eMedicine Specialties > Nephrology > Hypertension and the Kidney

Renovascular Hypertension

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Sandeep S Soman, MBBS, MD, DNB, Senior Staff Physician, Department of Internal Medicine, Division of Nephrology and Hypertension, Henry Ford Hospital

Updated: Sep 4, 2009

Introduction

Background

Renovascular hypertension (RVHT) denotes the causal relationship 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. More specific diagnoses are made retrospectively when hypertension is improved after intravascular intervention. (See image below and Image 1.)

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

In the setting of 2 kidneys, 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; hence, volume plays an additive role in the hypertension.

Pathophysiology

The chief pathophysiologic mechanism underlying RVHT involves activation of both limbs of the renin-angiotensin-aldosterone system and depends on the presence or absence of a contralateral kidney. 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 2-kidney 1-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 1-kidney 1-clip model), sodium and water handling is compromised, sodium and water retention ensues, and volume-mediated hypertension occurs.

In unilateral renal artery stenosis (RAS), renin production is increased by the ischemic kidney but suppressed in the unaffected nonstenotic kidney, which lacks the same ischemic stimulus. Consequently, when 2 kidneys are present with a unilateral stenosis (2-kidney 1-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 (ie, of excess sodium and water) 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 pathophysiologic scheme for RVHT is presented in the image below and in Image 2.

Proposed pathogenesis of renovascular hypertension.

Stages in the development of renovascular hypertension

The evolution of RVHT has been described as having 3 stages. 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 2 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 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 angiotensin II-dependent 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 2 stages and renal perfusion is reinstated, blood pressure soon returns to a normal level. If renal hypoperfusion persists and stage 3 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 stage, 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.

The renin-angiotensin system and control of intrarenal hemodynamics in renovascular hypertension

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 that of the afferent side. 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 renin-angiotensin system, 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. Note that an acute decline in renal function in this setting is reversible once the ACE inhibitor or the angiotensin receptor blocking agent is discontinued.

The propensity for angiotensin receptor blocking agents to adversely affect GFR is based on similar pathophysiology.

Classification

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 involves the distal two thirds and branches of the renal arteries and is most common among younger women.

Frequency

United States

RVHT is the most common type of secondary hypertension, accounting for 1-5% of cases in unselected populations and as many as 30% of cases in selected populations. The prevalence may be up to 60% in patients older than 70 years.

International

The prevalence of RVHT internationally is not clear, but it likely accounts for the sole etiology in a similarly small percentage (<1% in the United States) of unselected patients with hypertension.

Mortality/Morbidity

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.

Race

RVHT and RAS, in particular, are less common among the black population than the white population.

Sex

RVHT is most common in younger women and older men. Younger women develop RVHT most commonly from fibromuscular dysplasia 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.

Age

The onset of RVHT tends to occur in patients younger than 30 years or older than 50 years.

Clinical

History

• Onset of hypertension occurring in patients younger than 30 years without risk factors
• Abrupt onset of severe (stage II) hypertension (greater than 160/100 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 RAS
• Negative family history for hypertension
• Smoking tobacco products
• Acute sustained rise in serum creatinine levels with ACE inhibition
• Unprovoked hypokalemia (serum potassium level <3.6 mEq/L, often associated with metabolic alkalosis)
• Symptoms of atherosclerotic disease elsewhere 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, asymmetric kidneys of greater than 1.5 cm difference or diffuse atherosclerosis

Physical

• Recurrent flash pulmonary edema or unexplained episodes of congestive heart failure
• Advanced funduscopic changes
• Abdominal bruit
  • A clear abdominal bruit is heard in 46% of patients with RVHT.
  • It also is heard in 9% of patients with essential hypertension; however, innocent bruits are common in younger individuals.
  • Systolic-diastolic bruits in combination with hypertension are suggestive of RVHT.

Causes

• Overall, approximately two thirds of RVHT cases are caused by atherosclerotic disease and one third are caused by fibromuscular dysplasia or other congenital disorders.
• Other clinical entities that may be associated with RVHT include cholesterol embolic disease, acute arterial thrombosis or embolism, aortic dissection, renal arterial trauma, arterial aneurysm, arteriovenous malformation of the renal artery, and polyarteritis nodosa.

Differential Diagnoses

Hypertension

Other Problems to Be Considered

Other nonessential forms of hypertension
Essential hypertension

Workup

Laboratory Studies

• Characterizing the clinical risks for RVHT before embarking on an extensive workup that may not be productive or cost effective is useful. Patients in whom a definite noninvasive or invasive workup is indicated are those with the clinical features described in History and Physical. 
• A schematic approach to the diagnostic investigation of RAS is shown in the image below and in Image 3.

Diagnostic flowchart for the workup of renal artery stenosis.

