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CLINICIAN'S CORNER
An 82-Year-Old Woman With Worsening HypertensionReview of Renal Artery Stenosis
Kenneth Rosenfield, MD;
Michael R. Jaff, DO
JAMA. 2008;300(17):2036-2044.
ABSTRACT
Renal artery stenosis (RAS) is a common disorder in adults with atherosclerosis and is associated with hypertension, impaired renal function, congestive heart failure, and angina pectoris. The incidence of RAS is increasing because of the aging of the US population and increasing prevalence of atherosclerosis. The case of Mrs S, an 82-year-old woman with long-standing hypertension and unilateral RAS detected by magnetic resonance angiography, illustrates the challenges surrounding indications for revascularization. The discussion reviews the clinical presentation and natural history of RAS and strategies for diagnosis. The role of medical therapy, surgery, and endovascular therapy are reviewed, particularly in the context of guidelines and systematic reviews to help clinicians and patients facing this challenging decision.
INTRODUCTION
DR SHIP: Mrs S is an 82-year-old woman with hypertension, hyperlipidemia, and renal artery stenosis (RAS) who reports a long history of feeling generally unwell—tired, achy, and just "not right." She had been a dancer and subsequently attended law school. She has 5 healthy adult children and now lives alone. She does not smoke or drink alcohol and exercises 3 times weekly. She has Medicare and AARP insurance.
Mrs S worried for quite a while that her feeling unwell was attributable to her elevated cholesterol level. She was evaluated by 2 cardiologists, who differed in their recommendations regarding the need for catheterization. At age 80 years, she chose to undergo a total body computed tomography (CT) scan, at an out-of-pocket cost of approximately $900, because of these conflicting recommendations. She had a high calcium score (432), which was suggestive of a high atherosclerotic plaque burden in the region of her left anterior descending artery. Because of this, she was referred by the radiologist to a third cardiologist.
At the time of her third cardiology visit, Mrs S reported a medical history of hypercholesterolemia and hypertension, which was not well controlled. Her antihypertensive medications at that time were atenolol, 50 mg/d, and methyldopa, 500 mg twice daily. She denied chest pain or dyspnea on exertion. Her blood pressure was 180/80 mm Hg bilaterally. Her cardiovascular examination results were normal without murmurs. A soft central systolic abdominal bruit, radiating to both flank regions, was appreciated. A gadolinium-enhanced magnetic resonance angiogram (MRA) of the renal arteries was obtained because of a concern about possible RAS, and a stress test was also performed. Her antihypertensive regimen was changed to atenolol, 50 mg/d, and ramipril, 5 mg/d. However, she developed a cough while taking ramipril and switched to extended-release nifedipine, 30 mg/d. With this regimen her blood pressure was well controlled at 138/78 mm Hg. Her surgical history is notable for a cholecystectomy and oophorectomy.
During the stress test she had nonanginal symptoms. She had no electrocardiographic changes at stage III of a Bruce protocol and 101% of her maximum heart rate. Her MRA (Figure) showed severe stenosis at the origin of the main left renal artery with a patent accessory renal artery to the lower pole of the left kidney. There was no stenosis of the right renal artery. Both kidneys were normal size, with symmetric excretion of contrast. A decision was made at that point not to intervene on the RAS because of its location.
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Figure. Magnetic Resonance Angiogram (MRA) of Mrs S’s Renal Arteries
MRA showing severe stenosis at the origin of the main left renal artery (arrowhead) with a patent accessory renal artery to the lower pole of the left kidney. Both kidneys are normal size, with symmetric excretion of contrast.
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Her blood pressure has been difficult to control because she has had adverse effects or been intolerant to many agents, including lower extremity edema with a calcium channel blocker as well as cough in response to ramipril. Her current antihypertensive regimen includes combination atenolol-chlorthalidone, 50/25 mg, 1 tablet daily, and felodipine, 2.5 mg at night. Other medications include aspirin, 81 mg/d, fluvastatin, 80 mg/d, omeprazole, 20 mg/d, nabumetone, 500 mg twice daily, vitamin D, 400 IU/d, calcium, 950 mg/d, and a multivitamin. With this regimen she has felt well and her blood pressure is reasonably well controlled (140/80 mm Hg).
