1. Renal Artery Stenosis November 12, 2009 Lance D. Dworkin, M.D., and Christopher J. Cooper, M.D. Clinical Practice 2010 년 3 월 23 일 화요일 신장내과 R4 이완수

2. Case Vignette Age/Sex –73/male Chief compliant –shortness of breath  ER visit Personal History –former smoker Past History –Hypertension –Dyslipidemia Vital sign BP 160/75 mmHg HR 60 beats/min RR 24 breaths/min Physical Examination Chest auscultation - diffuse rales Pitting edema (1+) Lab. Serum Creatinine 1.4 mg/dL (eGFR 52ml/min) Urinalysis protein 1+

3. Case Vignette Condition improves after treatment (IV diuretics) But, systolic BP remains elevated (170 mmHg) Magnetic resonance angiography (MRA) –diseased aorta –Lt. renal artery (ostial lesion)  High grade “atherosclerotic stenosis” –Rt. renal artery  normal How should he be further evaluated and treated? Renal artery stenosis (Lt.)

4. Outline The Clinical Problem Strategies and Evidence –Evaluation –Treatment Options Medical Therapy Surgical Therapy Angioplasty and Stenting Areas of Uncertainty Guidelines Conclusions and Recommendations

5. The Clinical Problem “Renal-artery stenosis” Definition –narrowing of one or both renal arteries or their branches. Cause –1. atherosclerosis (most common, 90%) –2. fibromuscular dysplasia (Less frequently) –3. other causes (rare) Vasculitis (Takayasu’s arteritis) Dissection of the renal artery Thromboembolic disease Renal artery aneurysm Renal artery coarctation Extrinsic compression Radiation injury

6. Characteristics of Atherosclerotic Renal-Artery Stenosis and Fibromuscular Dysplasia balloon angioplastycontroversialEffective Tx.?

7. Prevalence –atherosclerotic renal artery stenosis in CKD – 0.5~5.5% –true frequency maybe higher ( ∵ often asymptomatic) Anatomical progression –occur in more than one third of patients –But, one study 5 yrs F/U, “Stenosis”  “Occlusion “ only 3~15% patients treated medically conducted before statin therapy was available Medical treatment is important!!

8. Pathogenesis RAS : renal artery stenosis RBF : renal blood flow

9. Other vascular event? –Renal-artery stenosis (  HTN, CKD)  increased risk for vascular events –Explanation?? Uncertain concomitant atherosclerosis in other vascular beds activation of the renin–angiotensin–aldosterone activation of the sympathetic nervous systems associated renal insufficiency all these factors chronic kidney disease (25%, vs 2%) coronary artery disease (67% vs 25%) stroke (37% vs 12%) peripheral vascular disease (56% vs 13%)

10. Classic clinical clues (renal artery stenosis) 1. onset of stage 2 hypertension (BP >160/100mmHg) after 50yrs old 2. family history of hypertension (-) 3. hypertension associated with renal insufficiency (Esp, RAAS inhibition agent  renal fuction wosens) 4. hypertension with repeated hospital admissions heart failure drug-resistant hypertension (treatment c three drug of different class  BP control fail) Strategies and Evidence

11. Diagnostic Imaging Tests for Renal-Artery Stenosis Once renal-artery stenosis is suspected?? confirmation of the diagnosis??  imaging!! ∵ biochemical tests (plasma renin concentrations)  specificity ↓

12. Duplex Ultrasonography in a Patient with Renal-Artery Stenosis Excellent tool non-invasive no apparent side effects Measurement “renal-artery velocity”  functional assessment of the “severity of stenosis” higher velocity  greater pressure differential across the stenosis Limitation abdominal obesity bowel gas technically demanding (not available at all centers)

13. Magnetic Resonance Angiography Computed Tomographic Angiography High-resolution multislice detector devices Elegant images of the renal arteries and the abdominal aorta Limitation  may affect image quality –equipment –technique –reconstruction of the images –patient-related factors presence of calcium presence of stents ability to hold one's breath during imaging Caution) –CKD patients : toxicity of the contrast medium nephrogenic systemic fibrosis is associated with gadolinium nephropathy is associated with iodinated contrast dye

14. Rt. renal aterty (arrow) 70% ostial stenosis systolic pressure gradient of 28mmHg Lt. renal artery (arrowhead) 40% ostial stenosis pressure gradient of 13mmHg Magnetic Resonance Angiography of the Renal Arteries Showing Severe Bilateral Stenosis

15. Digital subtraction angiography Best image quality, anatomy information use of small-diameter catheters and minimal amounts of contrast material  reduce the risk of vascular complications and contrast nephropathy Limitation –invasive –only in experienced centers –contrast nephropathy in CKD –atheroembolic event –vascular complication at punture site –Radation exposure

16. degree of atherosclerosis of the aorta size of the kidney extent of poststenotic dilatation rapidity of the appearance and washout of contrast material Useful in diagnosis of Renal artery stenosis “Functional significance” of the lesion ? Predict the “response to revascularzation” ? No conclusive test nuclear scintigraphy renin sampling from the renal veins pressure gradients across stenoses Kidney (supplied by an occluded renal artey) is viable? Contributing to hypertension ? Stenosis is affecting intrarenal pressure?

