Renovascular Hypertension

Objectives Causes Clinical Presentation Diagnosis Treatment Background

Background Renovascular hypertension (RVHT) denotes the causal relationship between anatomically evident arterial occlusive disease and elevated blood pressure. RVHT is the clinical consequence of renin-angiotensin-aldosterone activation.

Proposed pathogenesis of renovascular hypertension

In unilateral renal artery stenosis (RAS), renin production is increased by the ischemic kidney but suppressed in the unaffected non-stenotic kidney, which lacks the same ischemic stimulus. Consequently, when 2 kidneys are present with a unilateral stenosis, hyperreninemia persists and blood pressure remains elevated because of an angiotensin II–induced vasoconstrictive effect.

In late stage, hypertension often is unremitting, persisting well after the removal of the stenosis. 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.

Classification and Causes Atherosclerotic disease is the most common form of renal artery stenosis and the most common cause of renovascular hypertension in the Western world. It accounts for 70%- 80% of renal artery lesions and it affect mainly the proximal third of the main renal artery and is seen mostly in older men.

Classification and Causes Fibroplastic disease is most common cause of renovascular hypertension in persons younger than 40 years, involving mainly the distal two thirds and branches of the renal arteries appears most commonly in women.

As the population grows older, 90% of cases are caused by atherosclerotic disease and only 10% by fibroplastic disease. 3. Other (Aortic/renal dissection, Takayasu’s arteritis, Thrombotic/cholesterol emboli, Post transplantation stenosis, Post radiation, Neurofibromatosis, Arterial trauma)

Renovascular causes Renal artery stenosis Fibromuscular dysplasia

Frequency 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.

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

Clinical Clues for Renovascular Hypertension History Onset of hypertension before 30 or after 50 yr of age Abrupt onset of hypertension Severe or resistant hypertension Symptoms of atherosclerotic disease elsewhere Negative family history of hypertension Smoker Worsening renal function after renin-angiotensin inhibition Recurrent flash pulmonary edema Moderate-to-severe hypertension in a patient with an unexplained atrophic kidney, asymmetric kidneys of greater than 1.5 cm difference or diffuse atherosclerosis

Clinical Clues for Renovascular Hypertension 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. Systolic-diastolic bruits in combination with hypertension are suggestive of RVHT.

Clinical Clues for Renovascular Hypertension Laboratory Findings Secondary aldosteronism Higher plasma renin level Low serum potassium level Low serum sodium level Proteinuria, usually moderate Elevated serum creatinine level >1.5-cm difference in kidney size on sonography

Differential diagnosis Acute renal failure Chronic glomerulonephritis Malignant HTN causing renal failure Hypersensitivity nephropathy Nephrosclerosis Essential and other causes of hypertension with renal insufficiency

Laboratory Studies: Serum creatinine and creatinine clearance. 24-hour urine protein: Vascular renal disease is associated with minimal-to-moderate degrees of proteinuria, which are rarely in the nephrotic range. Urinalysis shows absence of red blood cells or red blood cell casts (a hallmark of glomerulonephritis).

Laboratory Studies: Serologic tests for SLE or vasculitis. Measurement of plasma renin activity: The baseline plasma renin activity is elevated in 50-80% of patients with RVHT. Captopril Provocation Test: Measuring the increase in the baseline plasma renin activity 1 hour after the administration of 25-50 mg of captopril. Patients with RAS have an exaggerated increase in baseline plasma renin activity.

Laboratory Studies: (Cont.) Renal vein renin ratio ≥ 1.5 between stenotic/contralateral kidney predicting 90% cure or improvement of HTN with PTRA or surgical intervention (although PTRA or surgery will also benefit one-third to half the patients without lateralizing renal vein renin ratios).

Imaging Studies Ultrasound/Duplex ultrasound: May show significant asymmetry of kidney size (i.e. size discrepancy of >1.5 cm). Additionally, US may be useful to determine the presence of a solitary kidney. 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

Imaging Studies Captopril renography: Administration of captopril orally (25-50 mg) 1 hour before the isotope is injected. ACE inhibitor 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. In patients with normal, or near-normal, renal function, a normal captopril renogram essentially excludes functionally significant renal artery stenosis.

Imaging Studies (cont.) Renal arteriography: 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.

Imaging Studies (cont.) Magnetic resonance angiography: MRA is a very good noninvasive technique capable of demonstrating the renal vascular anatomy and direct visualization of renal artery lesions without iodinated contrast material. The limitations of MRA are its expense and its contraindication in patients with pacemakers, metallic devices, or other implants.

RAS screening/diagnostics Limitation Specificity Sensitivity Operator dependent, 10-20% 60-90% 90-95% Duplex U/S Accuracy reduced in pt with renal insufficiency, lacks anatomical info; good predictor of BP response 87-93% 83-91% Captopril Renography Accuracy is lower in renal impairment possibly due to reduced renal blood flow. 94%, 98% Spiral CT False positive , cost 71-96% 96-100% MRA Insensitive, severe stenosis may be silent 90-99% 39-65% Bruit Invasive, nephrotoxicity, little value in predicting BP response Gold std Angiography

Treatment Cessation of smoking. Antidyslipidemic therapy for those patients with hyperlipidemia. Optimal blood pressure control plays an essential role in the therapeutic management. Percutaneous transluminal renal angioplasty(PTRA) Surgical revascularization. Trials comparing renal artery revascularization with medical management do not unequivocally favor surgical over medical intervention.

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. 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. In patients with diffuse atherosclerosis, the complication rate with either surgery or angioplasty is relatively high. Medical therapy may be preferred.

ARBs: appear to be as effective as ACE inhibitors in experimental models. A selective aldosterone inhibitor, eplerenone (INSPRA) is now available for the treatment of hypertension. Beta-blockers: Actions include a negative chronotropic effect, a negative inotropic effect, a reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Diuretics also are used, often in conjunction with ACE inhibitors. Calcium channel blockers (CCBs) may provide equally good control of hypertension.

The decision to recommend intervention (i. e The decision to recommend intervention (i.e., operation or percutaneous transluminal renal angioplasty [PTRA], or renal artery stent) Duration of hypertension <3-5 yr. Positive findings on captopril renogram. Renal vein renin ratio >1.5. Hypokalemia. Systolic-diastolic bruit in abdomen. Abnormal rapid-sequence intravenous pyelogram. Appearance of lesion on angiogram (>75% stenosis).

Percutaneous transluminal renal angioplasty (PTRA) Cure reported in 50-85% of patients in the fibromuscular dysplasia , and in 8-20% of persons in atherosclerotic stenosis 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. In patients with diffuse atherosclerosis, the complication rate with both surgery and angioplasty is relatively high.

Complications of RVHT End-organ damage from chronically uncontrolled hypertension. Progressive renal failure Chronic renal ischemia

Prognosis Patients with fibromuscular disease have more favorable outcomes than patients with atherosclerotic lesions, presumably owing to their younger age, shorter duration of hypertension, and less systemic disease. In atherosclerotic patients, vascular repair should be considered if blood pressure cannot be adequately controlled with medical therapy or if renal function deteriorates.

Bilateral renal artery stenosis