Her recent complete blood cell count, electrolytes, and renal function test results were normal (creatinine, 0.8 mg/dL [70.72 µmol/L]). Her total cholesterol is 202 mg/dL (5.23 mmol/L); high-density lipoprotein (HDL), 56 mg/dL (1.45 mmol/L); total/HDL cholesterol ratio, 3.6; low-density lipoprotein, 104 mg/dL (2.69 mmol/L); and triglycerides, 209 mg/dL (2.36 mmol/L).
MRS S: HER VIEW
I didn't have any medical problems until 1980. I had a gallbladder removed. And then I found out that I had high blood pressure. So I’ve been going to doctors for the high blood pressure since.
Sometime along the way, I started to feel very poorly. And I kept complaining and going back and complaining and complaining. I asked for MRIs [magnetic resonance imaging]; that's how poorly I was feeling. And towards the end I wasn't able to climb stairs at all or to walk a block. I was really feeling like I was going to have a stroke or just drop dead someplace.
I went to a private clinic and paid to have a CT of the whole body. They told me that I had plaque and that I should see a cardiologist because it was through my whole body. I have cholesterol deposits in 3 arteries in my heart, the artery to my stomach, and the arteries to the kidneys. They did x-ray my neck and said it was all right.
I would like to know whether or not I should have a procedure for the renal artery stenosis now or at any time in the future. What are my chances of having a successful procedure if the plaque is so near the aorta and what are my risks in having the procedure in an emergency?
AT THE CROSSROADS: QUESTIONS FOR DRS JAFF AND ROSENFIELD
What is the incidence and prevalence of RAS? What are the clinical and laboratory findings that should engender a search for RAS? What is the best approach to imaging? What is the natural history of untreated RAS? What are the options and indications for treatment? What is known about the potential risks and benefits of each? What does the future hold? What do you recommend for Mrs S?
DRS ROSENFIELD AND JAFF: This 82-year-old woman is at a crossroads that represents one of the greatest challenges in vascular medicine today: whether to treat RAS and under what circumstances. She has a long-standing history of poorly controlled hypertension, initially treated with a suboptimal regimen of a β-blocker and  -methyldopa. Her systolic blood pressure was elevated at 180 mm Hg. She reported a general sense of not feeling well and had lost the ability to climb stairs or walk without extreme fatigue. Her symptoms were out of proportion to what one would expect from deconditioning alone. While unlikely to be directly attributable to hypertension, her fatigue could represent intolerance to her antihypertensive medications or could be a manifestation of myocardial ischemia, left ventricular hypertrophy and associated diastolic dysfunction, or hypertrophic cardiomyopathy. Her leg fatigue could represent intermittent claudication due to peripheral artery disease.
Because of her "high plaque burden," she underwent an evaluation for a common secondary etiology of hypertension. She was found to have left RAS with a patent accessory left renal artery and patent right renal artery. She and her physicians are now faced with a common dilemma: after optimization of her medical regimen, what are the advantages and risks of revascularization of her left RAS?
Prevalence of RAS
The prevalence of RAS in the general population is small. Among patients diagnosed as having hypertension, RAS occurs in 1% to 6%.1 However, in selected patient populations, such as those undergoing diagnostic coronary arteriography, the prevalence increases to greater than 20%. In a cohort of 297 hypertensive patients referred for coronary arteriography who also underwent abdominal aortography during the same procedure, 28% had RAS with less than 50% narrowing and 19.2% were found to have RAS with at least 50% narrowing.2
Particularly relevant to Mrs S, in a study of patients aged 65 years or older participating in the Cardiovascular Health Study, renal artery duplex ultrasonography was performed sequentially in 870 patients, and 6.8% were found to have RAS. In this cohort, RAS was associated with a significant increase in adverse coronary events, including hospitalization for angina pectoris; fatal or nonfatal myocardial infarction; and need for coronary revascularization.3 Conlon et al4 followed up patients with RAS detected at the time of coronary angiography. The 4-year survival rate was 65% in patients with renal artery disease vs 86% in patients undergoing coronary arteriography without RAS.
