Renal Artery Diseases
Vascular providers are frequently asked to comment on or manage different forms of renal artery disease with a wide range of etiology, pathophysiology, and natural history. From renal artery aneurysms to fibromuscular dysplasia (FMD) to atherosclerotic occlusive disease, all forms of renal artery disease have two common endpoints of clinical concern; one related to blood pressure elevation and the other to deterioration of renal excretory function. Renal artery disease either from atherosclerosis or fibromuscular dysplasia is the most common cause of secondary hypertension and is present in about 5% of the elderly population. A recent study of patients referred to a university vascular laboratory identified significant occlusive disease in nearly a quarter of patients, a finding that was more common in those receiving two or more blood pressure medications. In the context of all patients with hypertension, renovascular occlusive disease is responsible for only about 5% of cases. While this percentage seems low, the growing number of Americans with hypertension (31% of the U.S. population or 65 million individuals in 2000) makes the prevalence of this vascular disease process significant, especially in an aging population.
Tremendous gains have been made in the understanding of the natural history of renal artery disease although issues surrounding the indications for and timing of renal artery intervention (open or endovascular) remain somewhat unsettled. The topic of renal artery intervention remains a major clinical challenge in large part because of advancing technologies on all sides of the matter (diagnostic, pharmacologic, and endovascular). There is little question that renal artery occlusive disease accelerates the development of hypertension through activation of pressor systems and, if severe enough, ultimately results in ischemic damage to renal excretory function. Untreated hypertension results in end-organ damage affecting the heart, brain, peripheral vascular, and ophthalmologic systems, as well as the kidneys themselves.
Except for a subset of pediatric patients with renovascular hypertension, most patients referred to the vascular provider for evaluation of renal disease are elderly with chronic hypertension and other comorbidities such as diabetes mellitus. The benefit of an extensive anatomic workup of the renal arteries in these patients is not always clear, as antihypertensive drug therapy has been shown to be quite effective. Medications that block the renin-angiotensin system, either conventional angiotensin-converting enzyme inhibitors (ACE inhibitors) or the newer angiotensin-II receptor blockers (ARBs) have become first-line therapy. And when combined with beta-receptor blockers or calcium channel blockers these medications suffice in treating hypertension even in the presence of renal artery disease in most patients.
The challenge comes when patients require more than 2 or 3 medications to control hypertension or have deterioration of
renal function or kidney size. Imaging of the renal arteries and selection of appropriate patients for renal revascularization in this group is really at the center of the clinical challenge. Unfortunately, treatment decisions in these patients are not always guided by high levels of clinical evidence, although this is an area of intense interest and clinical study. One trial that is underway is the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study, which randomly assigns subjects with proven, high-grade, renal artery lesions to optimal medical management with and without renal stenting. Understanding the best role for renal artery intervention depends greatly on how such well-designed clinical trials are conducted.
renal function or kidney size. Imaging of the renal arteries and selection of appropriate patients for renal revascularization in this group is really at the center of the clinical challenge. Unfortunately, treatment decisions in these patients are not always guided by high levels of clinical evidence, although this is an area of intense interest and clinical study. One trial that is underway is the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study, which randomly assigns subjects with proven, high-grade, renal artery lesions to optimal medical management with and without renal stenting. Understanding the best role for renal artery intervention depends greatly on how such well-designed clinical trials are conducted.
This chapter aims to summarize basic principles related to renovascular hypertension and renal artery disease and reviews indications for and basic principles of the diagnostic evaluation. Indications for renal artery interventions, open and/or endovascular, are also discussed, including techniques and periprocedural care.
I. Renin-angiotensin system.
To logically manage renovascular hypertension, one must review the relationship of the kidney to blood pressure control. By adjusting sodium and water retention and through the release of vasoactive factors, the kidney functions as an endocrine organ helping to maintain blood pressure through several mechanisms. A hemodynamically significant obstruction or stenosis of the renal artery or an overall decrease in blood volume decreases blood flow to the kidney. This decrement in blood flow is “viewed” by the kidney as hypovolemia or hypotension and initiates a response from that kidney that involves release of local and circulating factors. Specifically, baroreceptors in the juxtaglomerular apparatus of the kidney detect decreases in renal blood flow and respond by releasing the enzyme renin. Renin cleaves the serum globulin angiotensin I, forming the vasoactive peptide angiotensin II, which increases renal blood flow by several mechanisms. Angiotensin II stimulates adrenal release of aldosterone, causes systemic vasoconstriction, and exerts an antidiuretic, antinatriuretic action on the kidney (i.e., fluid or volume retention). Angiotensin II also causes vasoconstriction of the efferent arterioles of the juxtaglomerular apparatus, decreasing flow from this system and producing a subsequent rise in pressure. The result is sodium and water retention, expansion of extracellular fluid volume, and an increase in systemic blood pressure. One very effective class of medications used to treat hypertension includes several that inhibit conversion of angiotensin I to angiotensin II (ACE inhibitors) or directly block the angiotensin II receptor (ARBs).
II. Diagnostic evaluation of the renal arteries should be performed only in appropriate clinical circumstances.
As was noted previously, 5-10% of patients with hypertension have some form of renal artery disease resulting in a functional renal artery stenosis. This association occurs more often in hypertensive children and young adults, who more commonly have aortic coarctation, congenital renal artery stenosis, or fibromuscular dysplasia. In this population of young individuals with significant hypertension, diagnostic evaluation of the renal arteries is
warranted early in their evaluation to look for congenital abnormalities or FMD.
warranted early in their evaluation to look for congenital abnormalities or FMD.