• The criterion standard to establish a diagnosis of RAS is renal arteriography.  The lab studies are mentioned for historical background but are no longer universally considered useful as screening tests.
• Plasma renin activity  
• The baseline plasma renin activity (PRA) is elevated in 50-80% of patients with RVHT. 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 PRA. 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, diuretics), the low sensitivity, and the somewhat decreased predictive value when compared to a renogram after ACE inhibition.
• Renal vein renin measurements  
• Renal vein renin measurements compare renin release from each kidney and are used to predict the potential success of surgical revascularization. Increased renin secretion in the ischemic kidney as compared to the contralateral kidney, that is, a renal vein renin difference of 1.5-fold, constitutes a positive test result and suggests that revascularization will treat elevated blood pressure successfully. Renin secretion in the contralateral kidney is suppressed, as evidenced by the similar levels of renin measured in the renal artery (infrarenal inferior vena cava) and renal vein.
• Fewer than 10% of healthy patients have a ratio above 1.5 and fewer than 20% have a ratio below 1.1. The accuracy of these measurements has been suggested to be enhanced by the prior administration of an ACE inhibitor, which will increase renin secretion on the affected side.
• False-negative and false-positive results are common. Although more than 90% of patients with unilateral RAS and lateralizing renin values have a positive response to angioplasty or surgery, approximately 50% with nonlateralizing findings also benefit from correction of the stenosis. As a result, most physicians rely on the clinical index of suspicion rather than 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 renins can be used to determine the side that most contributes to the hypertension.
• Screening: Guidelines of the AmericanCollege of Cardiology and the American Heart Association advocate screening for RAS only for patients in whom a corrective procedure would be considered if renovascular disease was detected.

Imaging Studies

• Angiography  
• A conventional renal angiogram or an intra-arterial digital subtraction angiogram (DSA) remains the diagnostic criterion standard among available tests for detecting renal artery occlusive disease. Because intra-arterial DSA requires less radiocontrast (25-50 mL) than conventional angiography (100 mL), it is preferred for patients with compromised renal function. A RAS of greater than or equal to 70% or a stenosis of 50% with poststenotic dilatation is considered hemodynamically significant.
• Intravenous DSA is less invasive but requires more radiocontrast than intra-arterial DSA. Its sensitivity and specificity are 90% or less as compared to arterial studies; hence, it is no longer used.
• Carbon dioxide digital angiography is used as an effective alternative to iodinated radiocontrast material in patients with renal insufficiency. Carbon dioxide angiogram allows a gross assessment of the presence of a stenotic lesion. Angioplasty and/or surgical intervention require subsequent traditional radiocontrast angiography to specifically outline the lesions; however, with carbon dioxide angiography, patients can be identified without the risk of dye-related renal injury.
• Magnetic resonance angiography
• Magnetic resonance angiography (MRA)¹ is increasingly reported to provide better results than the noninvasive screening procedures mentioned in Lab Studies.  Studies indicate that 3-dimensional MRA with gadolinium-based contrast agents² (which have potential for nephrotoxicity) has a sensitivity of 96-100% and a specificity of 71-96% for the detection of a main RAS of greater than 50%.
• When combined with cardiac synchronization, 3-dimensional MRA can sharply delineate the entire length of the major renal arteries (see image below and Image 1); however, MRA remains suboptimal for the detection of hemodynamically significant lesions of distal, intrarenal, and accessory renal arteries, which, for all purposes, behave pathophysiologically as RAS, and it is also of limited value in fibromuscular dysplasia, where lesions, by being primarily middle and distal, are less well visualized by MRA.
  
  Correlations between MRA and digital subtraction angiography are reported to exceed 90% for accuracy, sensitivity, and specificity. However, the use of gadolinium as an enhancing agent in MR procedures has been linked to the development of nephrogenic systemic fibrosis in patients with poor renal function. Hence, MRA is an attractive alternative only for patients without renal disease who are not at risk for contrast injury.

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

• Limitations include cost and technique availability. Contraindications to MRA include reduced renal function (estimated GFR <30 mL/min), claustrophobia, and patients with a metallic implant, such as a pacemaker or surgical clip. The risk-benefit ratio should be carefully considered in patients with moderately reduced renal function (estimated GFR 30-60 mL/min).
• Spiral CT scan with angiography  
• SpiralCT scans using small amounts of IV contrast (ie, CT angiography) offer the diagnostic accuracy of arteriography and the lower risk of renal injury with IV digital subtraction angiography.
• Sensitivity and specificity of the spiral CT scan for detecting RAS are approximately 98% and 94%, respectively. In patients with a plasma creatinine concentration higher than 1.7 mg/dL (150 µmol/L), the accuracy is lower (93% sensitivity, 81% specificity), possibly due to reduced renal blood flow.
• Doppler ultrasonography  
• Doppler ultrasonography provides both anatomical 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 the detection of RAS exceeding 70%. Doppler ultrasonographic evaluation of renal resistance indices (1-end diastolic velocity/maximum systolic velocity X 100) can be used to classify patients as potential responders or nonresponders to intervention (ie, a renal resistance index exceeding 80% infers a low likelihood that correction of the stenosis will eventuate in improved blood pressure control or renal function).
• 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.
• Important disadvantages of this modality include the potential 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 (requires approximately 2 h) and is a technically difficult procedure with a steep learning curve, making success highly operator dependent.
• A promising screening test, intrarenal echo Doppler velocimetric indices, is currently under investigation.
• Renogram and captopril renogram  
• 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. 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.
• 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 when assessing treatment options. The latter may be more reliable in patients with renal insufficiency.
• Positive results from ACE inhibitor renogram are determined by the following 2 criteria: (1) decreased relative uptake of isotope, with 1 kidney accounting for less than 40% of the total GFR and (2) delayed peak uptake of the isotope of more than 10-11 minutes (normal is 3-6 min).
• Note that a slower washout of the isotope may occur in the stenotic kidney, which is 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.