Clinical and Laboratory Findings
Renal artery stenosis is one of the most common secondary causes of hypertension in the adult population, especially among those with other risk factors for development of atherosclerosis.5 The clinical clues that suggest a new diagnosis of RAS include new onset of hypertension after age 55 years, hypertension that is refractory or resistant to medical therapy, acceleration of previously well-controlled hypertension, development of azotemia during treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), asymmetric renal size, and presence of hypertension in patients with concurrent atherosclerosis elsewhere (eg, coronary, carotid, peripheral arterial), among others (Box).6 Mrs S has several of these factors, including the age at which her hypertension worsened, difficult-to-control hypertension on an antihypertensive regimen, and presence of multivessel coronary artery disease on CT scan.
| Box. Clinical Clues Suggestive of Renal Artery Stenosis6
- New onset of diastolic hypertension prior to age 35 years or after age 55 years
- Failure to adequately control hypertension with maximal doses of 3 antihypertensive agents with appropriate synergy
- Sudden deterioration in previously well-controlled hypertension
- Any episode of malignant hypertension
- Azotemia after therapy with an angiotensin-converting enzyme inhibitor
- Discrepancy in renal size found on ultrasonography, computed tomography, or magnetic resonance imaging
- Hypertension and papilledema
- Presence of hypertension and aortoiliac atherosclerosis, abdominal aortic aneurysm, or infrainguinal peripheral arterial disease
- Presence of hypertension and unexplained azotemia
- Presence of hypertension and multivessel coronary artery disease
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Laboratory studies are neither specific nor sensitive for the diagnosis of RAS. However, laboratory measurement of renal function, serum potassium levels, acid-base status, and urinalysis should be performed to exclude other potential secondary etiologies of hypertension.7 Mrs S reported that her blood pressure has been suboptimally controlled for years, and she has generalized atherosclerosis. In such a patient, the possibility of RAS should always be considered.
Diagnosis of RAS
Once clinical suspicion is present, several noninvasive diagnostic modes, including renal artery duplex ultrasonography,8 MRA,9 and CT angiography,10 can provide information to confirm or eliminate the diagnosis of RAS. These diagnostic techniques require specific equipment, skilled technologists, and physicians trained to interpret the findings, and their accuracy is in part a function of these factors. Duplex ultrasonography is the least expensive of these modes but requires the greatest training by the technologist and interpreting physician.
Mrs S’s MRA revealed a patent right renal artery, severe ostial stenosis of the left renal artery, and a patent polar (accessory) renal artery. In some series, MRA has been shown to be quite sensitive (>90%) in detecting RAS. Unfortunately, a major limitation of MRA is overestimation of moderate stenoses as severe (eg, lack of specificity).11 In addition, gadolinium administration during MRA, particularly in patients with preexisting azotemia, has been associated with a severe, debilitating, and deadly disorder, nephrogenic systemic fibrosis.12 Duplex ultrasonography would be particularly helpful here because it would assess the true hemodynamic significance of the left RAS, as well as pole-to-pole renal length, renal cortical thickness, and the renal resistive index. In 1 series, a renal resistive index of less than 0.8 predicted a significant and durable reduction in mean arterial blood pressure and stabilization of renal function after renal artery revascularization.13 Given that renal artery duplex ultrasonography is noninvasive and cost-effective,14 we would pursue this test for Mrs S before making any decision regarding invasive therapy.
Natural History of Untreated RAS
Like atherosclerosis in other vascular beds, RAS is a progressive disorder. In a pooled review of 5 trials with serial arteriography,15 49% of the renal arteries demonstrated progression of stenosis during follow-up ranging from 6 to 180 months. Fourteen percent of these vessels progressed to occlusion. In a prospective natural history study,16 serial renal artery duplex ultrasonography was performed in 84 patients with at least 1 abnormal renal artery whose therapy did not involve revascularization. During a mean follow-up of approximately 13 months, the progression of RAS in 139 renal arteries studied was 42%. The occlusion rate at 2 years was 11%. The overall progression rate was 20%.
