eMedicine Specialties > Nephrology > Hypertension and the Kidney
Renovascular Hypertension
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.
Since Goldblatt's seminal experiment in 1934, RVHT has become increasingly 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 renin-angiotensin-aldosterone activation. As demonstrated by Goldblatt, 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.
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.
The sympathetic nervous system does not appear to play a role in perpetuating elevated blood pressure in the 2-kidney 1-clip model of RVHT. Evidence for a role in the 1-kidney 1-clip model of RVHT has been presented but is not clear or definitive.
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
Clinical risk factors include a history of hypertension with azotemia (serum creatinine level >1.5 mg/dL) and modest proteinuria (levels <1.5 g/d) or 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, and hypertension refractory to standard therapy.- 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
Findings suggestive of long-standing hypertension may or may not be evident upon physical examination.- 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.
More on Renovascular Hypertension |
 Overview: Renovascular Hypertension |
| Differential Diagnoses & Workup: Renovascular Hypertension |
| Treatment & Medication: Renovascular Hypertension |
| Follow-up: Renovascular Hypertension |
| Multimedia: Renovascular Hypertension |
| References |
| Further Reading |
| Next Page » |
References
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].
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].
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].
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].
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].
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].
Aurell M, Jensen G. Treatment of renovascular hypertension. Nephron. 1997;75(4):373-83. [Medline].
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].
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].
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].
Canzanello VJ, Textor SC. Noninvasive diagnosis of renovascular disease. Mayo Clin Proc. Dec 1994;69(12):1172-81. [Medline].
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].
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].
Greco BA, Breyer JA. Atherosclerotic ischemic renal disease. Am J Kidney Dis. Feb 1997;29(2):167-87. [Medline].
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].
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].
Kaplan NM. Renal vascular hypertension. In: Clinical Hypertension. 7th ed. Baltimore: Lippincott Williams & Wilkins; 1998:301-21.
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].
Ploth DW. Renovascular hypertension. In: Jacobson H, Striker G, Klahr S, eds. The Principles and Practice of Nephrology. 2nd ed. Philadelphia: BC Decker; 1995:379-86.
Rabbia C, Valpreda S. Duplex scan sonography of renal artery stenosis. Int Angiol. Jun 2003;22(2):101-15. [Medline].
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].
Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med. Feb 8 2001;344(6):431-42. [Medline].
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].
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.
Textor SC. Pitfalls in imaging for renal artery stenosis. Ann Intern Med. Nov 2 2004;141(9):730-1. [Medline].
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].
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].
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].
Further Reading
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)
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