In contrast, elderly adults are most commonly affected by essential hypertension, and routine diagnostic evaluation of the renal arteries is not necessary early in the course of their workup. In these cases, even though at risk for atherosclerosis and renal artery disease, initiation of one or two medications along with risk factor modification is usually effective in reducing blood pressure. A thorough history and physical exam should be performed and routine lab tests, including serum creatinine and creatinine clearance, should be performed. If there is no indication from the history, physical, or lab testing that the renal arteries are involved, basic medical management (e.g., one or two medications) may be initiated without diagnostic evaluation of the renals. If this strategy, which includes risk modification and exercise, is not effective at achieving a desirable blood pressure within 3 months, diagnostic evaluation of the renal arteries should be performed.
Diagnostic tests of choice to identify and measure renal artery disease vary among institutions. However, initial evaluation should begin with noninvasive tests such as duplex ultrasound, CTA, and MRA. The vascular provider should be mindful that only duplex spares the patient from the nephrotoxic effects of contrast needed with CTA and MRA, and is therefore the preferred diagnostic test. Invasive renal artery arteriography should be performed sparingly and reserved for cases in which an intervention is planned. Alternatively, angiography is indicated for instances in which noninvasive studies are inconclusive or in disagreement, and the information regarding renal artery anatomy is imperative in clinical decision-making process.
A. Screening tests. Duplex ultrasound is the primary noninvasive test of choice in screening for renal artery disease.
Renal duplex requires the patient to fast in order to reduce the amount of bowel gas interference with the study. Evaluation of the renal arteries with duplex also requires an experienced vascular technologist and about 45 to 60 minutes of time (Chapter 6). Another noninvasive option for evaluation of the renal arteries is gadolinium-enhanced magnetic resonance angiography. MRA has the advantage of imaging the entire aorta and branch vessels and can often provide quite remarkable images. MRA is especially useful in cases of renal artery aneurysms and FMD. However, quality of MRA is often institution-specific and some vascular specialists see MRA as overestimating the degree of renal artery occlusive disease. Furthermore, MRA is relatively expensive, and is not always tolerated by patients who may be claustrophobic. In our practice, we use MRA as a backup for renal duplex imaging that provides inconclusive or equivocal results. Similar to MRA, CTA of the renal arteries can provide exceptional images of the aorta, main renal arteries, and renal hilum. Unfortunately, the contrast necessary to achieve such imaging carries a significant nephrotoxic effect and often precludes use of this noninvasive imaging modality. We rarely use dedicated CTA to image the renal arteries in the setting of suspected renovascular hypertension and save this modality for patients with
renal artery aneurysms or congenital renal abnormalities in younger patients who have normal renal function.
renal artery aneurysms or congenital renal abnormalities in younger patients who have normal renal function.
Two functional tests for renovascular hypertension that are currently used sparingly, are the captopril test and captopril renal scanning. The captopril test involves oral administration of captopril, an ACE inhibitor, after baseline measurement of plasma renin activity and blood pressure. Renovascular hypertension should be suspected when the post-captopril plasma renin level is excessively high. Some older studies indicate that the sensitivity of this test approaches 100%, with a specificity of 90%. However, the test is less accurate in the presence of renal insufficiency. Criteria for a positive captopril renal scan include a reduction in glomerular filtration rate and a delay in the time to peak clearing of the radionuclide.
B. Arteriography carries the nephrotoxic risk of contrast material and should be performed only when an intervention is planned or when noninvasive studies are inconclusive or in disagreement and information regarding renal artery anatomy is imperative in clinical decision making.
The more selective use of renal arteriography is an advance in the management of this vascular condition and is a testament to improvements in noninvasive vascular imaging (e.g. duplex and MRA) and an improved understanding of which patients benefit from renal intervention.
When performed, renal arteriography should include (a) an abdominal aortogram, (b) selective renal artery injections in different planes, and (c) a celiac artery injection with a lateral view if the splenic or hepatic arteries are being considered for open splenorenal or hepatorenal bypass. The amount of contrast should be minimized in all patients with suspected renovascular disease, and imaging adjuncts such as CO2 aortography and intravascular ultrasound (IVUS) often aid in this objective.
C. Renal vein renin determination is mentioned mostly as a historical note as few vascular specialists continue to use this test in day-to-day practice.
Renal vein renin determination has fallen out of favor because of its invasive nature, technical requirements, and often nonspecific findings. The concept behind renal vein renin measurements is as follows: The presence of a renal artery stenosis on an imaging test does not establish its functional importance (e.g., whether it is causing renin release and hypertension). To explore this question, a comparison of renin from venous samples taken from each renal vein and the inferior vena cava above and below the renal veins provides insight into the significance of a renal artery stenosis. Since a kidney that is truly ischemic will produce increased amounts of renin, a renal vein ratio of at least 1.5:1.0 should be present if the renal artery stenosis is significant.
Different aspects of renin determinations complicate the ability to achieve meaningful results. Antihypertensive medications such as beta-blockers, which suppress renin secretion as well as variations in sodium intake, affect renal vein renin assay and often result in nonlateralization of renal vein renins (i.e., an indeterminate finding). One way to stimulate a
difference in renal vein renins is captopril administration after baseline renins are collected. Renin levels are again collected 30 minutes after captopril and a post-captopril renal venous ratio of 3 increases the sensitivity of the test. Despite the past value of renal vein renins, their use in everyday clinical practice has diminished in recent years.
difference in renal vein renins is captopril administration after baseline renins are collected. Renin levels are again collected 30 minutes after captopril and a post-captopril renal venous ratio of 3 increases the sensitivity of the test. Despite the past value of renal vein renins, their use in everyday clinical practice has diminished in recent years.
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