Other Tests

• The IV pyelogram is mentioned as a test of historical significance. It has a sensitivity of only 75-80%; thus, a negative test result cannot exclude RVHT reliably. Furthermore, bilateral disease can be missed if a small difference exists between the 2 kidneys. Major findings on IV pyelography that suggest the presence of unilateral ischemia include decreased renal size and delayed caliceal appearance time when compared to the contralateral kidney.
• Selecting the appropriate test
  • At present, no sufficiently accurate, noninvasive, radiologic, or serologic screening test is available that, if negative, completely excludes the presence of RAS. Therefore, clinical index of suspicion remains the primary determinant for the degree of evaluation (see image below and Image 3).

Diagnostic flowchart for the workup of renal artery stenosis.

• When the history is highly suggestive and no risk for radiocontrast-mediated renal injury is present, an intra-arterial DSA or conventional angiogram (criterion standard) is the appropriate initial test. In patients at risk, a carbon dioxide angiogram can determine the presence of a stenosis, and the risk of radiocontrast angiogram is imposed only on those individuals most likely to benefit.
• Perform a spiral CT scan, MRA, or duplex ultrasonography (depending on availability and local experience) when moderate suspicion of renovascular disease exists. A negative test result indicates that RAS is highly unlikely, while a positive test result can be followed by renal arteriography.

Treatment

Medical Care

• 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 key.
• 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.
• 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 renal 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. Intervention of 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.³ Thus, the superiority of surgical intervention versus medical intervention (or vice versa) remains unproven.
• Percutaneous transluminal renal angioplasty
  • Percutaneous transluminal angioplasty (PTRA) is a nonsurgical procedure used to open stenotic renal arteries, the most amenable lesions being those without total occlusion. Outcomes in patients with lesions resulting from fibromuscular dysplasia appear to be significantly better than they are in persons whose lesions are associated with atherosclerotic stenosis, with cure reported in 50-85% of patients in the former group, and in 8-20% of persons in the latter group.
    
    Restenosis requiring repeat angioplasty was reported in fewer than 10% of patients with fibromuscular disease and in 8-30% of those with atherosclerotic stenosis. Improvement in blood pressure control with fewer antihypertensive medications was achieved in 30-35% and 50-60% of patients with fibromuscular or atherosclerotic lesions, respectively.
  • A Swedish study of 105 patients treated with PTRA reported a 5-year survival rate of 83% for patients with arteriosclerotic renovascular disease.⁴  The rate for patients with fibromuscular vascular disease was even higher, reaching 100%.
  • The poor results observed in patients with bilateral renal artery disease suggest that surgical intervention should be a strong consideration in this setting.
  • Intravascular stents placed during angioplasty may be helpful in the prevention of restenosis and the management of RVHT. Current 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, such as dissection (see images below and Images 4-6). Primary renal artery stenting in patients with atherosclerotic RAS has a high technical success rate and a low complication rate.^5,6
  • In patients with diffuse atherosclerosis, the complication rate with either surgery or angioplasty is relatively high. Medical therapy may be preferred.

Angiogram showing bilateral renal artery stenosis. Courtesy of Department of Radiology, Henry Ford Hospital.

After percutaneous transluminal angioplasty (right renal artery). Courtesy of Department of Radiology, Henry Ford Hospital.

After percutaneous transluminal angioplasty and stent placement (left renal artery). Courtesy of Department of Radiology, Henry Ford Hospital.

Surgical Care

• Surgical revascularization
  • The underlying diagnosis is the major determinant of the results of this surgery. As more patients with advanced atherosclerosis in multiple vessels are brought to surgery, performing various bypass procedures may become less feasible because of the following: (1) the certainty that the RAS is the cause of the hypertension is less, and (2) the prognosis may be determined by the extent of atherosclerosis elsewhere in the body.
  • Another potential problem is the release of cholesterol emboli during the operation; however, 80-90% of patients undergoing operation for atherosclerotic RVHT benefit (cure or improvement), with a perioperative mortality rate of less than 5%.
  • In patients with fibromuscular dysplasia, the cure rate is as high as 80% and morbidity is low; however, these results are not significantly better than what can be achieved with renal angioplasty, at less morbidity, mortality, cost, and inconvenience.
• In patients with diffuse atherosclerosis, the complication rate with both surgery and angioplasty is relatively high.

Medication

All classes of antihypertensive medications are used to treat RVHT; however, the most effective therapy is with an ACE inhibitor, which minimizes the ischemia-induced rise in angiotensin production. Because hypertension may be dependent on angiotensin II, antihypertensives that inhibit renin or angiotensin II are used widely. An ACE inhibitor markedly decreases blood flow through the stenotic kidney; thus, in patients with a solitary kidney or bilateral renovascular disease, blood pressure may fall rapidly, with an ensuing deterioration in renal function. This usually is reversible upon discontinuation of the medication.

