.[64, 67]


Placing all patients who are hypertensive on a low-salt diet is recommended. In patients with RVHT, this is unlikely to correct the systemic hypertension, but it may assist in managing the hypertension until more definitive therapy can be performed. It certainly does not hurt patients.

In addition, efforts should be made to keep patients well hydrated; dehydration may lead to decreased renal perfusion or increased renin release.


Atherosclerotic RAS is now recognized as an important and fast-growing cause of end-stage renal disease. Because this form of renal failure can be prevented by performing an operation or angioplasty, it is important to identify patients who may be at risk for renal ischemia as a result of atherosclerosis. Even when renal function is impaired, relief of the stenosis, if achieved early enough, may result in dramatic improvement.

Factors that should prompt evaluation for renal artery disease include the following[1, 2] :

  • Onset of hypertension before age 30 years
  • Accelerated, resistant, or malignant hypertension
  • Elevation in serum creatinine of more than 30% after starting an angiotensin- converting enzyme inhibitor or angiotensin-receptor blocker
  • New onset of hypertension after 50 years of age (suggests atherosclerotic renal artery stenosis)
  • Asymmetric kidneys with more than 1.5 cm of difference in the size and otherwise unexplained loss of kidney function
  • Sudden unexplained pulmonary edema
  • Abdominal bruit on physical examination

Deterioration of kidney function in the setting of diffuse atherosclerosis without proteinuria or known renal parenchymal disease, even in the absence of hypertension, is highly suggestive of renovascular disease.


The need for consultation depends on the potential for, development and degree of end-organ damage.  Heart failure likely warrants referral to a cardiologist should be considered; similarly, neurologic symptoms likely warrant referral to a neurologist.

Once a diagnosis of RVHT is made, prompt treatment of the disease is the best protection against further end-organ damage.

Long-Term Monitoring

In addition to diagnosis and treatment of hypertension, kidney function must be assessed and followed so that any dysfunction can be recognized at an early stage, allowing definitive intervention (when appropriate) to be initiated promptly.




Medication Summary

Medical treatment of renovascular hypertension (RVHT) may be necessary to control blood pressure until surgery can be performed. Attempts should be made to reduce the blood pressure before surgery so as to improve the likelihood of a good surgical outcome. Afterward, medical treatment is necessary 25-30% of the time to provide complete resolution of improved or refractory hypertension.

Adrenergic receptor blockers and diuretics are the preferred agents. Arterial dilators are also useful in the preoperative management of malignant hypertension. Calcium channel blockers do not seem to be as widely used, and angiotensin-converting enzyme (ACE) inhibitors are generally avoided because of their potential to compromise renal function.

ACE Inhibitors

Class Summary

ACE inhibitors have been used by some in the control of RVHT. These agents minimize an ischemia-induced rise in angiotensin production. Because hypertension may be dependent on angiotensin II, antihypertensives that inhibit renin or angiotensin II are used widely. All drugs in this class have similar action and adverse effects. In particular, ACE inhibitors increase the risk of decreased renal function. Although this increased risk is usually reversible, the use of these agents is generally avoided until definitive therapy has been attempted.

Renal blood flow is maintained by a balance between angiotensin-II–induced vasoconstriction and prostaglandin-mediated vasodilation. With ACE inhibitors, kidney perfusion is increased and renal vascular resistance decreased. ACE inhibitors induce vasodilation in both afferent and efferent arterioles. The glomerular filtration rate (GFR) generally increases. However, in hypoperfusion states (eg, renal artery stenosis (RAS), aggressive diuresis, and decompensated congestive heart failure), GFR may fall because of unopposed prostaglandin vasodilation.


Captopril, the most commonly used ACE inhibitor, prevents conversion of angiotensin I to angiotensin II (a potent vasoconstrictor), resulting in lower aldosterone secretion. It is excreted primarily by the kidney.

Enalapril (Vasotec)

Enalapril is a competitive ACE inhibitor that reduces angiotensin II levels and decreases aldosterone secretion.

Lisinopril (Zestril, Prinivil)

Lisinopril prevents conversion of angiotensin I to angiotensin II, resulting in decreased aldosterone secretion.

