High blood pressure affects 75 million adults in the United States and accounts for 8.6% of all primary care visits. 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.
It is important to realize that any condition that compromises blood flow to the kidneys can contribute to renovascular hypertension. The most common causes of renovascular hypertension include:
Providing care for uncontrolled hypertension costs $48.6 billion each year. Although the majority of these cases are due to essential hypertension, around 10% of these patients have secondary hypertension. Studies have shown renovascular hypertension to be the underlying etiology in about 75% of the cases of secondary hypertension.
Renovascular hypertension affects people of all ages. Renal artery stenosis secondary to atherosclerosis is the most common cause and is mostly seen in older adults (>65 years). It has a higher prevalence in patients with known atherosclerotic disease (such as those with coronary artery disease, peripheral artery disease or carotid artery stenosis) and autopsy studies have revealed that "greater than 25% of all patients who die of cardiovascular disease have some degree of RAS.” Fibromuscular Dysplasia (FMD) is usually seen in young women and accounts for around 10% of renovascular hypertension and 5.8% of secondary hypertension. FMD can affect any arterial bed but most commonly affects the distal two-thirds of the renal artery.
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.’ 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:
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.
Salient points in history that suggest the presence of renovascular hypertension include:
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.
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. 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.
Duplex ultrasonography is the initial imaging test of choice to evaluate the renal arteries. It is relatively cheap, non-invasive, and does not involve administration of contrast or exposure to radiation. A duplex scan has been shown to have an excellent correlation with contrast-enhanced angiography. 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%.
Duplex 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. 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 comparable negative predictive value to MRA in ruling out renal artery stenosis. 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% 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 which displaces gadolinium ion from its chelate, resulting in deposition of gadolinium in the skin and soft tissues. The 1-year incidence of NSF has been reported to be around 4.6% and almost all cases occurred in patients with a glomerular filtration rate < 30 mL/min/1.73 m.
In comparative studies, the positive predictive value of MRA was found to be higher than CTA due to increased false-positive rates with CTA. Negative predictive values are high for both CTA and MRA (>98% for both). Both modalities can exclude significant renal artery lesions with a high degree of certainty. Both MRA and CTA have also shown to be effective for the diagnosis of FMD, with the sensitivity of CTA being the best (84.2%) when compared to angiography.
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. 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 which makes it a better choice for an initial diagnostic test.
Catheter angiography 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. It is most useful in:
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.
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. 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. 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 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. The ACC/AHA guidelines recommend revascularization for renal artery disease in the following scenarios:
Patients with FMD and renovascular hypertension are also treated with percutaneous intervention with or without a stent. Multiple studies have shown a decrease in baseline blood pressure after intervention for FMD. 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. Three recent trials ASTRAL, CORAL, and STAR found no difference between stenting and medical therapy in patients with atherosclerotic renal artery stenosis.  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:
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. However, this is an invasive procedure with inherent risks and long term consequences of such a procedure are unclear.
The differential diagnosis for renovascular hypertension includes potential causes of secondary hypertension, such as:
Atherosclerotic renal artery stenosis is a progressive disorder that can lead to worsening stenosis and, ultimately, renal failure. In previous studies, the 3-year cumulative incidence of disease progression was found to be 18%, 28%, and 49% for renal arteries classified as normal, <60% stenosis and >60% stenosis. High blood pressure (systolic >160 mm hg), diabetes mellitus, and high-grade stenosis (>60% obstruction) have been shown to be associated with an increased rate of progression. Untreated renovascular hypertension can also lead to end-stage renal failure with a median survival time of 25 months and a 4-year mortality rate of 35%. Primary management of renovascular hypertension should aim to correct the underlying cause. Renovascular hypertension due to atherosclerotic renal artery stenosis should be primarily managed medically as multiple studies have failed to show renal or cardiovascular benefits with invasive management.
Complications of Renovascular hypertension are mostly due to uncontrolled blood pressure and include:
Renovascular hypertension happens when the blood flow to the kidneys is compromised, leading to high blood pressure through a hormonal response by the affected kidney. This is a serious condition and can lead to complications such as heart attack, stroke, and even death. Patients who continue to have high blood pressure in spite of being on multiple blood pressure medications should initiate a discussion regarding the possibility of renovascular hypertension. The clinical provider should also have a high index of suspicion in patients with resistant hypertension and pursue appropriate diagnostic modalities.
Uncontrolled hypertension consumes significant healthcare resources worldwide. Knowledge about the clinical presentation, possible etiologies, evaluation, and management of renovascular hypertension is important for all healthcare professionals to improve clinical outcomes. The management of this condition necessitates an interprofessional approach to ensure timely diagnosis and management of this condition. The primary provider needs to have a high index of suspicion to pursue this diagnosis early in the course of the disease. The clinical nurse needs to ensure the patient is compliant with medical therapy for hypertension before he or she is labeled as one having resistant hypertension. Patient education by a specialized nurse is equally important in incorporating lifestyle changes to treat hypertension. Pharmacists play a crucial role in ensuring proper dosing and compliance with therapy. Educating the patient on potential complications of medical therapy is equally important and requires a specialized pharmacist to pursue this task. A team of specialized providers, including a primary care provider, cardiologist, nephrologist, radiologist, and a vascular surgeon, may eventually be needed to properly diagnose and treat a patient with renovascular hypertension. Since medical management is as effective as surgical interventions in most cases of renovascular hypertension, it is important to focus on pharmacological therapies as first-line to treat this disorder. When all healthcare providers function as a cohesive interprofessional team, outcomes will show improvement. [Level 5]
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