Although less clinical experience exists with newer angiotensin receptor blockers (ARBs), they appear to be as effective as ACE inhibitors in experimental models. In patients without hemodynamically significant renal artery disease, an increase in serum creatinine level of up to 35% above baseline with an ACE or 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 ACE inhibitors. Diuretics enhance sodium and water diuresis, thereby eliminating the volume-mediated component of RVHT. Calcium channel blockers (CCBs) may provide equally good control of hypertension, with presumably less impairment in function of the ischemic kidney than ACE inhibitors.

A selective aldosterone inhibitor, eplerenone (INSPRA) is now available for the treatment of hypertension. It selectively blocks aldosterone at the mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels, brain) tissues, thus decreasing blood pressure and sodium reabsorption. The adult dose is 50 mg PO qd and it may be increased after 4 wk, not to exceed 100 mg/d. Contraindications include documented hypersensitivity, hyperkalemia, coadministration with drugs causing increased potassium, type 2 diabetes with microalbuminuria, and moderate-to-severe renal insufficiency (ie, CrCl <50 mL/min or serum creatinine >2 mg/dL [males] or >1.8 mg/dL [females]). Eplerenone is a CYP450 3A4 substrate, thus potent CYP3A4 inhibitors (eg, ketoconazole) increase serum levels about 5-fold, whereas less potent CYP3A4 inhibitors (eg, erythromycin, saquinavir, verapamil, fluconazole) increase serum levels about 2-fold. Grapefruit juice increases serum levels about 25%.

Coadministration with potassium supplements, salt substitutes, or drugs known to increase serum potassium (eg, amiloride, spironolactone, triamterene, ACE inhibitors, angiotensin II inhibitors) increases risk of hyperkalemia. Eplerenone may cause hyperkalemia, headache, or dizziness. Caution is advised with hepatic insufficiency.

Angiotensin-converting enzyme inhibitors

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.

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Excreted primarily by the kidney.

Dosing

Adult

25-75 mg PO tid

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics

Contraindications

Documented hypersensitivity; previous history of angioedema or anaphylaxis with ACE inhibitors; hyperkalemia; bilateral RAS; solitary kidney with RAS; pregnancy, due to risk of fetal hypotension; anuria; renal failure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe congestive heart failure (CHF); adverse effects include severe hypotension, acute renal failure (especially in bilateral RAS), hyperkalemia, dry cough sometimes accompanied by wheezing, and angioedema; cough and angioedema are believed to be mediated by bradykinin

Enalapril (Vasotec)

Competitive inhibitor of ACE. Reduces angiotensin II levels and decreases aldosterone secretion.

Dosing

Adult

10-20 mg PO qd or divided bid

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe CHF

Lisinopril (Zestril, Prinivil)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Dosing

Adult

10-80 mg PO qd

Pediatric

Not established

Interactions

May increase digoxin, lithium, and allopurinol levels; probenecid may increase levels; coadministration with diuretics increases hypotensive effects; hypotensive effects may be enhanced when administered concurrently with diuretics and NSAIDs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe CHF

Angiotensin receptor blockers

Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system 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, ARBs decrease systemic vascular resistance without a marked change in heart rate by blocking the effects of angiotensin II. Type 1 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 is approximately 1000-fold greater for the type I angiotensin receptor than for the type II angiotensin receptor.

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

Other ARBs have been approved by the FDA, including olmesartan (Benicar). Olmesartan is initiated at 20 mg PO qd and may be increased to 40 mg/d after 2 wk if further BP reduction is required.

Losartan (Cozaar)

For patients unable to tolerate ACE inhibitors. May induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Compared to the ACE inhibitors (eg, captopril, enalapril), losartan is associated with lower incidence of drug-induced cough, rash, and taste disturbances.

Dosing

Adult

Initial: 50 mg/d PO
Maintenance: 25-100 mg/d PO

Pediatric

Not established

Interactions

Enhances hypotensive effects of antihypertensive agents or diuretics if administered concomitantly; use with potassium-sparing diuretics, potassium salts, or salt substitutes containing potassium may lead to increases in serum potassium; ketoconazole, sulfaphenazole, and phenobarbital may decrease effects; cimetidine and monoxidine may increase effects

Contraindications

Documented hypersensitivity; do not use during second or third trimester of pregnancy (pregnancy category D); bilateral RAS or solitary kidney with unilateral RAS; breastfeeding not recommended during ARB therapy because of potential adverse effects in the infant

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperkalemia, suspected bilateral RAS, or solitary kidney with unilateral RAS

Valsartan (Diovan)

For patients unable to tolerate ACE inhibitors. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors. Does not affect response to bradykinin and is less likely to be associated with cough and angioedema. Compared with ACE inhibitors (eg, captopril, enalapril), it is associated with lower incidence of drug-induced cough, rash, and taste disturbances.

