Renal Artery Stenosis and Renal Insufficiency

Weigh individual risks and benefits to determine whether revascularization will improve kidney function.


Ischemic renal disease (or ischemic nephropathy) is defined as a clinically significant decrease in glomerular filtration rates (GFRs) in patients with hemodynamically significant obstruction to renal blood flow.1 The obstruction is typically the result of renal artery stenosis (RAS) of the main renal artery or a dominant branch vessel, although extensive "small vessel" disease can cause similar blockage.

There is controversy among nephrologists and interventionalists (invasive cardiologists, invasive radiologists, and vascular surgeons) regarding the contribution of diminished blood flow by RAS to underperfusion of the kidney and its effect on the development of ischemic nephropathy. Furthermore, these clinicians disagree on whether improving perfusion preserves renal function. Epidemiologic studies suggest that up to 20% of all causes of renal failure in patients over 50 years of age are due to ischemic renal disease.2,3 Once renal vascular disease progresses to renal failure, the 2-year mortality rate has been reported to be 50% or more.4

Medical, endovascular, and open surgical repair have the same management goals in mind: to preserve renal function, control blood pressure, and avoid complications and adverse effects from treatment. Taking into account the increasing age of the US population and the growing awareness of renal vascular disease, clinicians will soon have to decide whether improving renal blood flow in their patients with RAS by means of endovascular techniques or surgery will achieve the goal of improved renal function.

In patients with atherosclerotic RAS and diminished renal function, it is often difficult for physicians to interpret the results from endovascular or open surgical repair. A technically successful revascularization (achieved either through endovascular therapy or surgery) does not always equal a favorable clinical response. Frequently, there is overlap between some degree of existing medical renal disease and renal vascular disease. In addition, in the presence of RAS, the kidney almost always exhibits a certain amount of irreversible nephrosclerosis and atheroembolic disease. With these limitations in mind, uncontrolled clinical studies demonstrate success rates defined as improvement or stabilization in renal function after revascularization in the 55% to 75% range, with approximately 25% to 45% of patients experiencing worsening renal function after revascularization.

The conclusions presented by Dorros et al and Rundback et al are an accurate representation of data from endovascular studies.5,6 Dorros et al demonstrated a strong association between renal function response and baseline renal function. Ninety-five percent of patients with a normal creatinine level showed no worsening of renal function. Five percent of these patients experienced deterioration in renal function at 6 months postprocedure, and poor baseline renal function was associated with decreased survival. Rundback et al showed that clinical benefit was seen in 78% of patients at 6 months, 72% of patients at 1 year, 62% of patients at 2 years, and 54% of patients at 3 years. Patients with better baseline renal function had improved clinical benefit.

In patients treated surgically for ischemic nephropathy, Sherr et al reported that 43% showed improved renal function, 47% had unchanged renal function, and 10% of patients had worsening renal function.7 These investigators also demonstrated improved dialysis-free survival, but only in patients who had improved renal function following surgery. However, as emphasized in the literature, comparison of revascularization results is difficult because patients with renal vascular disease are a mixed population with varied presentations, prognoses, and responses to therapy.8

Randomized, controlled studies evaluating medical therapy alone versus revascularization (either endovascular or surgical) would help guide clinicians regarding revascularization to improve renal function. Currently, three prospective randomized trials have been reported. Unfortunately, these trials primarily compared blood pressure results in patients treated medically versus endovascular revascularization (predominantly angioplasty alone). Two of the trials, the Scottish and New Castle Renal Artery Stenosis Collaborative Group and the Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC), included a small number of patients with renal insufficiency.9,10 However, the results of these trials do not provide any recommendations for the preservation of renal function through endovascular therapy.

In addition to the problem of failure to improve renal function following revascularization, complications associated with revascularization can be significant. A review of 5,865 percutaneous transluminal renal angioplasty and stenting procedures showed a 17.2% rate of complications. The incidence of patients requiring dialysis following revascularization was 0.5%, and there was a 1.3% rate of 30-day mortality.11 In a large surgical series, mortality ranged from 2% to 7%, and there was a 16% to 37% morbidity rate.7,12

Even if large, controlled and randomized trials are performed to compare medical therapy to revascularization (endovascular and surgical) for the treatment of RAS in patients with ischemic nephropathy, clinicians must still weigh the risks versus benefits for each patient individually. Today’s clinician must integrate the clinical, anatomic, and physiologic information from each patient presenting with presumed ischemic nephropathy before deciding to proceed with endovascular therapy. It is important to remember that normal serum creatinine levels can mask severe iatrogenic renal parenchymal damage due to diagnostic and therapeutic intravascular procedures. Fifty percent of total renal mass, or one entire kidney in a patient with two normal kidneys, can be severely damaged without any change in renal function measured by serum creatinine levels. When treating patients with ischemic nephropathy, the risk of further damaging renal function is even higher. In some of these patients, rapid deterioration of renal function can occur with as little as a 10% loss of renal parenchyma.