17. Treatment Options Medical Therapy Surgical Therapy Angioplasty and Stenting  improved survival improved BP control less impairment of renal function

18. Medical Therapy Cornerstone of treatment for renal-artery stenosis Recommendations –Multidrug regimens for BP control –RAAS inhibitor is recommended in most patients (Renin–angiotensin–aldosterone system is often activated in patients with renal-artery stenosis) –alpha-blocker or beta-blocker –long-acting CCB –diuretics Caution) “Bilateral severe stenosis“ Use of “RAAS inhibitor”  ARF High-grade stenosis in one kidney Advanced chronic kidney disease  probability of this complication appears to be low in most cases, it is reversible with the discontinuation of treatment

19. Medical Therapy Recent data –ACE inhibitor  reduced risk of death –Statin  reduction in the severity of renal artery stenosis –Statin c stenting  improve survival –Statin, antiplatelet therapy  benefit in patient with atherosclerotic disease

20. Surgical Therapy Surgical revascularization –durable relief of renal-artery stenosis –improves BP control and kidney function Safety –recent data have indicated a 10% in-hospital mortality after this procedure among Medicare patients “balloon angioplasty” vs “surgery” –58 patients with renal-artery stenosis, randomized trial –resulted in similar rates of cure or improvement in HTN, renal function “nonsurgical revascularization”  first-line approach (if an intervention is planned)

21. Angioplasty and Stenting “Fibromuscular dysplasia” –balloon angioplasty remains the preferred form  many patients are able to discontinue all antihypertensive medications –But, medical therapy alone may be appropriate in patients with well-controlled hypertension “Atherosclerotic renal artery stenosis” –balloon angioplasty Less effective Restenosis 71%↑ 3 multicenter trials, without stenting –1 yr follow-up, no significant improvement in BP But, controversial

22. Angioplasty and Stenting Predictors of a favorable outcome of angioplasty –40 years ↓ at diagnosis –duration of hypertension <5 yrs –systolic BP <160 mmHg

23. Angioplasty and Stenting Stents –limit elastic recoil –restenosis-free patency ↑ (compared with angioplasty alone) –BP control ↑after stenting

24. Angioplasty and Stenting Recent trials –1. comparing stenting plus medical therapy with medical therapy alone preservation of renal function no significant benefits with the addition of stenting –2. Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) stent revascularization in addition to medical therapy vs medical therapy alone renal function, mean systolic blood pressure, in rates of renal or cardiovascular events or death no significant difference between the study groups at the 5yrs follow-up

25. Angioplasty and Stenting –3. Stenting in Renal Dysfunction Caused by Atherosclerotic Renal Artery (STAR) trial prevention of loss of kidney function serious procedure-related complications stenting plus medical therapy vs medical therapy alone did not show a benefit

26. Angioplasty and Stenting Revascularization –renin–angiotensin–aldosterone system ↓ –sympathetic nervous system ↓ –possible cardiovascular benefits “pharmacologic therapy”?? directed at these pathways  may have similar benefits  improved survival improved BP control less impairment of renal function

27. Areas of Uncertainty Response to revascularization?  no method reliably predicts Optimal treatment strategy? “Angioplasty and Stenting” vs “medical therapy alone”  remains unclear Data are lacking –randomized clinical trials comparing the effects of various medical regimens Available data from randomized trials –not shown a benefit of “revascularization plus medical therapy” with respect to blood-pressure control and renal function –But, these trials had methodologic limitations, were not powered for the assessment of cardiovascular outcomes, and did not include quality-of-life assessments

28. Previous algorithm

29. Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study –large, multicenter, randomized, controlled trial –funded by the National Institutes of Health –scheduled to be completed in 2011 –medical therapy plus stent revascularization vs medical therapy alone –end point : cardiovascular and renal events –Pending the results of the study best treatment for renal-artery stenosis ? whether to evaluate ?  remain uncertain

30. Guidelines American College of Cardiology–American Heart Association 2005 guidelines (for the care of patients with peripheral-artery disease, including renal-artery stenosis) Revascularization recommendations –class I evidence (i.e., general agreement on usefulness) recurrent congestive heart failure pulmonary edema –class IIa evidence (i.e., conflicting opinions, but with the preponderance of evidence favoring usefulness) global renal ischemia progressive chronic kidney disease unstable angina hypertension that is worsening resistant to medical therapy malignant unexplained unilateral small kidney cannot tolerate antihypertensive medication

31. Conclusions and Recommendations A diagnosis of renal-artery stenosis should be considered in any patient with a history of severe or resistant hypertension, hypertension that is associated with renal insufficiency, or disease in other vascular beds. Clinical Finding Associated with Renal Artery Stenosis Hypertension Abrupt onset of hypertension (age<40)  fibromuscular dysplasia Abrupt onset of hypertension (age>50)  renal artery stenosis Accelerated or malignant hypertension Refractory hypertension (not responsive to therapy c 3≥drugs) Renal abnormalities Unexplained azotemia  renal artery stenosis Azotemia induced by treatment with an angiotensin converting enzyme inhibitor Unilateral small kidney Unexplained hypokalemia Other findings Abdominal bruit, flank bruit, or both Severe retinopathy Carotid, coronary, or peripheral vascular disease Unexplained congestive heart failure or acute pulmonary edema

32. Conclusions and Recommendations Initial examination  measurement of kidney function and a lipid profile Anatomical diagnosis –duplex ultrasonography –CTA or MRA (if high-quality duplex imaging is not available) Therapy –intensive medical therapy –tight BP control with a blocker of the RAAS (serum creatinine and potassium should be closely monitored) –administration of an antiplatelet agent and a statin –Treatment of diabetes and chronic kidney disease Revascularization in the treatment of atherosclerotic renal-artery stenosis ?  controversial