Large-vessel renal artery occlusive disease can result from extrinsic compression of the vessel, fibromuscular dysplasia, or, most commonly, atherosclerotic disease. Any disorder that reduces perfusion pressure to the kidney can activate mechanisms that tend to restore renal pressures at the expense of developing systemic hypertension. Because restoration of perfusion pressures can reverse these pathways, renal artery stenosis is considered a specifically treatable “secondary” cause of hypertension.
Renal artery stenosis is common and often has only minor hemodynamic effects. Fibromuscular dysplasia (FMD) is reported in 3–5% of normal subjects presenting as potential kidney donors without hypertension. It may present clinically with hypertension in younger individuals (between age 15 and 50), most often women. FMD does not often threaten kidney function, but sometimes produces total occlusion and can be associated with renal artery aneurysms. Atherosclerotic renal artery stenosis (ARAS) is common in the general population (6.8% of a community-based sample above age 65), and the prevalence increases with age and for patients with other vascular conditions such as coronary artery disease (18–23%) and/or peripheral aortic or lower extremity disease (>30%). If untreated, ARAS progresses in nearly 50% of cases over a 5-year period, sometimes to total occlusion. Intensive treatment of arterial blood pressure and statin therapy appear to slow these rates and improve clinical outcomes.
Critical levels of stenosis lead to a reduction in perfusion pressure that activates the renin-angiotensin system, reduces sodium excretion, and activates sympathetic adrenergic pathways. These events lead to systemic hypertension characterized by angiotensin dependence in the early stages, widely varying pressures, loss of circadian blood pressure (BP) rhythms, and accelerated target organ injury, including left ventricular hypertrophy and renal fibrosis. Renovascular hypertension can be treated with agents that block the renin-angiotensin system and other drugs that modify these pressor pathways. It can also be treated with restoration of renal blood flow by either endovascular or surgical revascularization. Most patients require continued antihypertensive drug therapy because revascularization alone rarely lowers BP to normal.
ARAS and systemic hypertension tend to affect both the post-stenotic and contralateral kidneys, reducing overall glomerular filtration rate (GFR) in ARAS. When kidney function is threatened by large-vessel disease primarily, it has been labeled ischemic nephropathy. Moderately reduced blood flow that develops gradually is associated with reduced GFR and limited oxygen consumption with preserved tissue oxygenation. Hence, kidney function can remain stable during medical therapy, sometimes for years. With more advanced disease, reductions in cortical perfusion and frank tissue hypoxia develop. Unlike FMD, ARAS develops in patients with other risk factors for atherosclerosis and is commonly superimposed upon preexisting small-vessel disease in the kidney resulting from hypertension, aging, and diabetes. Nearly 85% of patients considered for renal revascularization have stage 3–5 chronic kidney disease (CKD) with GFR below 60 mL/min per 1.73 m2. The presence of ARAS is a strong predictor of morbidity- and mortality-related cardiovascular events, independent of whether renal revascularization is undertaken.
Diagnostic approaches to renal artery stenosis depend partly on the specific issues to be addressed. Noninvasive characterization of the renal vasculature may be achieved by several techniques, summarized in Table 44-1. Although activation of the renin-angiotensin system is a key step in developing renovascular hypertension, it is transient. Levels of renin activity are therefore subject to timing, the effects of drugs, and sodium intake, and do not reliably predict the response to vascular therapy. Renal artery velocities by Doppler ultrasound above 200 cm/s generally predict hemodynamically important lesions (above 60% vessel lumen occlusion), although treatment trials require velocity above 300 cm/s to avoid false positives. The renal resistive index has predictive value regarding the viability of the kidney. It remains operator- and institution-dependent, however. Captopril-enhanced renography has a strong negative predictive value when entirely normal. Magnetic resonance angiography (MRA) is now less often used, as gadolinium contrast has been associated with nephrogenic systemic fibrosis. Contrast-enhanced computed tomography (CT) with vascular reconstruction provides excellent vascular images and functional assessment, but carries a small risk of contrast toxicity.
