Renovascular hypertension is one of the most common causes of secondary hypertension. It is mostly due to the narrowing of blood vessels in the kidney. This activity reviews the evaluation and management of renovascular hypertension and highlights the role of the healthcare team in evaluating and treating patients with this condition.
High blood pressure affects 75 million adults in the United States[rx] and accounts for 8.6% of all primary care visits.[rx] Renovascular hypertension is one of the most common causes of secondary hypertension and often leads to resistant hypertension. It is defined as systemic hypertension that manifests secondary to the compromised blood supply to the kidneys, usually due to an occlusive lesion in the main renal artery.
Causes of Renovascular Hypertension
The cause of renovascular hypertension is consistent with any narrowing/blockage of blood supply to the renal organ (renal artery stenosis). As a consequence of this action the renal organs release hormones that indicate to the body to maintain a higher amount of sodium and water, which in turn causes blood pressure to rise. Factors that may contribute are: diabetes, high cholesterol and advanced age,[rx] also of importance is that a unilateral condition is sufficient to cause renovascular hypertension.[rx]
It is important to realize that any condition that compromises blood flow to the kidneys can contribute to renovascular hypertension.[rx] The most common causes of renovascular hypertension include:
The underlying mechanism in renovascular hypertension involves decreased perfusion to the kidney and activation of the Renin-Angiotensin-Aldosterone (RAAS) pathway. This was first explained by Goldblatt et al. in the 1930s. His model studied the effect of decreased blood supply to the kidneys in dogs and found that ischemic kidneys contribute to persistent hypertension. He also proposed the presence of a substance that “may affect a pressor action like that of a hormone.” This hormone he was referring to was ‘renin,’ which is secreted by juxtaglomerular cells of the kidney. Renin secretion by the kidneys is stimulated by three main pathways,
- 1) renal baroreceptors that sense decrease perfusion to the kidney,
- 2) low sodium chloride levels detected by the macula densa and
- 3) beta-adrenergic stimulation. Prolonged ischemia also increases the number of renin expressing cells in the kidney in a process called ‘JG recruitment.’[rx] When renin is secreted into the blood, it acts on angiotensinogen (produced by the liver). Renin cleaves angiotensinogen to angiotensin I, which is then converted to angiotensin II by angiotensin-converting enzyme (ACE) that is primarily found in the vascular endothelium of lungs and kidney. Angiotensin II raises blood pressure by multiple mechanisms, which include:
- Vasoconstriction, mostly in the heart, kidney, and vascular smooth muscle[rx]
Sympathetic nervous stimulation causing a presynaptic release of norepinephrine
Stimulates secretion of aldosterone by the adrenal cortex, which in turn causes sodium and water retention, thereby raising blood pressure.
It also causes the increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis
It has been shown to have a growth effect on renal cells, which has been implicated in the development of glomerulosclerosis and tubulointerstitial fibrosis
Though atherosclerotic renal artery stenosis (ARAS) and FMD are the two most common conditions causing this cascade, any pathology leading to decreased blood flow to the kidneys can essentially trigger this and lead to high blood pressure.
Symptoms Of Renovascular Hypertension
The main symptoms of renovascular hypertension are rapidly increasing blood pressure of 180/120 or higher and signs of organ damage. Usually, the damage happens to the kidneys or the eyes.
Other symptoms depend on how the rise in blood pressure affects your organs. A common symptom is bleeding and swelling in the tiny blood vessels in the retina. The retina is the layer of nerves that line the back of the eye. It senses light and sends signals to the brain through the optic nerve, which can also be affected by renovascular hypertension. When the eye is involved, can renovascular hypertension cause changes in vision.