Although it is evident that progression of RAS occurs commonly, it is more important to note the ominous association among RAS, cardiovascular events, and mortality. The 15-year survival of patients with end-stage renal disease because of RAS was 0% compared with 32% in patients committed to dialysis because of other causes (eg, polycystic kidney disease). In a prospective angiographic trial,17 RAS was the cause of end-stage renal disease in 14% of new patients beginning dialysis.
What Are the Options for Treatment?
Options for therapy in atherosclerotic RAS include optimal medical therapy alone or optimal medical therapy in combination with either endovascular or surgical revascularization. Mrs S faces a difficult decision. She has unilateral RAS with apparently well-preserved renal function and size. After changing antihypertensive medications, she has better blood pressure control and currently feels better, at least for the time being, than she did in the past. The pros and cons of all treatment options must be considered prior to a decision about revascularization.
Cardiovascular risk reduction therapy is essential as part of the management strategy for patients with RAS. A review of RAS treatment by the Agency for Healthcare Research and Quality18 found no randomized trials directly comparing aggressive medical therapy with angioplasty and stent placement and concluded that there is insufficient evidence to suggest a clear advantage of renal revascularization over maximal medical therapy.
The American College of Cardiology/American Heart Association (ACC/AHA) peripheral arterial disease guidelines19 suggest the following class I (evidence for or general agreement that treatment is beneficial, useful, and effective) level of evidence (LOE) B (based on a single randomized trial or nonrandomized study) indication for intervention in RAS: reduction in incidence of recurrent unexplained congestive heart failure or sudden unexplained pulmonary edema to which the RAS is thought to be contributing. There are 3 class IIa (weight of evidence favors usefulness/efficacy) LOE B recommendations: (1) treatment for accelerated, resistant, malignant hypertension, hypertension with a unilateral small kidney, or hypertension with medication intolerance; (2) chronic renal insufficiency with bilateral RAS or stenosis of the renal artery supplying a solitary functioning kidney; and (3) unstable angina likely due to RAS (global renal ischemia). The remaining clinical scenarios of asymptomatic bilateral/solitary RAS, asymptomatic unilateral RAS with a viable kidney, and unilateral RAS with chronic renal insufficiency and a normal contralateral renal artery and kidney have class IIb (usefulness/efficacy less well established) LOE C (based on consensus opinion, case studies, or standard of care) recommendations.
Medical Therapy. Options for medical therapy of RAS have improved with the development of new antihypertensive medications. In the 1970s, 32% of patients with severe hypertension were found to have RAS,20 but first-generation antihypertensive therapy provided adequate control in less than 50% of these patients.21 The added options of ACE inhibitors, ARBs, and calcium channel antagonists have contributed to more than 80% of patients in several series having excellent blood pressure control.22 Optimizing Mrs S’s antihypertensive regimen and then reassessing the level of blood pressure control seems a reasonable initial approach for her.
Mrs S is currently taking a β-blocker and a diuretic, appropriate first-line therapies as suggested by recommendations of the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.7 Thiazide diuretics are particularly helpful in elderly patients with systolic hypertension and are generally very well tolerated.23 Mrs S is also taking felodipine, a calcium channel antagonist. Felodipine could be replaced by an ARB because ARBs are an effective class of antihypertensive agent in patients with RAS.24 The ACC/AHA guidelines provide LOE A (evidence from multiple randomized trials or meta-analyses) for the use of ACE inhibitors, β-blockers, and calcium channel blockers. Angiotensin II receptor blockers received an LOE B rating for use in patients with hypertension and RAS. Patients with bilateral RAS are at risk of precipitation of renal dysfunction when treated with ACE inhibitors or ARBs;, these patients therefore require close monitoring of renal function during initiation of treatment.24
Surgical Revascularization. Surgical revascularization techniques have improved greatly over the years, although renal artery bypass continues to be associated with significant morbidity and mortality. In a series of 323 surgical renal artery revascularization procedures performed over 15 years,25 the overall mortality rate from the procedure was 5.6%. In surgical cases that avoided the aorta, the mortality rate was 4.1% vs 8.1% for those with grafts arising from the aorta. Major postoperative complications occurred in 5.9% of patients with aortorenal bypass alone and in 21.4% of patients with combined aortic replacement and aortorenal bypass. Early (<30-day) graft failure occurred in 2.1% of combined procedures and 17.6% of isolated aortorenal bypass cases.