Dosing

Adult

Initial: 80 mg PO qd unless volume depleted
Maintenance: 80-320 mg PO qd

Pediatric

Not established

Interactions

Ketoconazole, troleandomycin, sulfaphenazole, and phenobarbital may decrease effects; cimetidine and monoxidine may increase effects

Contraindications

Documented hypersensitivity; severe hepatic insufficiency; biliary cirrhosis or obstruction; primary hyperaldosteronism; bilateral RAS

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperkalemia, suspected bilateral RAS, or solitary kidney with unilateral RAS

Beta-adrenergic blocking agents

Compete with adrenergic neurotransmitters (eg, catecholamines) for binding at sympathetic receptor sites. 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 a decrease in both resting and exercise heart rate and cardiac output and a decrease in both systolic and diastolic blood pressure. As with all selective adrenergic antagonists, selectivity for the beta1-receptor is lost at higher doses, and they 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, a reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Thus, beta-blockers affect blood pressure via multiple mechanisms.

Metoprolol (Lopressor)

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

Dosing

Adult

100-400 mg/d PO divided bid

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, CCBs, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated CHF; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Atenolol (Tenormin)

Selectively blocks beta1-receptors with little or no effect on beta2 types.

Dosing

Adult

50 mg PO qd; increase to 100 mg/d if necessary

Pediatric

50-100 mg/d PO qd

Interactions

Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity

Contraindications

Documented hypersensitivity; CHF; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without a pacemaker)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG; relatively contraindicated in severe hepatic disease; caution in poorly controlled diabetes mellitus, particularly brittle diabetes; can prolong or enhance hypoglycemia by interfering with glycogenolysis; can mask signs of hypoglycemia, especially tachycardia, palpitations, and tremors; can occasionally cause hyperglycemia, thought to be due to blockade of beta2-receptors on pancreatic islet cells, which would inhibit insulin secretion

Propranolol (Inderal, Betachron)

Although beta1 selective beta-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, COPD, emphysema, or bronchitis), all beta-blockers should be used with caution in these patients, particularly with high-dose therapy. Has membrane-stabilizing activity and decreases automaticity of contractions. Not suitable for emergency treatment of hypertension. Do not administer IV in hypertensive emergencies.

Dosing

Adult

40-80 mg PO bid initial; increase to 160-320 mg/d (some patients require up to 640 mg/d)

Pediatric

Not established

Interactions

Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; CCBs, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase

Contraindications

Documented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt discontinuation can result in development of myocardial ischemia, infarction, ventricular arrhythmias, or severe hypertension, particularly in patients with preexisting cardiac disease; caution in hyperthyroidism or thyrotoxicosis because drug can mask tachycardia resulting from this condition; abrupt withdrawal in a patient with hyperthyroidism can precipitate a thyroid storm; patients with severe bradycardia or advanced AV block; do not use in patients with cardiogenic shock or systolic CHF, particularly in those with severely compromised left ventricular dysfunction, because the negative inotropic effect of these drugs can further depress cardiac output; relatively contraindicated in patients with Raynaud disease or peripheral vascular disease because reduced cardiac output and relative increase in alpha stimulation can exacerbate symptoms

Calcium channel blockers

These agents provide control of hypertension associated with less impairment of function of the ischemic kidney. Suggested that they may have beneficial long-term effects, but this remains uncertain.

Diltiazem (Cardizem CD, Dilacor)

CCBs inhibit influx of extracellular calcium across both myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged.
Resultant decrease in intracellular calcium inhibits 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.
Similar to verapamil in that it inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes.

Dosing

Adult

30-80 mg PO q6h (qd if using long-acting form)

Pediatric

Not established

Interactions

May increase carbamazepine, digoxin, cyclosporine, and theophylline levels; when administered with amiodarone may cause bradycardia and a decrease in cardiac output; when administered with beta-blockers may increase cardiac depression; cimetidine may increase levels

Contraindications

Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in ventricular dysfunction, severe bradycardia, cardiogenic shock, CHF, and patients taking beta-adrenergic blocking agents (can precipitate or exacerbate heart failure or cause excessive bradycardia or cardiac conduction abnormalities); do not use in acute MI and associated left ventricular dysfunction; decreases peripheral resistance and can worsen hypotension; due to inhibitory effects on AV node conduction, do not use in patients with preexisting second-degree or third-degree AV block or previous conduction abnormalities; can worsen abnormal pressure gradient associated with advanced aortic stenosis; caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur; caution in patients with sinoatrial nodal dysfunction (eg, sick sinus syndrome)

Verapamil (Calan)

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

Dosing

Adult

80-160 mg PO q8h
75-150 mcg/kg IV

Pediatric

Not established

Interactions

May increase carbamazepine, digoxin, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and a decrease in cardiac output; when administered concurrently with beta-blockers may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels

Contraindications

Documented hypersensitivity; severe CHF; sick sinus syndrome or second-degree or third-degree AV block; hypotension (<90 mm Hg systolic)

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatocellular injury may occur; transient elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have occurred (elevations have been transient and may disappear with continued treatment); monitor liver function periodically

Nifedipine (Adalat, Procardia)

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

Dosing

Adult

20-40 mg PO q8h

Pediatric

Not established

Interactions

Caution with coadministration of any agent that can lower BP, including beta-blockers and opioids; H2 blockers (eg, cimetidine) may increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause lower extremity edema; allergic hepatitis has occurred but is rare

Diuretics

Used only as an adjunct to other medications for RVHT, especially during acute hypertensive crisis. 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)

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 following administration of furosemide. Renal vascular resistance decreases and renal blood flow is enhanced.