Angiotensin Receptor Blockers (ARBs)

Class Summary

Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system (RAAS) and plays an important role in the pathophysiology of hypertension. Besides being a potent vasoconstrictor, angiotensin II stimulates aldosterone secretion by the adrenal gland; thus, angiotensin receptor blockers (ARBs) decrease systemic vascular resistance without a marked change in heart rate by blocking the effects of angiotensin II.

Type I angiotensin receptors are found in many tissues, including vascular smooth muscle and the adrenal gland. Type II angiotensin receptors also are found in many tissues, although their relationship to cardiovascular hemostasis is not known. The affinity of ARBs for the type I angiotensin receptor is approximately 1000 times greater than that for the type II angiotensin receptor.

In general, ARBs do not inhibit ACE, other hormone receptors, or ion channels. They interfere with the binding of formed angiotensin II to its endogenous receptor. Experience with using ARBs to treat RVHT is still limited. Losartan and valsartan are specific and selective nonpeptide ARBs that block the vasoconstricting and aldosterone-secreting effects of angiotensin II.

Other ARBs have been approved by the US Food and Drug Administration (FDA), including olmesartan (Benicar). Olmesartan is initiated at a dosage of 20 mg/day orally, which may be increased to 40 mg/day after 2 weeks if further blood pressure reduction is required.

Losartan (Cozaar)

Losartan is appropriate for patients unable to tolerate ACE inhibitors. It may induce a more complete inhibition of the RAAS than ACE inhibitors do, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. Compared to the ACE inhibitors (eg, captopril and enalapril), losartan is associated with a lower incidence of drug-induced cough, rash, and taste disturbances.

Valsartan (Diovan)

Valsartan is appropriate for patients unable to tolerate ACE inhibitors. It may induce a more complete inhibition of the RAAS than ACE inhibitors do, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. Compared to the ACE inhibitors (eg, captopril and enalapril), losartan is associated with a lower incidence of drug-induced cough, rash, and taste disturbances.

Blockers, Beta-1 Selective

Class Summary

Adrenergic blockers (both alpha-adrenergic and beta-adrenergic) compete with adrenergic neurotransmitters (eg, catecholamines) for binding at sympathetic receptor sites. They tend to be some of the most effective medicines for prolonged treatment of RVHT.

At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of the alpha-receptor blockers.

Atenolol and metoprolol, in low doses, selectively block beta1 -adrenergic receptors in the heart and vascular smooth muscle. Pharmacodynamic consequences of beta1 -receptor blockade include decreases in (1) resting and exercise heart rate, (2) cardiac output, and (3) systolic and diastolic blood pressure. Like all selective adrenergic antagonists, they lose their selectivity for the beta1 receptor higher doses and can competitively block beta2 -adrenergic receptors in the bronchial and vascular smooth muscles, potentially causing bronchospasm.

Actions that generally make beta blockers useful in treating hypertension include a negative chronotropic effect that decreases the heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the central nervous system (CNS), and suppression of renin release from the kidneys. Thus, beta blockers affect blood pressure via multiple mechanisms.

Metoprolol (Lopressor, Toprol-XL)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.

Atenolol (Tenormin)

Atenolol selectively blocks beta1 receptors, with little or no effect on beta2 types.

Beta-Blockers, Nonselective

Class Summary

Although selective beta1 -blockers (eg, metoprolol) are preferred over nonselective agents in patients with asthma or pulmonary conditions in which acute bronchospasm would put them at risk (eg, chronic obstructive pulmonary disease [COPD], emphysema, or bronchitis), all beta-blockers should be used with caution in these patients, particularly with high-dose therapy.

Propranolol (Inderal, InnoPran XL)

Propranolol is a beta-adrenergic blocking agent. Renin release is enhanced by beta-receptor activation, and chronic beta blockade consistently suppresses plasma renin activity. Propranolol has membrane-stabilizing activity and decreases the automaticity of contractions. It is not suitable for emergency treatment of hypertension and should not be administered IV in hypertensive emergencies.

Labetalol (Trandate)

Labetalol blocks beta1-adrenergic, alpha-adrenergic, and beta2-adrenergic receptor sites.