A retrospective case series describing the clinical outcomes of revascularization at a single institution from 1987 to 1998 reported on 290 procedures in 232 hypertensive patients with atherosclerotic renal disease and preoperative serum creatinine levels of 1.8 mg/dL (159 µmol/L) or more. There were 17 postoperative deaths (7.3%) within 30 days of surgery, and 58% of survivors had improved renal function (at least 20% improvement in estimated glomerular filtration rate [GFR]), including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%.26 Hypertension resolved in 21% and improved in 70% of survivors.
Due to her age and generalized atherosclerosis, Mrs S would be at risk of serious perioperative major adverse events (eg, myocardial infarction, stroke) and a mortality rate of up to 8% at 30 days following surgery. Given that her RAS is unilateral and she has stable renal function, she more likely would be harmed than helped by surgical revascularization.
Endovascular Renal Revascularization. The first case series of percutaneous transluminal balloon angioplasty (PTA) for RAS was published in 1983.27 Of the patients reported on, angioplasty was technically successful (complete resolution of the stenosis with absence of residual translesional pressure gradient or flow-limiting dissection) in 87% of the 31 with fibromuscular dysplasia and 57% of the 51 with unilateral stenosis due to atherosclerosis. Either cure or improvement in hypertension was seen in 93% of fibromuscular dysplasia and 84% of atherosclerotic patients at 16 months' mean follow-up. Follow-up angiograms performed in 15 of the patients with atherosclerosis demonstrated persistent relief of stenosis at a mean of 22 months.
A subsequent case series in 100 consecutive patients with 125 renal artery stenoses28 reported technical success in 67.7% of solitary kidneys and 76.2% of unilateral renal artery revascularizations. During a mean follow-up of 29 months, hypertension was cured or reduced in 59% of patients. Patients with ostial RAS had the least benefit in blood pressure control (32.5%). Complications resulting from PTA occurred in 14% of patients, with deaths in 2 patients and acute renal insufficiency in 26% of patients after PTA. As noted above, restenosis after renal PTA occurred in more than 50% of cases.
Atherosclerotic RAS typically involves the ostium, and the stenosis is thought to be caused by aortic plaque that drapes over the ostium and extends into the proximal vessel. This explains the severe recoil seen after balloon angioplasty alone and is the reason that a stent with sufficient radial force is required to provide a scaffold to maintain luminal patency.
In a case series of 100 patients with 133 renal arteries, stent deployment was technically successful in 99% of cases,29 with hypertension cured or improved in 76% of patients 6 months after the procedure. Restenosis occurred in 19% of cases at a mean follow-up of 8.7 months. No patient died as a result of the procedure and 2 patients had contrast-induced acute renal failure, neither requiring dialysis.
A multicenter prospective series30 evaluating renal artery stent deployment after failed PTA demonstrated a systolic blood pressure reduction of 19 mm Hg in 158 patients followed up at 24 months. Mean creatinine level was 1.36 (120 µmol/L) at baseline and 1.46 mg/dL (129 µmol/L) at 24 months, representing relative stabilization of renal function during the same period. Nearly 20% of patients had major adverse events, including the need for repeat intervention in 14.4% of patients. In-stent restenosis occurred in 17.4% at 9 months.