Other symptoms of malignant hypertension include
- Pheochromocytoma – Sweating, increased frequency or force of heartbeats, headache, anxiety
- Cushing’s syndrome – Weight gain, weakness, abnormal growth of body hair or loss of menstrual periods (in women), purple striations (lines) on the skin of the abdomen
- Thyroid problems – Fatigue (tiredness), weight gain or weight loss, intolerance to heat or cold
- Conn’s syndrome or primary aldosteronism – Weakness due to low levels of potassium in the body
- Obstructive sleep apnea – excessive fatigue or sleepiness during daytime, snoring, pauses in breathing during sleep
- High blood pressure at a young age
- High blood pressure that suddenly gets worse or is hard to control
- Kidneys that are not working well (this can start suddenly)
- Narrowing of other arteries in the body, such as to the legs, the brain, the eyes and elsewhere
- Sudden buildup of fluid in the air sacs of the lungs (pulmonary edema)
- High blood pressure (early age)
- Kidney dysfunction
- Narrowing of arteries elsewhere in the body
- Pulmonary edema
- Change in mental status, such as anxiety, confusion, decreased alertness, decreased ability to concentrate, fatigue, restlessness, sleepiness, or stupor
- Chest pain (feeling of crushing or pressure)
- Nausea or vomiting
- Numbness of the arms, legs, face, or other areas
- Reduced urine output
- Shortness of breath
- Weakness of the arms, legs, face, or other areas
- Blurred vision
- Chest pain (angina)
- Difficulty breathing
- Numbness in the arms, legs, and face
- Severe headache
- Shortness of breath
In rare cases, renovascular hypertension can cause brain swelling, which leads to a dangerous condition called hypertensive encephalopathy. Symptoms include:
- Changes in mental status
- Headache that continues to get worse
- Nausea and vomiting
Diagnosis of Renovascular Hypertension
History and Physical
Salient points in history that suggest the presence of renovascular hypertension include:
Resistant hypertension – Uncontrolled blood pressure necessitating the use of 2 or 3 antihypertensive agents of different classes, one of which is a diuretic
Trial of multiple medications to control blood pressure
History of multiple hospital admissions for hypertensive crisis
Elevation in creatinine of more than 30% after starting an angiotensin-converting enzyme (ACE) inhibitor (ACEI)
Patients with renal artery stenosis secondary to atherosclerosis are usually older and might have the presence of other atherosclerotic diseases such as carotid artery stenosis, peripheral artery stenosis or coronary artery disease
A premenopausal female (15-50 years) with hypertension is most likely to have FMD[rx]
Long term history of smoking
Patients with systemic vasculitis can develop vasculitis of renal arteries and present with renovascular hypertension
Recurrent episodes of flash pulmonary edema and/or unexplained congestive heart failure
Elevation in serum creatinine on starting ACE-I, which occurs due to interference with autoregulation and post glomerular arterial tone
Unexplained hypokalemia and metabolic alkalosis
Unilateral small or atrophic kidney.
Physical examination may reveal an abdominal bruit, indicating the presence of renal artery stenosis.
Patients with renovascular hypertension often undergo an extensive evaluation to find a cause for uncontrolled hypertension.
Urine analysis – to check for proteinuria, hematuria, and casts. The presence of proteinuria indicates the presence of renal parenchymal disorder, whereas the presence of hematuria or RBC casts indicates the presence of glomerulonephritis.
Blood urea nitrogen and serum creatinine – to assess baseline kidney function.
Basal metabolic profile: to assess for electrolyte disturbances and acid-base balance.
Complement levels and autoimmune profile – in suspected cases of autoimmune diseases affecting the renal vasculature.
Plasma free metanephrines or 24-hour urinary fractionated metanephrines and normetanephrine to rule out pheochromocytoma
Plasma renin-aldosterone ratio to rule out hyperaldosteronism
24 hr urinary free cortisol or low dose dexamethasone suppression test to rule out Cushing’s syndrome
- Catheter angiography – There are multiple imaging modalities available to evaluate renovascular hypertension. Since the most common cause of renovascular hypertension is renal artery stenosis, renal arteriography remains the gold standard diagnostic test.[rx] However, catheter angiography is invasive, costly, time-consuming, and can lead to complications such as renal artery dissection or cholesterol embolization. Other imaging tests that can be done to evaluate the renal vessels include duplex ultrasonography, computed tomography with angiography (CTA), and magnetic resonance angiography (MRA). The type of imaging test used often depends on the suspicion for high-grade lesions, and the need for intervention.[rx]
- Duplex ultrasonography – is the initial imaging test of choice to evaluate the renal arteries. It is relatively cheap, non-invasive, and does not involve the administration of contrast or exposure to radiation. A duplex scan has been shown to have an excellent correlation with contrast-enhanced angiography.[rx] Though there are several criteria to assess the presence of renal artery stenosis, the most important sign is peak systolic velocity (PSV). A PSV higher than 180 cm/s suggests the presence of stenosis of greater than 60%.[rx]
- Ultrasonography – can also measure the resistive index (RI), which is calculated as ((PSV-End diastolic velocity)/PSV)). A value of more than 0.7 indicates the presence of pathological resistance to flow, and studies have shown that a value >0.8 predicts poor response to revascularization treatments.[rx] The most significant setbacks for duplex ultrasonography are its reduced sensitivity in obese patients, hindrance by overlying bowel gas and operator dependence.