Alpha Blockers, Antihypertensives

Class Summary

At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of alpha-receptor blockers.


Phentolamine is an alpha1- and alpha2-adrenergic blocking agent that antagonizes the action of circulating epinephrine and norepinephrine, reducing the hypertension that results from catecholamine's effects on the alpha-receptors.

Phenoxybenzamine (Dibenzyline)

Phenoxybenzamine is a noncompetitive alpha-adrenergic blocker. It is a long-acting adrenergic alpha-receptor blocker that can produce and maintain a chemical sympathectomy. Phenoxybenzamine hydrochloride lowers supine and upright blood pressure. It does not affect the parasympathetic nervous system.

Prazosin (Minipress)

Prazosin is an alpha blocker. It decreases arterial tone by allowing peripheral postsynaptic blockade.

Calcium Channel Blockers

Class Summary

Calcium channel blockers provide control of hypertension associated with less impairment of function of the ischemic kidney. It has been suggested that they may have beneficial long-term effects, but this remains uncertain.

Calcium channel blockers inhibit influx of extracellular calcium across both myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged. The resultant decrease in intracellular calcium inhibits the contractile processes of myocardial smooth muscle cells, resulting in dilation of coronary and systemic arteries and improved oxygen delivery to myocardial tissue. In addition, total peripheral resistance, systemic blood pressure, and afterload are decreased.

Diltiazem (Cardizem CD, Dilacor XR, Tiazac)

Diltiazem is similar to verapamil in that it inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes.

Verapamil (Calan, Verelan, Covera-HS)

During depolarization, verapamil inhibits calcium ions from entering slow channels or voltage-sensitive areas of the vascular smooth muscle and myocardium.

Nifedipine (Adalat, Procardia, Procardia XL)

Nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. Sublingual administration is generally safe, despite theoretical concerns.

Diuretics, Other

Class Summary

Diuretics promote excretion of water and electrolytes by the kidneys. They are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites. They may be used as monotherapy or combination therapy to treat hypertension. Thiazide diuretics are preferred.

Diuretics are used only as an adjunct to other medications for RVHT, especially during acute hypertensive crises. Furosemide is especially effective in managing pulmonary edema associated with hypertensive crises and may be particularly useful in patients unresponsive to other diuretics or those who have severe renal impairment.

Furosemide (Lasix)

Furosemide primarily appears to inhibit reabsorption of sodium and chloride in the ascending limb of the loop of Henle. These effects increase urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs after administration of furosemide. Renal vascular resistance decreases, and renal blood flow is enhanced.

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water and potassium and hydrogen ions.


Bumetanide increases excretion of water by interfering with the chloride-binding cotransport system; this, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle. Bumetanide does not appear to act in the distal renal tubule.


Class Summary

Arterial vasodilators are effective in reducing hypertension and may be useful in the short-term management of RVHT before surgical treatment. Nitroprusside is especially useful for this purpose.

Nitroprusside (Nitropress)

Nitroprusside produces vasodilation and increases the inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing the heart rate. It is mainly used when a patient presents with a hypertensive emergency secondary to RVHT.

Cardiovascular, Other

Class Summary

Renin inhibitors constitute the newest class of antihypertensive drugs. They act by disrupting the RAAS feedback loop.

Aliskiren (Tekturna)

Aliskiren is a direct renin inhibitor. It decreases plasma renin activity and inhibits the conversion of angiotensinogen to angiotensin I (thus also decreasing angiotensin II) and thereby disrupts the RAAS feedback loop. Aliskiren is indicated for treatment of hypertension, either alone or in combination with other antihypertensive drugs.


Questions & Answers


What is renovascular hypertension (RVHT)?

What is the role of renovascular hypertension (RVHT) in chronic kidney disease?

What is the pathophysiology of renovascular hypertension (RVHT)?

What are the stages in the pathogenesis of renovascular hypertension (RVHT)?

What is the role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of renovascular hypertension (RVHT)?

What are the manifestations of renovascular hypertension (RVHT)?

What is the pathophysiology of fibromuscular dysplasia in renovascular hypertension (RVHT)?