Clinical evidence of significant RAS includes recent onset of progressive renal dysfunction. Severe or difficult-to-control hypertension and/or recurrent “flush” pulmonary edema may also be present clinically. Diagnosis of RAS typically begins with noninvasive studies. Completed in a technically satisfactory manner, duplex ultrasound and MR angiography can be useful, noninvasive methods for determining the presence of RAS in patients with renal insufficiency. Contrast angiography, however, remains the gold standard for confirming RAS. Because contrast angiography is invasive and can be associated with complications (including contrast nephrotoxicity due to iodinated contrast material in patients with abnormal renal function), care must be taken in performing this test. To reduce these complications, it is important to limit the amount of iodinated contrast material, use alternative contrast agents (such as CO2 and gadolinium) or potentially renal-protective agents (such as fenoldopam and acetylcysteine). In addition, limit and simplify manipulations in the abdominal aorta and renal arteries to reduce cholesterol embolization (Figures 1 and 2).

The amount of stenosis that causes significant renal artery obstruction leading to ischemic nephropathy is unclear. Data suggest that global ischemia (defined as bilateral RAS, or RAS to a single, functioning kidney or dominant kidney) is necessary to produce ischemic nephropathy.13,14 Animal research shows that a 40% reduction in renal perfusion pressure requires a 75% to 95% constriction of the renal artery.15 In patients with bilateral high-grade RAS, reducing systemic arterial pressure using a nitropruside infusion produced abrupt declines in renal blood flow and GFR.16 Performing the same experiment after revascularizing one kidney demonstrated that pressures could be lowered to the same degree without compromising either blood flow or GFR. These patients initially had critical levels of stenosis, at which point perfusion on the kidney depended on the elevated systemic arterial pressure.

Researchers measured the degree of RAS leading to activation of the renin-angiotensin system, in an attempt to determine critical RAS.17 In an experiment involving 49 hypertensive patients with normal renal function, unilateral or bilateral hypersecretion of renin was associated with an 80% or greater reduction in renal artery lumen diameter.

Unfortunately, determining the degree of stenosis from an angiogram is not always reliable. Variability in measuring degrees of stenosis on angiograms has been well documented in the interpretation of coronary angiograms. Measurements of intra- and interobserver variability18-20 demonstrated that accuracy and reproducibility of angiographic estimation of coronary artery stenosis ranges from 58% to 93%. Interpretation of RAS from renal angiograms is not much better.21 In one study, three independent, experienced radiologists assessed 50 renal angiograms (100 renal arteries) twice.22 There was 86% and 92% intraobserver agreement, but interobserver agreement was only 74% and 77%. Interestingly (and fortunately), as the degree of stenosis increased in this study, the degree of agreement among the readers increased as well.

Some interventionalists feel that the lack of agreement concerning angiogram interpretation should encourage more objective methods of analysis such as quantitative computer techniques. However, eccentric lesions, motion, overlying vessels, and poststenotic dilatation are only a few of the problems encountered when using automated, edge-detection algorithms to measure RAS. Some experts advise that great care must be taken when crossing an RAS, lest access be lost. Other interventionalists have promoted the use of intra-arterial pressure gradients across an identified RAS as a physiologic test to ascribe significance to the degree of anatomic stenosis measured on a renal angiogram. This recommendation is due (at least in part) to the fact that providing physiologic evidence that the degree of stenosis is significant in patients who display clinical and anatomic evidence of RAS and who also have ischemic nephropathy can be difficult. Although radionuclide scans and plasma renin activity studies can be useful methods to prove physiologic significance of RAS in patients with normal renal function, these studies are less reliable in patients with renal insufficiency.23,24

In a study by Gross et al, a pressure gradient wire system was used to measure pressure gradients across angiographically documented RAS.25 The investigators were able to show a correlation between the resting gradient and stenosis severity, and renal function and systemic blood pressure. Gross et al found that a 50% diameter stenosis correlated with a 22-mm Hg peak-to-peak systolic gradient. They constructed a graph to estimate pressure gradients for different degrees of stenosis. In their model, a 70% diameter stenosis correlates with approximately a 50-mm Hg peak-to-peak systolic pressure gradient, and an 80% diameter stenosis correlates with approximately an 80-mm Hg peak-to-peak systolic pressure gradient. In this model, stenoses greater than 70% in diameter are clearly associated with a rapid rise in pressure gradients.

Which patients with ischemic nephropathy and RAS should be offered treatment with endovascular therapy? Patients with mild-to-moderate renal dysfunction and global ischemia, with RAS defined as stenosis of at least 70% to 80%, should be considered reasonable candidates for endovascular treatment. In patients with angiographic evidence of RAS in the 50% to 70% range, the degree of hemodynamic significance of these lesions should be confirmed with pressure measurements that identify peak-to-peak systolic pressure gradients approaching 50 mm Hg. Although the results of randomized, controlled studies evaluating medical treatment versus endovascular therapy for patients with ischemic nephropathy due to RAS might help simplify the decision-making process, the potential risks and benefits for each patient must still be balanced.

David J. Spinosa, MD, is Associate Professor of Radiology in the Division of Angiography and Interventional Radiology at the University of Virginia Health System in Charlottesville, Virginia. Dr. Spinosa may be reached at (434) 924-9401;

Kenneth Rosenfield, MD, is Director of Cardiac and Vascular Services in the Cardiology Division at Massachusetts General Hospital in Boston, Massachusetts. Dr. Rosenfield may be reached at (617) 724-1935;

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Endovascular Today is a publication dedicated to bringing you comprehensive coverage of all the latest technology, techniques, and developments in the endovascular field. Our Editorial Advisory Board is composed of the top endovascular specialists, including interventional cardiologists, interventional radiologists, vascular surgeons, neurologists, and vascular medicine practitioners, and our publication is read by an audience of more than 22,000 members of the endovascular community.