- CT angiography – involves the administration of intravenous contrast and acquiring detailed images of blood vessels or tissues by moving the beam in a helical manner across the area being studied. In a study by Wittenberg et al, the sensitivity and specificity for hemodynamically significant RAS (>50%) by CTA was found to be 96% and 99%. CTA also has a comparable negative predictive value to MRA in ruling out renal artery stenosis.[rx] It can also diagnose extrinsic compression of renal arteries, FMD, arterial dissection, and help in evaluating surrounding structures. However, CTA can only provide an anatomical assessment of the lesion and is not able to evaluate the degree of obstruction to renal blood flow. Exposure to radiation, allergy to contrast, and acute kidney injury are other downfalls of CTA.
- MRA – uses a powerful magnetic field, pulses of radio waves, and intravenous gadolinium to evaluate the renal blood vessels and surrounding structures. Several studies have shown the sensitivity and specificity of MRA to be around 97% and 92%[rx] in diagnosing renal artery. MRA does not involve radiation, and gadolinium contrast is less likely to cause an allergic reaction as compared to the iodine contrast used in CTA. However, MRA has been shown to overestimate the grade of stenosis and is often affected by motion artifacts or opacification of renal veins, leading to difficulty visualizing the renal arteries. Also, gadolinium has been shown to induce a rare, progressively fatal disease called nephrogenic systemic fibrosis (NSF). NSF can affect the skin, joints, and multiple organs leading to progressive, irreversible fibrosis and eventual death. This occurs due to a transmetalation reaction that displaces gadolinium ion from its chelate, resulting in the deposition of gadolinium in the skin and soft tissues. The 1-year incidence of NSF has been reported to be around 4.6%[rx] and almost all cases occurred in patients with a glomerular filtration rate < 30 mL/min/1.73 m.
- Nuclear medicine ACE-Inhibitor (ACE-I) renography – is another non-invasive, relatively safe imaging method that uses radioactive material, a special camera, and a computer to evaluate for renovascular hypertension. It involves the administration of an ACE-I to determine if the cause of hypertension is due to the narrowing of the renal arteries. The sensitivity and specificity of this test have shown to be variable, with values between 74% – 94% for sensitivity and 59% – 95% for specificity.[rx] It is a time-consuming procedure, and there is a risk of radiation exposure and irritation or pain from the injection of the radiotracer. The sensitivity of ultrasound has shown to be higher than captopril renography[rx] which makes it a better choice for an initial diagnostic test.
- Magnetic resonance angiogram, or MRA – Images from this test show blood flow and organ function without using x-rays. Contrast medium may be injected into a vein in your arm to better see the structure of your arteries. You remain awake, although a muscle relaxer may be used, if necessary. You lie still on a table that slides into a tunnel-shaped device. There is no radiation exposure with this study. Claustrophobia can be an issue with MRAs as the tube is quite narrow.
- Catheter angiogram – A special kind of x-ray in which a catheter, or a thin, flexible tube, is threaded through your large arteries into your renal artery. This often is from a small slit in the groin. The patient is usually awake, although a muscle relaxer may be given to lessen anxiety during the procedure. A contrast medium, or a colored dye, is injected through the catheter, so the renal artery shows up more clearly on the x-ray. The benefits of this study are that it is more accurate than the other tests and if a significant narrowing is seen, it can be dilated with a balloon (angioplasty) or stented (a tube-like cage that keeps the vessels open) at the same time. A catheter angiogram is an invasive procedure so this is usually reserved for patients who have a positive result of one of the other tests and plans are made to dilate the blood vessel.