TABLE 44-1SUMMARY OF IMAGING MODALITIES FOR EVALUATING THE KIDNEY VASCULATURE ||Download (.pdf) TABLE 44-1 SUMMARY OF IMAGING MODALITIES FOR EVALUATING THE KIDNEY VASCULATURE
|Perfusion Studies to Assess Differential Renal Blood Flow |
|Captopril renography with technetium 99mTc mertiatide (99mTc MAG3) ||Captopril-mediated fall in filtration pressure amplifies differences in renal perfusion ||Normal study excludes renovascular hypertension ||Multiple limitations in patients with advanced atherosclerosis or creatinine >2.0 mg/dL (177 μmol/L) |
|Vascular Studies to Evaluate the Renal Arteries |
|Duplex ultrasonography ||Shows the renal arteries and measures flow velocity as a means of assessing the severity of stenosis ||Inexpensive; widely available ||Heavily dependent on operator’s experience; less useful than invasive angiography for the diagnosis of fibromuscular dysplasia and abnormalities in accessory renal arteries |
|Magnetic resonance angiography ||Shows the renal arteries and perirenal aorta ||Not nephrotoxic, but concerns for gadolinium toxicity exclude use in GFR <30 mL/min/1.73 m2; provides excellent images ||Expensive; gadolinium excluded in renal failure, unable to visualize stented vessels |
|Computed tomographic angiography ||Shows the renal arteries and perirenal aorta ||Provides excellent images; stents do not cause artifacts ||Expensive, moderate volume of contrast required, potentially nephrotoxic |
|Intraarterial angiography ||Shows location and severity of vascular lesion ||Considered “gold standard” for diagnosis of large-vessel disease, usually performed simultaneous with planned intervention ||Expensive, associated hazard of atheroemboli, contrast toxicity, procedure-related complications, e.g., dissection |
TREATMENT Renal Artery Stenosis
While restoring renal blood flow and perfusion seems intuitively beneficial for high-grade occlusive lesions, revascularization procedures also pose hazards and expense. Patients with FMD are commonly younger females with otherwise normal vessels and a long life expectancy. These patients often respond well to percutaneous renal artery angioplasty. If BP can be controlled to goal levels and kidney function remains stable in patients with ARAS, it may be argued that medical therapy with follow-up for disease progression is equally effective. Prospective trials up to now have failed to identify compelling benefits for interventional procedures regarding short-term results of BP and renal function, and long-term studies regarding cardiovascular outcomes, such as stroke, congestive heart failure, myocardial infarction, and end-stage renal failure, are not yet complete. Medical therapy should include blockade of the renin-angiotensin system, attainment of goal BPs, cessation of tobacco, statins, and aspirin. Renal revascularization is now often reserved for patients failing medical therapy or developing additional complications.
Techniques of renal revascularization are improving. With experienced operators, major complications occur in about 9% of cases, including renal artery dissection, capsular perforation, hemorrhage, and occasional atheroembolic disease. Although not common, atheroembolic disease can be catastrophic and accelerate both hypertension and kidney failure, precisely the events that revascularization is intended to prevent. Although renal blood flow usually can be restored by endovascular stenting, recovery of renal function is limited to about 25% of cases, with no change in 50% and some deterioration evident in others. Patients with rapid loss of kidney function, sometimes associated with antihypertensive drug therapy, or with vascular disease affecting the entire functioning kidney mass are more likely to recover function after restoring blood flow. When hypertension is refractory to effective therapy, revascularization offers real benefits. Table 44-2 summarizes currently accepted guidelines for considering renal revascularization.
TABLE 44-2CLINICAL FACTORS FAVORING MEDICAL THERAPY AND REVASCULARIZATION OR SURVEILLANCE FOR RENAL ARTERY STENOSIS ||Download (.pdf) TABLE 44-2 CLINICAL FACTORS FAVORING MEDICAL THERAPY AND REVASCULARIZATION OR SURVEILLANCE FOR RENAL ARTERY STENOSIS
|Factors Favoring Medical Therapy and Revascularization for Renal Artery Stenosis |
Progressive decline in GFR during treatment of systemic hypertension
Failure to achieve adequate blood pressure control with optimal medical therapy (medical failure)
Rapid or recurrent decline in the GFR in association with a reduction in systemic pressure
Decline in the GFR during therapy with ACE inhibitors or ARBs
Recurrent congestive heart failure in a patient in whom the adequacy of left ventricular function does not explain a cause
|Factors Favoring Medical Therapy and Surveillance of Renal Artery Disease |
Controlled blood pressure with stable renal function (e.g., stable renal insufficiency)
Stable renal artery stenosis without progression on surveillance studies (e.g., serial duplex ultrasound)
Very advanced age and/or limited life expectancy
Extensive comorbidity that make revascularization too risky
High risk for or previous experience with atheroembolic disease
Other concomitant renal parenchymal diseases that cause progressive renal dysfunction (e.g., interstitial nephritis, diabetic nephropathy)