The Table shows published studies of renal artery stent revascularization.31-33,35, 44-52 Other publications have summarized the impact of stent revascularization on control of hypertension and renal function.44
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Table. Results of Case Series of Renal Artery Stent Revascularization
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Medical Therapy vs Revascularization. Few randomized controlled trials have compared medical therapy with revascularization, the most important information Mrs S’ treatment decision requires. In the DRASTIC (Dutch Renal Artery Stenosis Intervention Cooperative) trial, 106 patients with RAS and hypertension (diastolic blood pressure  95 mm Hg despite 2 effective antihypertensive drugs) were randomized to receive either antihypertensive drug therapy alone or PTA.45 The authors concluded that PTA, with or without the use of stents, offered no advantage over drug therapy, but the study was marred by numerous methodological issues, including insufficient numbers of patients enrolled to detect a difference between groups, crossover of 22 of 50 patients (44%) from their randomized medical therapy group to PTA because of inability to control their blood pressure by medical therapy alone, and only 2 patients receiving stents. However, patients who were randomized to PTA required fewer antihypertensive medications to control blood pressure (P < .001) and, after 12 months of follow-up, fewer patients in the PTA group had worsened blood pressure.
Given the limited data on which to base Mrs S’ treatment decision, her possible benefits and risks should be considered. Mrs S was concerned about generally feeling poorly and having difficulty walking or stair climbing. These symptoms could represent angina pectoris due to coronary ischemia, intermittent claudication due to peripheral artery disease, or perhaps simply medication intolerance. If these symptoms persisted after her medications were adjusted, they could represent coronary ischemia or a class IIa (weight of evidence/opinion in favor of usefulness/efficacy) recommendation for intervention for her unilateral RAS. However, since her symptoms improved with medication adjustment and control of her hypertension, current evidence does not suggest revascularization based on stenosis alone.
What Does the Future Hold?
Two large randomized trials, the CORAL (Cardiovascular Outcomes in Renal Artery Lesions) trial (http://www.coralclinicaltrial.org/)42 and the ASTRAL (Angioplasty and Stent for Renal Artery Lesions) trial (http://www.astral.bham.ac.uk/), are expected to inform the debate on revascularization vs medical therapy. Until then, decisions must be based on available data, clinical experience, and patient preference.
Brain-type natriuretic peptide (BNP) was shown in 1 study to predict improvement in blood pressure control after renal artery stent revascularization.46 In 27 patients with refractory hypertension and RAS, 77% of those with baseline BNP levels higher than 80 pg/mL had improved blood pressure control after revascularization, while none of the patients with BNP levels of 80 pg/mL or lower had similar blood pressure responses. If these data are reproduced in larger series, they could provide a helpful predictor of response for clinical decision making.
Attempts to lessen complications related to renal artery stent revascularization have focused on prevention of in-stent restenosis and periprocedural atheromatous emboli (occurring in up to 20% and 10% of patients, respectively). A prospective multicenter study compared restenosis after deploying bare metal vs sirolimus-eluting stents in RAS and found no difference in arteriographic patency at 6 months.47 Embolic debris have been implicated in renal failure after revascularization, and one preliminary retrospective case series in 37 patients48 found a rate of renal deterioration of 5% after use of embolic protective devices such as those used in carotid endovascular intervention and intervention in coronary saphenous vein grafts during the procedure. A 2 x 2 factorial design randomized trial of use of embolic protection devices and glycoprotein IIb/IIIa inhibition in 100 patients demonstrated that combination embolic protection and platelet inhibition, but neither intervention alone, preserved postintervention estimated glomerular filtration rate.49 Currently, though, neither drug-eluting stents nor customized embolic protection devices designed for the renal artery are available, and evidence does not support the incremental benefit with these modifications of renal artery intervention.
RECOMMENDATIONS FOR MRS S
DR JAFF: I do not think that Mrs S meets indications for renal artery endovascular revascularization. Although she is currently taking 3 antihypertensive agents for control of her blood pressure, she is not at maximal doses of her β-blocker or calcium channel antagonist.
I would recommend additional studies to better define the cardiovascular consequences of her hypertension, including 2-dimensional echocardiography to determine her systolic function, the presence of left ventricular hypertrophy and impaired diastolic relaxation of the left ventricle, and 24-hour ambulatory blood pressure monitoring or home self-measurement of blood pressure, as these values tend to correlate with target organ damage better than office blood pressures.50 Renal artery duplex ultrasonography could help determine the hemodynamic significance of the left RAS, renal size, cortical thickness, and renal resistive index. If her blood pressure is suboptimally controlled, I would consider beginning an ARB in place of a calcium channel antagonist. Increasing her dose of atenolol, if tolerated, would be reasonable as well. If her blood pressure remains difficult to control despite maximal doses of atenolol, chlorthalidone, and an ARB, and the renal artery duplex ultrasound examination demonstrates a significant left RAS, then I would consider renal artery stent revascularization.