Catheter arteriography – is the gold standard test to evaluate for renovascular hypertension and provides the best temporal and spatial resolution. Catheter angiography has the added advantage of measuring translesional pressure gradients to assess the hemodynamic significance of anatomically severe lesions.[rx] It is most useful in:
Patients with a disparity between imaging modalities
Patients with a high index of suspicion and negative imaging findings
Patients anticipated having an intervention
It can also evaluate anatomical abnormalities of the kidney, renal arteries, aorta, and can be followed by endovascular intervention for the treatment of significant lesions. Also, the surrounding tissues and bones can be removed or subtracted from the final image revealing only the arterial framework. This method is known as digital subtraction angiography (DSA). However, the radiation doses are higher than CTA, and because it is an invasive procedure, there are risks of complications such as arterial dissection, tear, rupture, or thromboembolic phenomenon.[rx]
Treatment of Renovascular Hypertension
The management of renovascular hypertension aims to treat the underlying cause. Several options are available, which include pharmacological and invasive therapy.
Pharmacological therapy entails the use of antihypertensive medications to control blood pressure. The American College of Cardiology and the American Heart Association (ACC/AHA) advocates pharmacological therapy as the first-line treatment for renal artery stenosis.[rx] Since RAAS is the most prominent pathway contributing to hypertension in these disorders,
- ACEI and angiotensin receptor blockers (ARBs) form the cornerstone of managing renovascular hypertension (Class 1a indication). Often more than one medication will be needed to control the blood pressure.
- Calcium channel blockers, thiazides, beta-blockers, and hydralazine have been shown to be effective to control blood pressure in patients with RAS.[rx] Direct renin inhibitors such as aliskiren have been studied as monotherapy or in combination with ACEIs/ARBs to treat hypertension. Though it has been shown to be effective for the treatment of hypertension[rx][rx][rx][rx][rx] there is not enough data to prove its efficacy in treating renovascular hypertension.
- ACEIs and ARBs inhibit the action of angiotensin II, thereby causing vasodilation and promote sodium and water excretion. However, these medications are contraindicated in patients with a single functioning kidney or bilateral lesions as they can cause efferent arteriolar vasodilatation leading to interruption in autoregulation and thereby decreasing glomerular filtration. While these medications are effective in controlling blood pressure, they can also lead to worsening renal function.
- Percutaneous angioplasty is the treatment of choice for renovascular hypertension due to FMD and for patients with atherosclerotic renal artery stenosis that is not controlled with medications.[rx] The ACC/AHA guidelines recommend revascularization for renal artery disease in the following scenarios:[rx]
Patients with hemodynamically significant RAS and recurrent, unexplained congestive heart failure or sudden, unexplained pulmonary edema (class Ia)
Hemodynamically significant RAS and accelerated hypertension, resistant hypertension, malignant hypertension or hypertension with an unexplained unilateral small kidney, and hypertension with intolerance to medication (Class IIa)
Patients with bilateral RAS and progressive chronic kidney disease or a RAS to a solitary functioning kidney (Class IIa)
Patients with hemodynamically significant RAS and unstable angina (class IIa)
Asymptomatic bilateral or solitary viable kidney with hemodynamically significant RAS (Class IIb)
Patients with RAS and chronic renal insufficiency with unilateral RAS (class IIb)
In addition to angioplasty, renal stent placement is indicated for patients with ostial atherosclerotic lesions (Class I).
Patients with FMD and renovascular hypertension are also treated with percutaneous intervention with or without a stent.[rx] Multiple studies have shown a decrease in baseline blood pressure after intervention for FMD.[rx][rx] However, there remains an ongoing debate about the benefit of revascularization when compared to medical management in patients with atherosclerotic renal artery stenosis (ARAS). Several studies have failed to show a significant decrease in blood pressure or the number of antihypertensive agents between angioplasty and medical treatment groups.
A meta-analysis of 7 trials by Zhu et al. revealed that medical management is as effective as percutaneous revascularization in the treatment of RAS.[rx] Three recent trials ASTRAL, CORAL, and STAR found no difference between stenting and medical therapy in patients with atherosclerotic renal artery stenosis.[rx] [rx][rx] Thus it can be established that revascularization does not reverse renal damage or decrease blood pressure in patients with atherosclerotic renal artery stenosis.
In the case of recurrent renal artery stenosis or blood pressure not controlled with medication and or/angioplasty, renal bypass surgery may be an option. In this procedure, the surgeon uses a vein or synthetic tube to connect the kidney to the aorta, to create an alternate route for blood to flow around the blocked artery into the kidney. This is a complex procedure and rarely used. The ACC/AHA guidelines recommend surgery for RAS in[rx]
Patients with RAS secondary to FMD, especially those with complex disease and/or those having microaneurysms
Patients with atherosclerotic RAS involving multiple vessels or involvement of early primary branch of the main renal artery
Patients with atherosclerotic RAS who require pararenal aortic reconstructions (such as with aortic aneurysms or severe aortoiliac obstruction).