Dosing

Adult

20-80 mg PO qd/tid

Pediatric

Not established

Interactions

Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently

Contraindications

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Hydrochlorothiazide (Esidrix, Microzide, HydroDIURIL)

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

Dosing

Adult

25-100 mg PO qd

Pediatric

Not established

Interactions

Thiazides may decrease effects of anticoagulants, antigout agents, and sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity; anuria; renal decompensation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal disease, hepatic disease, gout, diabetes mellitus, and erythematosus

Bumetanide (Bumex)

Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle. Does not appear to act in the distal renal tubule.

Dosing

Adult

0.5-2 mg PO qd or divided bid

Pediatric

Not established

Interactions

Decreases effects of indomethacin and probenecid; may increase lithium toxicity

Contraindications

Documented hypersensitivity; anuria; increasing azotemia

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Profound diuresis with fluid and electrolyte loss may occur; caution in hepatic failure

Vasodilators

These agents are effective in reducing hypertension.

Nitroprusside (Nitropress)

Mainly used when patient presents with a hypertensive emergency secondary to RVHT. See Hypertension and Hypertensive Emergencies.

Dosing

Adult

0.5-10 mcg/kg/min IV

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; subaortic stenosis, idiopathic hypertrophic; atrial fibrillation or flutter

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Most serious toxicity is related to accumulation of cyanide, metabolic acidosis, arrhythmias, and excessive hypotension, which may, in turn, cause death; patients with congenital optic atrophy (Leber disease) or toxic amblyopia are deficient in enzyme rhodanese, crucial for metabolism of nitroprusside (patients are at increased risk of developing cyanide toxicity while receiving nitroprusside therapy); watch for thiocyanate toxicity, especially with renal impairment; caution in pulmonary disease (may aggravate preexisting hypoxemia); administer only in setting where adequate equipment and personnel are available to monitor blood pressure closely (may cause severe hypotension); can cause increase in intracranial pressure (relatively contraindicated in preexisting increased intracranial pressure, including encephalopathy)

Renin inhibitor

Newest class of antihypertensive drugs. Acts by disrupting the renin-angiotensin-aldosterone system feedback loop.

Aliskiren (Tekturna)

Direct renin inhibitor. Decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I (as a result, also decreasing angiotensin II) and, thereby, disrupts the renin-angiotensin-aldosterone system (RAAS) feedback loop. Indicated for hypertension as monotherapy or in combination with other antihypertensive drugs.

Dosing

Adult

150 mg PO qd initially; if needed, may increase to 300 mg/d

Pediatric

<18 years: Not established

Interactions

Coadministration with irbesartan decreases C_max by 50%; coadministration with atorvastatin increases C_max and AUC by 50%; ketoconazole increases plasma levels by about 80%; does not inhibit CYP450 isoenzymes or induce CYP3A4; coadministration with furosemide decreases furosemide C_max and AUC by 30% and 50%, respectively; high-fat meals substantially decrease absorption; use with maximal dose of ACE inhibitors has not been studied

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Discontinue use in pregnancy as soon as possible because use of drugs affecting the renin-angiotensin system during second and third trimesters has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, renal failure, and fetal death; may cause angioedema; dose-related GI adverse effects may occur

Follow-up

Further Inpatient Care

• 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.

Further Outpatient Care

• In addition to diagnosis and treatment of hypertension, renal function must be assessed and followed so that recognition of renal dysfunction is early and definitive intervention, when appropriate, can be instituted.

Transfer

• The patient should be transferred to another facility when necessary testing to confirm or refute the diagnosis of RVHT or to assess the severity of a confirmed diagnosis of RVHT cannot be performed adequately at the current treating facility.
• Additionally, the patient should be transferred to a tertiary care medical facility when necessary surgical treatments, such as renal artery bypass or renal artery transluminal angioplasty, must be performed and the current treating facility is not equipped for such procedures.

Deterrence/Prevention

• Renal arterial atherosclerotic stenosis now is recognized as an important and fastest-growing cause of end-stage renal disease. Because preventing this form of renal failure is possible by performing an operation or angioplasty, identifying patients who may be at risk for renal ischemia by atherosclerosis is important. Even when renal function is impaired, relief of the stenosis, if achieved early enough, may result in dramatic improvement.
• A clinically atypical course of hypertension developing in people older than 50 years, difficulty controlling long-standing hypertension that previously was easy to control, or an increase in creatinine level after administration of an ACE inhibitor all should prompt evaluation for renal arterial disease.
• Deterioration of renal function in the setting of diffuse atherosclerosis but no proteinuria or known renal parenchymal disease, even in the absence of hypertension, is highly suggestive of renovascular disease.

Complications

• Major complications of RVHT include end-organ damage from chronically uncontrolled hypertension and progressive renal failure, an important and indolent sequela of chronic renal ischemia.

Prognosis

• 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 and/or angioplasty.
• RVHT in the setting of chronic renal ischemia and consequent renal dysfunction has been linked to worse outcomes.

Patient Education

• Education about hypertension should include information about the clinical features associated with RVHT (see Clinical) and information about the importance of good blood pressure control.