DR ROSENFIELD: Mrs S is not unlike many patients referred to me with a diagnosis of RAS, either detected incidentally or as part of a systematic evaluation for refractory hypertension, with or without renal insufficiency. Such patients, who have had hypertension for many years, sometimes enter into an "accelerated phase," wherein the blood pressure is increasingly difficult to manage. In such patients, one may infer that RAS has likely been present for some time but now has progressed to the point of hemodynamic significance. I agree with Dr Jaff's approach; that is, before considering revascularization therapy for Mrs S, we should confirm the hemodynamic significance of the left renal artery lesion and estimate its relative contribution to her hypertension.
However, before considering what if anything to do with the renal artery, we should make certain that Mrs S’s other symptoms—her sense of feeling poorly, generalized fatigue, and inability to climb stairs or walk—are not a manifestation of significant obstructive coronary artery disease. Based on the high calcium score from her electron beam CT scan, Mrs S has evidence of coronary plaque. One certainly could make a case for pursuing further noninvasive—and possibly invasive—cardiac evaluation.
If her blood pressure is difficult to control, then the degree of stenosis is important. If Mrs S’s renal stenosis is less than 50%, or even 60%, without a significant pressure gradient across the lesion, then it is less likely to be contributing to her hypertension and it should be monitored but not revascularized at this time. To assess her hypertension, I would rely on home and office measurements to confirm her apparently good blood pressure control.
A few additional factors may influence the potential benefit vs risks of revascularization for Mrs S. For example, findings on MRA or CT angiography suggesting the presence of friable plaque in her aorta or an aortic aneurysm lined with thrombus would increase the likelihood of a revascularization-related complication due to atherosclerotic debris or adherent thrombus and, thus, the threshold for renal intervention. The size and caliber of the renal artery also affect outcome: smaller-diameter (<4 mm) renal arteries are more likely to develop restenosis.51
CONCLUSION
Mrs S must first understand the importance of the finding of RAS and the implications with respect to her overall cardiovascular health. First, given that RAS is a marker for atherosclerosis in other vascular territories, she should receive aggressive treatment with lipid-lowering agents and aspirin, and pharmacologic management of her blood pressure to achieve consistent control (<140/80 mm Hg) to reduce her risk of heart attack and stroke. Second, although she has a stenosis, she must know that no clear indication for revascularization exists. Her medical regimen should be adjusted to find agents that are tolerable and do not result in fatigue. Renal revascularization should be considered only if her blood pressure is not controlled with medical therapy, if she cannot tolerate (eg, has extreme fatigue or otherwise) medications required to achieve control, or if her renal function deteriorates. Should she ultimately undergo intervention, even successful revascularization does not obviate the need for continued adjustment of antihypertensive medications and aggressive treatment of risk factors to achieve long-term reduction in cardiovascular morbidity and mortality. Finally, as mentioned earlier, although her symptoms of feeling poorly and inability to walk may represent medication intolerance, further investigation into alternative etiologies should be considered.
QUESTIONS AND DISCUSSION
A PHYSICIAN: Is there a role for aggressive cholesterol management with statins in RAS?
DR JAFF: This is the classic example of extrapolating data from other vascular beds. There has not been a trial looking at the impact of statins in renal artery atherosclerosis, looking at either delay in progression or induction of regression, and I doubt that there ever will be.
However, given that many of these patients have concomitant coronary atherosclerosis, and we know the impact of statin therapy on reduction in major cardiovascular events and mortality, we need to extrapolate that statin therapy should be initiated in patients with renal artery atherosclerosis. The recent Adult Treatment Panel III/National Cholesterol Education Program52 consensus conference guidelines list atherosclerotic peripheral arterial disease as a coronary equivalent for statin therapy. In our practice, we recommend aggressive lipid lowering for these patients.