Several studies have also evaluated the role of unilateral nephrectomy in patients with renovascular hypertension and have shown improvement in blood pressure control, renal function, and decrease in the use of anti-hypertensives.[rx][rx] However, this is an invasive procedure with inherent risks and long term consequences of such a procedure are unclear.
- In terms of treatment for renovascular hypertension surgical revascularization versus medical therapy for atherosclerosis, it is not clear if one option is better than the other according to a 2014 Cochrane review; balloon angioplasty did show a small improvement in blood pressure .[rx]
- Surgery can include percutaneous surgical revascularization, and also nephrectomy or autotransplantation, and the individual may be given beta-adrenergic blockers.[rx] Early therapeutic intervention is important if ischemic nephropathy is to be prevented. Inpatient care is necessary for the management of hypertensive urgencies, quick intervention is required to prevent further damage to the kidneys.[rx]
Blood Pressure Goals
SHEP and HYVET trials have shown significant benefits of antihypertensive treatment in patients with the goal of SBP <150 mmHg[rx].
The VALsartan in Elderly Isolated Systolic Hypertension (VALISH) trial showed no significant difference in the primary outcome of sudden death, fatal or nonfatal myocardial infarction and stroke, heart failure death, or other cardiovascular death among patients with strict (< 140 mmHg) and moderate (140 to 150 mmHg) SBP control[rx].
However, the VALISH trial was underpowered due to the low number of events.
Hence, the optimal SBP in patients with hypertensive disorder remained a controversial topic.
The most recent Systolic Blood Pressure Intervention Trial (SPRINT) has shown that intensive SBP target of < 120 mmHg improved the cardiovascular outcomes and the overall survival compared to the standard SBP target of 135 to 139 mmHg[rx].
However, aggressive SBP lowering may be harmful in the elderly and incite more adverse effects such as hypotension, end-organ hypoperfusion (causing acute kidney injury, and intracranial hypoperfusion which may link to cognitive decline), and polypharmacy.
It is suggested that a goal blood pressure of < 130/80 mmHg is appropriate as long as the patient tolerates it.
Otherwise, < 140/90 mmHg is considered reasonable in patients who are in the elderly population and patients with labile blood pressure or polypharmacy.
Management strategies should always be patient-centered, with the aim of optimizing blood pressure control and avoiding polypharmacy, especially in the elderly.
Various studies have shown a J-curve association between blood pressure with risk of myocardial infarction and death.
As myocardial perfusion occurs mainly during diastole, an excessive drop in DBP may increase the risk of cardiovascular disease and death.
You may also need to make some lifestyle changes as part of your ISH treatment plan. These can include:
- Losing weight. This can help lower your blood pressure. In fact, for every two pounds you lose, you could lower your blood pressure by about 1 mm Hg.
- Eating a heart-healthy diet. You should also aim to reduce the amount of sodium in your diet. Consider the DASH diet, which emphasizes eating:
- whole grains
- low-fat dairy products
- Exercising. Not only can exercise help you lower your blood pressure, but it can help you control your weight and stress levels. Aim to perform some sort of aerobic exercise for at least 30 minutes most days of the week.
- Decreasing alcohol consumption. Healthy alcohol intake is one drink per day for women and two per day for men.
- Quitting smoking. Smoking can raise your blood pressure and also contribute to a variety of other health problems.
- Managing stress. Stress can raise your blood pressure, so finding ways to relieve it are important. Examples of techniques to help lower stress are meditation and deep breathing exercises.
- Eating a heart-healthy diet: Choose fruits, vegetables, grains and low-fat dairy foods.
- Exercising regularly, at least 30 minutes a day of moderate activity, such as walking (check with your healthcare provider before starting an exercise program).
- Keeping your weight under control: Check with your healthcare provider for a weight-loss program, if needed.
Cutting back on alcoholic drinks.
- Limiting caffeine intake.
- Limiting sodium (salt) in your diet: Read nutrition labels on packaged foods to learn how much sodium is in one serving.
- Reducing and avoiding stress when possible: Many people find that regular meditation or yoga helps.