What is the pathophysiology of midaortic syndrome in renovascular hypertension (RVHT)?

What is the pathophysiology of neurofibromatosis in renovascular hypertension (RVHT)?

What causes renovascular hypertension (RVHT)?

What causes acquired renovascular hypertension (RVHT)?

What is the prevalence of renovascular hypertension (RVHT) in the US?

What is the global prevalence of renovascular hypertension (RVHT)?

Which age groups have the highest prevalence of renovascular hypertension (RVHT)?

What are the sexual predilections of renovascular hypertension (RVHT)?

What are the racial predilections of renovascular hypertension (RVHT)?

What is the prognosis of renovascular hypertension (RVHT)?


What are the signs and symptoms of renovascular hypertension (RVHT)?

What are the clinical risk factors for renovascular hypertension (RVHT)?

Which clinical history findings are characteristic of renovascular hypertension (RVHT)?

Which physical findings are characteristic of renovascular hypertension (RVHT)?

What are the possible complications of renovascular hypertension (RVHT)?

What is the morbidity associated with renovascular hypertension (RVHT)?


Which findings are indications of renovascular hypertension (RVHT) that may progress to serious complications?

Which conditions are included in the differential diagnoses of renovascular hypertension (RVHT)?

What are the differential diagnoses for Renovascular Hypertension?


What are the ACC/AHA guidelines for renal artery stenosis (RAS) screening?

What are the ACC/AHA recommended tests for renovascular hypertension (RVHT) screening?

What is the objective of basic diagnostic testing for pediatric renovascular hypertension (RVHT)?

When should patient transfer be considered for the evaluation of suspected renovascular hypertension (RVHT)?

What is the role of ultrasonography in the workup of renovascular hypertension (RVHT)?

Which lab tests are included in the workup of pediatric renovascular hypertension (RVHT)?

What is the role of renal arteriography in the workup of renovascular hypertension (RVHT)?

What is the role of CT angiography in the workup of renovascular hypertension (RVHT)?

What is the role of magnetic resonance angiography (MRA) in the workup of renovascular hypertension (RVHT)?

What is the role of a renogram in the workup of renovascular hypertension (RVHT)?

What is the role of plasma renin activity (PRA) measurement in the workup of renovascular hypertension (RVHT)?

What is the role of the renal vein renin ratio in the workup of renovascular hypertension (RVHT)?

What is the role of carbon dioxide angiography in the workup of renovascular hypertension (RVHT)?


How is renovascular hypertension (RVHT) treated?

Which medications are used in the treatment of renovascular hypertension (RVHT)?

What is the role of PTRA in the treatment of renovascular hypertension (RVHT)?

What is the role of renal stents in the treatment of renovascular hypertension (RVHT)?

What are the possible complications of PTRA for the treatment of renovascular hypertension (RVHT)?

What is the role of surgical revascularization in the treatment of renovascular hypertension (RVHT)?

What is included in preoperative care prior to surgical revascularization for renovascular hypertension (RVHT)?

What is included in postoperative care following surgical revascularization for the treatment of renovascular hypertension (RVHT)?

What are the possible complications of surgical revascularization for the treatment of renovascular hypertension (RVHT)?

What is the role of nephrectomy in the treatment of renovascular hypertension (RVHT)?

Which dietary modifications are used in the treatment of renovascular hypertension (RVHT)?

How is RAS prevented in patients with renovascular hypertension (RVHT)?

Which specialist consultations are beneficial to patients with renovascular hypertension (RVHT)?

What is included in the long-term monitoring of renovascular hypertension (RVHT)?


What is the role of medications in the treatment of renovascular hypertension (RVHT)?

Which medications in the drug class Cardiovascular, Other are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Vasodilators are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Diuretics, Other are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Calcium Channel Blockers are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Alpha Blockers, Antihypertensives are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Beta-Blockers, Nonselective are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Blockers, Beta-1 Selective are used in the treatment of Renovascular Hypertension?

Which medications in the drug class Angiotensin Receptor Blockers (ARBs) are used in the treatment of Renovascular Hypertension?

Which medications in the drug class ACE Inhibitors are used in the treatment of Renovascular Hypertension?