Miscellaneous

Medicolegal Pitfalls

• Failure to recognize clues to the presence of RVHT that might lead to complications, such as stroke, renal failure, and cardiac decompensation
  • 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 signifying the evolution of ischemic nephropathy

Multimedia

Media file 1: Magnetic resonance angiography (MRA) showing renal artery stenosis. Courtesy of Patricia Stoltzfus, MD, Chief of Interventional Radiology, West Virginia University.

Media file 2: Proposed pathogenesis of renovascular hypertension.

Media file 3: Diagnostic flowchart for the workup of renal artery stenosis.

Media file 4: Angiogram showing bilateral renal artery stenosis. Courtesy of Department of Radiology, Henry Ford Hospital.

Media file 5: After percutaneous transluminal angioplasty (right renal artery). Courtesy of Department of Radiology, Henry Ford Hospital.

Media file 6: After percutaneous transluminal angioplasty and stent placement (left renal artery). Courtesy of Department of Radiology, Henry Ford Hospital.

Media file 7: Close-up of the Palmaz stent. Courtesy of Department of Radiology, Henry Ford Hospital.

References

1. Slanina M, Zizka J, Klzo L, et al. Contrast-enhanced MR angiography utilizing parallel acquisition techniques in renal artery stenosis detection. Eur J Radiol. Aug 9 2009;[Medline].

2. Nchimi A, Brisbois D, Materne R, et al. Free-breathing accelerated gadolinium-enhanced MR angiography in the diagnosis of renovascular disease. AJR Am J Roentgenol. Jun 2009;192(6):1531-7. [Medline].

3. Textor SC, Lerman L, McKusick M. The uncertain value of renal artery interventions: where are we now?. JACC Cardiovasc Interv. Mar 2009;2(3):175-82. [Medline].

4. Jensen G, Annerstedt M, Klingenstierna H, et al. Survival and quality of life after renal angioplasty: a five-year follow-up study. Scand J Urol Nephrol. 2009;43(3):236-41. [Medline].

5. Jokhi PP, Ramanathan K, Walsh S, et al. Experience of stenting for atherosclerotic renal artery stenosis in a cardiac catheterization laboratory: technical considerations and complications. Can J Cardiol. Aug 2009;25(8):e273-8. [Medline].

6. Leesar MA, Varma J, Shapira A, et al. Prediction of hypertension improvement after stenting of renal artery stenosis: comparative accuracy of translesional pressure gradients, intravascular ultrasound, and angiography. J Am Coll Cardiol. Jun 23 2009;53(25):2363-71. [Medline].

7. Aurell M, Jensen G. Treatment of renovascular hypertension. Nephron. 1997;75(4):373-83. [Medline].

8. Bloch MJ, Basile J. Clinical insights into the diagnosis and management of renovascular disease. An evidence-based review. Minerva Med. Oct 2004;95(5):357-73. [Medline].

9. Bloch MJ, Basile J. The diagnosis and management of renovascular disease: a primary care perspective. Part I. Making the diagnosis. J Clin Hypertens (Greenwich). May-Jun 2003;5(3):210-8. [Medline].

10. Bloch MJ, Basile J. The diagnosis and management of renovascular disease: a primary care perspective. Part II. Issues in management. J Clin Hypertens (Greenwich). Jul-Aug 2003;5(4):261-8. [Medline].

11. Canzanello VJ, Textor SC. Noninvasive diagnosis of renovascular disease. Mayo Clin Proc. Dec 1994;69(12):1172-81. [Medline].

12. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. May 21 2003;289(19):2560-72. [Medline].

13. Conlon PJ, O'Riordan E, Kalra PA. New insights into the epidemiologic and clinical manifestations of atherosclerotic renovascular disease. Am J Kidney Dis. Apr 2000;35(4):573-87. [Medline].

14. Greco BA, Breyer JA. Atherosclerotic ischemic renal disease. Am J Kidney Dis. Feb 1997;29(2):167-87. [Medline].

15. Hacklander T, Mertens H, Stattaus J, Lurken M, Lerch H, Altenburg A, et al. Evaluation of renovascular hypertension: comparison of functional MRI and contrast-enhanced MRA with a routinely performed renal scintigraphy and DSA. J Comput Assist Tomogr. Nov-Dec 2004;28(6):823-31. [Medline].

16. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. Mar 21 2006;113(11):e463-654. [Medline]. [Full Text].

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18. Leung DA, Hoffmann U, Pfammatter T, Hany TF, Rainoni L, Hilfiker P, et al. Magnetic resonance angiography versus duplex sonography for diagnosing renovascular disease. Hypertension. Feb 1999;33(2):726-31. [Medline].

19. Ploth DW. Renovascular hypertension. In: Jacobson H, Striker G, Klahr S, eds. The Principles and Practice of Nephrology. 2^nd ed. Philadelphia: BC Decker; 1995:379-86.

20. Rabbia C, Valpreda S. Duplex scan sonography of renal artery stenosis. Int Angiol. Jun 2003;22(2):101-15. [Medline].

21. Radermacher J, Haller H. The right diagnostic work-up: investigating renal and renovascular disorders. J Hypertens Suppl. May 2003;21 Suppl 2:S19-24. [Medline].

22. Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med. Feb 8 2001;344(6):431-42. [Medline].

23. Soulez G, Oliva VL, Turpin S, Lambert R, Nicolet V, Therasse E. Imaging of renovascular hypertension: respective values of renal scintigraphy, renal Doppler US, and MR angiography. Radiographics. Sep-Oct 2000;20(5):1355-68; discussion 1368-72. [Medline].

24. Spitalewitz S, Reiser I. Renovascular hypertension: diagnosis and treatment. In: Oparil S, Weber MA, eds. Hypertension: A Companion to Brenner and Rector's The Kidney. Philadelphia: WB Saunders Co; 2000:662-74.

25. Textor SC. Pitfalls in imaging for renal artery stenosis. Ann Intern Med. Nov 2 2004;141(9):730-1. [Medline].

26. Tullis MJ, Caps MT, Zierler RE, Bergelin RO, Polissar N, Cantwell-Gab K, et al. Blood pressure, antihypertensive medication, and atherosclerotic renal artery stenosis. Am J Kidney Dis. Apr 1999;33(4):675-81. [Medline].

27. Vasbinder GB, Nelemans PJ, Kessels AG, Kroon AA, Maki JH, Leiner T, et al. Accuracy of computed tomographic angiography and magnetic resonance angiography for diagnosing renal artery stenosis. Ann Intern Med. Nov 2 2004;141(9):674-82; discussion 682. [Medline].

28. Working Group on Renovascular Hypertension. Detection, evaluation, and treatment of renovascular hypertension. Final report. Working Group on Renovascular Hypertension. Arch Intern Med. May 1987;147(5):820-9. [Medline].

Keywords

renovascular hypertension, renal artery stenosis, renin-angiotensin-aldosterone, renin-angiotensin-aldosterone system, renin, angiotensin, aldosterone, renin angiotensin, fibromuscular dysplasia, renovascular occlusive disease, atherosclerotic renal artery disease, atherosclerotic renovascular disease, renal artery occlusive disease, RVHT, renal artery occlusion, renal arterial vascular disease, hyperreninemia, arterial occlusive disease, renal ischemia, angiotensin I, angiotensin II, secondary hypertension

Contributor Information and Disclosures

Author

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Coauthor(s)

Sandeep S Soman, MBBS, MD, DNB, Senior Staff Physician, Department of Internal Medicine, Division of Nephrology and Hypertension, Henry Ford Hospital
Sandeep S Soman, MBBS, MD, DNB is a member of the following medical societies: American College of Physicians, American Medical Association, and American Society of Nephrology
Disclosure: Nothing to disclose.

Medical Editor

L Michael Prisant, MD, FACC, Director of Hypertension and Clinical Pharmacology Unit, Professor of Medicine, Department of Medicine, Medical College of Georgia
L Michael Prisant, MD, FACC is a member of the following medical societies: American College of Cardiology, American College of Chest Physicians, American College of Clinical Pharmacology, American College of Forensic Examiners, American College of Physicians, American Heart Association, and American Medical Association
Disclosure: Abbott Grant/research funds Investigator; Boehringer-Ingelheim Grant/research funds Other; Eli Lilly None Investigator; Novartis None Investigator; Abbott, Boehringer-Ingelheim, Forest, Gilead, Merck, Merck/Schering-Plough, Novartis, Oscient, Sciele, SunTech Medical Consulting fee Consulting; Abbott, Boehringer-Ingelheim, Merck, Merck/Schering-Plough, Novartis, Oscient Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine
George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

CME Editor

Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice
Michael E Zevitz, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Medical Association, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

Related eMedicine topics:
Angioplasty, Renal Artery
Fibromuscular Dysplasia
Hyperaldosteronism
Hypertension [Nephrology]
Hypertension [Ophthalmology]
Hypertension, Malignant
Renal Artery Stenosis
Renal Artery Stenosis/Renovascular Hypertension
Renovascular Hypertension, Surgical Treatment

Clinical guidelines:
ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). American College of Cardiology Foundation - Medical Specialty Society
American Heart Association - Professional Association
Society for Cardiovascular Angiography and Interventions - Medical Specialty Society
Society for Vascular Medicine and Biology - Medical Specialty Society
Society for Vascular Surgery - Medical Specialty Society
Society of Interventional Radiology - Medical Specialty Society.  2005.  191 pages.  NGC:004740

ACR Appropriateness Criteria® renovascular hypertension. American College of Radiology - Medical Specialty Society.  1995 (revised 2007).  9 pages.  NGC:006003

The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.].  2004 Aug.  22 pages.  NGC:003761

VHA/DoD clinical practice guideline for the diagnosis and management of hypertension in the primary care setting. Department of Defense - Federal Government Agency [U.S.]
Department of Veterans Affairs - Federal Government Agency [U.S.]
Veterans Health Administration - Federal Government Agency [U.S.].  1999 May (revised 2004).  99 pages.  NGC:004198

Clinical trials:
Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions (CORAL)

Comparison of Best Medical Treatment Versus Best Medical Treatment Plus Renal Artery Stenting (RADAR)

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