A PHYSICIAN: Is there a GFR below which you would recommend against intervention?
DR ROSENFIELD: There probably is not a lower limit for GFR below which intervention is contraindicated. In fact, patients who have a lower GFR sometimes demonstrate the best response to revascularization.53 I have had a number of patients recently committed to dialysis in whom renal function has been restored by reperfusing the kidney. That said, risk is increased when performing the intervention in a patient with borderline renal function, although a patient with a normal GFR could end up with a low GFR if one is not careful.
DR JAFF: A patient with low GFR is the classic scenario of high risk/high benefit. In someone who has advanced renal dysfunction due to global renal ischemia and is basically teetering on the precipice of dialysis, the risk of the procedure is absolutely evident. However, the risk of not doing the procedure is having the patient end up on dialysis solely because of renal artery disease. Once dependent on dialysis, the patient's lifestyle and longevity are terribly compromised. Thus, if you can minimize atheroembolic risk and contrast load, proceeding with an intervention is responsible and appropriate.
DR ROSENFIELD: It is critical to understand the etiology of renal dysfunction in a given patient. In a patient with severe unilateral stenosis (with a patent vessel to the other side), RAS may cause hypertension and contribute to the renal dysfunction. However, RAS in such cases is not the main reason for azotemia, and revascularization would not be expected to restore renal function. In contrast, patients with "global renal ischemia" (compromised blood flow to entire functioning kidney mass) tend to derive the most dramatic benefit from renal revascularization, especially in terms of restoring or preserving renal function.54
AUTHOR INFORMATION
Corresponding Author: Kenneth Rosenfield, MD, Section Head, Vascular Medicine and Intervention, Division of Cardiology, Massachusetts General Hospital, 55 Fruit St, GRB 800, Boston, MA 02114 (krosenfield{at}fastmail.us).
Financial Disclosures: Dr Rosenfield reports that he has received research and educational grants at Massachusetts General Hospital from Abbott Vascular, BARD, Baxter, Boston Scientific, Cordis Endovascular, EV3, Invatec, and Lumen Biomedical; has served as a consultant to Abbott Vascular, BARD, Baxter, Boston Scientific, Cordis Endovascular, EV3, Angioguard, Lumen Biomedical, Medicines Company, Xtent, CardioMind, Medical Simulation Corporation, and Medical Ventures/B-Balloon; and has equity interest/royalties/stock options in Angioguard (Cordis), CardioMind, Medical Simulation Corporation, Xtent, CardioMEMS, and Lumen Biomedical. Dr Jaff reports that he has served as a consultant to Abbott Vascular, Boston Scientific (noncompensated), Cordis Endovascular (noncompensated), Medtronic Vascular (noncompensated), and Paragon IP and has equity interest in Square One Inc.
Funding/Support: This Clinical Crossroads was made possible by a grant from the Sidney R. Rabb Charitable Trust and the Sidney and Esther Rabb Charitable Foundation.
Role of the Sponsors: The funding organization did not participate in the collection, management, analysis, and interpretation of the data or preparation, review, or approval of the manuscript.
Additional Contributions: We thank the patient for sharing her story and for providing permission to publish it. We, the authors, thank Amy Ship, MD, Risa Burns, MD, and Anna Mattson for their contributions to preparing the manuscript.
This conference took place at the Medicine Grand Rounds of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, on March 9, 2006.
Clinical Crossroads at Beth Israel Deaconess Medical Center is produced and edited by Tom Delbanco, MD, Howard Libman, MD, Eileen E. Reynolds, MD, Amy N. Ship, MD, and Anjala V. Tess, MD. Risa B. Burns, MD, is series editor.
Author Affiliations: Dr Rosenfield is Lecturer on Medicine, Harvard Medical School, and Section Head, Vascular Medicine and Intervention, Division of Cardiology, Massachusetts General Hospital, Boston, and Dr Jaff is Associate Professor of Medicine, Harvard Medical School, and Medical Director, Massachusetts General Hospital Vascular Center, Boston.
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